Advertisement

Common Pathways to Neurodegeneration and Co-morbid Depression

  • Darcy Litteljohn
  • Emily Mangano
  • Shawn HayleyEmail author
Chapter

Abstract

Depression is highly co-morbid with a number of neurodegenerative conditions, including Parkinson’s disease (PD), Alzheimer’s disease (AD), stroke and multiple sclerosis. Although psychosocial stress and impairment play a substantial role, accumulating evidence suggests that co-morbid depressive illness may emerge from alterations in processes related to the primary neurodegenerative condition. For instance, depression in PD may occur long before motor disability and in many cases is likely related to early degeneration in brainstem or limbic regions. We posit that pro-inflammatory cytokines and their associated inflammatory signaling pathways (e.g., JAK-STAT, NFκB, and MAP kinases), as well as other immuno-inflammatory factors such as the microglial inducible enzyme, cyclooxygenase-2 (COX-2), may play a primary role in modulating the emergence of co-morbid depression. In this regard, neuroprotective/neurotrophic anti-inflammatory factors may have important antidepressant properties. The present review will cover the evidence concerning the mechanisms through which depression might emerge in PD and other neurodegenerative disorders. Secondly, we will focus on the important cytokines, inflammatory co-factors and intracellular signaling proteins that could be targeted to potentially provide therapeutic benefit for depression as well as the primary neurodegenerative condition.

Keywords

Parkinson’s disease Depression Co-morbidity Inflammation Cytokine Cyclooxygenase 

Abbreviations

5-HT

5-hydroxytryptamine (serotonin)

5-HTTLPR

serotonin-transporter-linked polymorphic region

6-OHDA

6-hydroxydopamine

AA

arachidonic acid

AD

Alzheimer’s disease

BBB

blood brain barrier

Bcl-2

B-cell lymphoma-2

BDNF

brain-derived neurotrophic factor

cAMP

cyclic adenosine monophosphate

CNS

central nervous system

COX-2

cyclooxygenase-2

CREB

cAMP response element-binding protein

CRH

corticotrophin-releasing hormone

CSF

cerebrospinal fluid

DA

dopamine

DHA

docosahexaenoic acid

GDNF

glial cell line-derived neurotrophic factor

IDO

indoleamine 2,3-dioxygenase

ICE

interleukin-converting enzyme

i.c.v.

intracerebroventricular

IFN

interferon

IGF

insulin-like growth factor

IκB

inhibitor of kappaB

IL

interleukin

iNOS

inducible nitric oxide synthase

JAK

janus kinase

JNK

c-Jun N-terminal kinase

LRKK2

leucine rich repeat kinase 2

LPS

lipopolysaccharide

MAPK

mitogen-activated protein kinase

MCAO

middle cerebral artery occlusion

MHC

major histocompatibility complex

MnSOD

manganese superoxide dismutase

MPTP

1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine

mRNA

messenger ribonucleic acid

NADPH

nicotinamide adenine dinucleotide phosphate

NE

norepinephrine

NFκB

nuclear factor kappaB

NGF

nerve growth factor

NMDA

N-methyl D-aspartate

NO

nitric oxide

NSAID

nonsteroidal anti-inflammatory drug

PD

Parkinson’s disease

PG

prostaglandin

ROS

reactive oxygen species

SNc

substantia nigra pars compacta

STAT

signal transducer and activator of transcription

TGF

transforming growth factor

Th1

T helper type-1

TNF-α

tumor necrosis factor-alpha

References

  1. 1.
    Nuyen J, Schellevis FG, Satariano WA, et al. Comorbidity was associated with neurologic and psychiatric diseases: a general practice-based controlled study. J Clin Epidemiol 2006; 59(12):1274–1284PubMedCrossRefGoogle Scholar
  2. 2.
    Raskind MA. Diagnosis and treatment of depression comorbid with neurologic disorders. Am J Med 2008; 121(11 Suppl 2):28–37CrossRefGoogle Scholar
  3. 3.
    Strober LB, Arnett PA. Assessment of depression in three medically ill, elderly populations: Alzheimer’s disease, Parkinson’s disease, and stroke. Clin Neuropsychol 2009; 23(2):205–230PubMedCrossRefGoogle Scholar
  4. 4.
    Chen JK, Johnston KM, Petrides M, et al. Neural substrates of symptoms of depression following concussion in male athletes with persisting postconcussion symptoms. Arch Gen Psychiatry 2008; 65(1):81–89PubMedCrossRefGoogle Scholar
  5. 5.
    Forsaa EB, Larsen JP, Wentzel-Larsen T, et al. Predictors and course of health-related quality of life in Parkinson’s disease. Mov Disord 2008; 23(10):1420–1427PubMedCrossRefGoogle Scholar
  6. 6.
    Rahman S, Griffin HJ, Quinn NP, et al. Quality of life in Parkinson’s disease: the relative importance of the symptoms. Mov Disord 2008; 23(10):1428–1434PubMedCrossRefGoogle Scholar
  7. 7.
    Starkstein SE, Mizrahi R. Depression in Alzheimer’s disease. Expert Rev Neurother 2006; 6(6):887–895PubMedCrossRefGoogle Scholar
  8. 8.
    Tröster AI, Stalp LD, Paolo AM, et al. Neuropsychological impairment in Parkinson’s disease with and without depression. Arch Neurol 1995; 52(12):1164–1169PubMedCrossRefGoogle Scholar
  9. 9.
    Rapp MA, Schnaider-Beeri M, Grossman HT, et al. Increased hippocampal plaques and tangles in patients with Alzheimer disease with a lifetime history of major depression. Arch Gen Psychiatry 2006; 63(2):161–167PubMedCrossRefGoogle Scholar
  10. 10.
    Rapp MA, Schnaider-Beeri M, Purohit DP, Perl DP, Haroutunian V, Sano M. Increased neurofibrillary tangles in patients with Alzheimer disease with comorbid depression. Am J Geriatr Psychiatry 2008; 16(2):168–174PubMedCrossRefGoogle Scholar
  11. 11.
    Pålhagen SE, Carlsson M, Curman E, et al. Depressive illness in Parkinson’s disease–indication of a more advanced and widespread neurodegenerative process? Acta Neurol Scand 2008; 117(5):295–304PubMedCrossRefGoogle Scholar
  12. 12.
    Stella F, Banzato CE, Barasnevicius Quagliato EM, et al. Depression in patients with Parkinson’s disease: impact on functioning. J Neurol Sci 2008; 272(1–2):158–163PubMedCrossRefGoogle Scholar
  13. 13.
    Mast BT, MacNeill SE, Lichtenberg PA. Post-stroke and clinically-defined vascular depression in geriatric rehabilitation patients. Am J Geriatr Psychiatry 2004; 12(1):84–92PubMedGoogle Scholar
  14. 14.
    Han MK, Huh Y, Lee SB, et al. Prevalence of stroke and transient ischemic attack in Korean elders. Findings from the Korean longitudinal study on health and aging (KLoSHA). Stroke 2009; 40(3):966–969Google Scholar
  15. 15.
    Hayley S, Anisman H. Multiple mechanisms of cytokine action in neurodegenerative and psychiatric states: neurochemical and molecular substrates. Curr Pharm Des 2005; 11(8):947–962PubMedCrossRefGoogle Scholar
  16. 16.
    Anisman H, Merali Z, Poulter MO, et al. Cytokines as a precipitant of depressive illness: animal and human studies. Curr Pharm Des 2005; 11(8):963–972PubMedCrossRefGoogle Scholar
  17. 17.
    Hasler G, Drevets WC, Manji HK, et al. Discovering endophenotypes for major depression. Neuropsychopharmacology 2004; 29(10):1765–1781PubMedCrossRefGoogle Scholar
  18. 18.
    Benazzi F. Various forms of depression. Dialogues Clin Neurosci 2006; 8(2):151–161PubMedGoogle Scholar
  19. 19.
    Lemke MR, Fuchs G, Gemende I, et al. Depression and Parkinson’s disease. J Neurol 2004; 251(Suppl 6):24–27Google Scholar
  20. 20.
    Tharwani HM, Yerramsetty P, Mannelli P, et al. Recent advances in poststroke depression. Curr Psychiatry Rep 2007; 9(3):225–231PubMedCrossRefGoogle Scholar
  21. 21.
    Kauhanen M, Korpelainen JT, Hiltunen P, et al. Poststroke depression correlates with cognitive impairment and neurological deficits. Stroke 1999; 30(9):1875–1880PubMedCrossRefGoogle Scholar
  22. 22.
    Costa A, Peppe A, Carlesimo GA, et al. Major and minor depression in Parkinson’s disease: a neuropsychological investigation. Eur J Neurol 2006; 13(9):972–980PubMedCrossRefGoogle Scholar
  23. 23.
    Ehrt U, Brønnick K, Leentjens AF, et al. Depressive symptom profile in Parkinson’s disease: a comparison with depression in elderly patients without Parkinson’s disease. Int J Geriatr Psychiatry 2006; 21(3):252–258PubMedCrossRefGoogle Scholar
  24. 24.
    Hayley S, Merali Z, Anisman H. Stress and cytokine-elicited neuroendocrine and neurotransmitter sensitization: implications for depressive illness. Stress 2003; 6(1):19–32PubMedCrossRefGoogle Scholar
  25. 25.
    Anisman H, Merali Z, Hayley S. Sensitization associated with stressors and cytokine treatments. Brain Behav Immun 2003; 17(2):86–93PubMedCrossRefGoogle Scholar
  26. 26.
    Anisman H, Merali Z, Hayley S. Neurotransmitter, peptide and cytokine processes in relation to depressive disorder: comorbidity between depression and neurodegenerative disorders. Prog Neurobiol 2008; 85(1):1–74PubMedCrossRefGoogle Scholar
  27. 27.
    Anisman H. Cascading effects of stressors and inflammatory immune system activation: implications for major depressive disorder. J Psychiatry Neurosci 2009; 34(1):4–20PubMedGoogle Scholar
  28. 28.
    Jara LJ, Navarro C, Medina G, et al. Immune-neuroendocrine interactions and autoimmune diseases. Clin Dev Immunol 2006; 13(2–4):109–123PubMedCrossRefGoogle Scholar
  29. 29.
    Bhatt S, Zalcman S, Hassanain M, et al. Cytokine modulation of defensive rage behavior in the cat: role of GABAA and interleukin-2 receptors in the medial hypothalamus. Neuroscience 2005; 133(1):17–28PubMedCrossRefGoogle Scholar
  30. 30.
    Lynch DH, Campbell KA, Miller RE, et al. FasL/Fas and TNF/TNFR interactions in the regulation of immune responses and disease. Behring Inst Mitt 1996; (97):175–184Google Scholar
  31. 31.
    Kozak W, Conn CA, Klir JJ, et al. TNF soluble receptor and antiserum against TNF enhance lipopolysaccharide fever in mice. Am J Physiol 1995; 269(1 Pt 2):R23–R29PubMedGoogle Scholar
  32. 32.
    Avitsur R, Yirmiya R. The immunobiology of sexual behavior: gender differences in the suppression of sexual activity during illness. Pharmacol Biochem Behav 1999; 64(4):787–796PubMedCrossRefGoogle Scholar
  33. 33.
    Zalcman SS, Siegel A. The neurobiology of aggression and rage: role of cytokines. Brain Behav Immun 2006; 20(6):507–514PubMedCrossRefGoogle Scholar
  34. 34.
    Buchanan JB, Johnson RW. Regulation of food intake by inflammatory cytokines in the brain. Neuroendocrinology 2007; 86(3):183–190PubMedCrossRefGoogle Scholar
  35. 35.
    McGeer PL, McGeer EG. Glial reactions in Parkinson’s disease. Mov Disord 2008 15; 23(4):474–483Google Scholar
  36. 36.
    van Rossum D, Hanisch UK. Microglia. Metab Brain Dis 2004; 19(3–4):393–411PubMedCrossRefGoogle Scholar
  37. 37.
    Hanisch UK. Microglia as a source and target of cytokines. Glia 2002; 40(2):140–155PubMedCrossRefGoogle Scholar
  38. 38.
    Van Eldik LJ, Thompson WL, Ralay Ranaivo H, et al. Glia proinflammatory cytokine upregulation as a therapeutic target for neurodegenerative diseases: function-based and target-based discovery approaches. Int Rev Neurobiol 2007; 82:277–296PubMedCrossRefGoogle Scholar
  39. 39.
    Ho GJ, Drego R, Hakimian E, et al. Mechanisms of cell signaling and inflammation in Alzheimer’s disease. Curr Drug Targets Inflamm Allergy 2005; 4(2):247–256PubMedCrossRefGoogle Scholar
  40. 40.
    Ralay Ranaivo H, Craft JM, Hu W, et al. Glia as a therapeutic target: selective suppression of human amyloid-beta-induced upregulation of brain proinflammatory cytokine production attenuates neurodegeneration. J Neurosci 2006; 26(2):662–670PubMedCrossRefGoogle Scholar
  41. 41.
    del Zoppo GJ, Milner R, Mabuchi T, et al. Microglial activation and matrix protease generation during focal cerebral ischemia. Stroke 2007; 38(2 Suppl):646–651PubMedCrossRefGoogle Scholar
  42. 42.
    Shie FS, Woltjer RL. Manipulation of microglial activation as a therapeutic strategy in Alzheimer’s disease. Curr Med Chem 2007; 14(27):2865–2871PubMedCrossRefGoogle Scholar
  43. 43.
    Rajkowska G, Miguel-Hidalgo JJ. Gliogenesis and glial pathology in depression. CNS Neurol Disord Drug Targets 2007; 6(3):219–233PubMedCrossRefGoogle Scholar
  44. 44.
    McNally L, Bhagwagar Z, Hannestad J. Inflammation, glutamate, and glia in depression: a literature review. CNS Spectr 2008; 13(6):501–510PubMedGoogle Scholar
  45. 45.
    Maes M. Major depression and activation of the inflammatory response system. Adv Exp Med Biol 1999; 461:25–46PubMedCrossRefGoogle Scholar
  46. 46.
    Anisman H, Kokkinidis L, Merali Z. Further Evidence for the Depressive Effects of Cytokines: Anhedonia and Neurochemical Changes. Brain Behav Immun 2002; 16:544–556PubMedCrossRefGoogle Scholar
  47. 47.
    Schrag A, Hovris A, Morley D, et al. Young- versus older-onset Parkinson’s disease: impact of disease and psychosocial consequences. Mov Disord 2003; 18(11):1250–1256PubMedCrossRefGoogle Scholar
  48. 48.
    Anisman H, Matheson K. Stress, anhedonia and depression: Caveats Concerning Animal Models. Neurosci Biobehav Rev 2005; 29:525–546PubMedCrossRefGoogle Scholar
  49. 49.
    Sobel RM, Lotkowski S, Mandel S. Update on depression in neurologic illness: stroke, epilepsy, and multiple sclerosis. Curr Psychiatry Rep 2005; 7(5):396–403PubMedCrossRefGoogle Scholar
  50. 50.
    Mukherjee D, Levin RL, Heller W. The cognitive, emotional, and social sequelae of stroke: psychological and ethical concerns in post-stroke adaptation. Top Stroke Rehabil 2006; 13(4):26–35PubMedCrossRefGoogle Scholar
  51. 51.
    Rickards H. Depression in neurological disorders: an update. Curr Opin Psychiatry 2006; 19(3):294–298PubMedCrossRefGoogle Scholar
  52. 52.
    Frisina PG, Tenenbaum HR, Borod JC, et al. The effects of antidepressants in Parkinson’s disease: a meta-analysis. Int J Neurosci 2008; 118(5):667–682PubMedCrossRefGoogle Scholar
  53. 53.
    McEwen BS. Corticosteroids and hippocampal plasticity. Ann NY Acad Sci 1994; 746:134–142PubMedCrossRefGoogle Scholar
  54. 54.
    Sapolsky RM, Romero LM, Munck AU. How do glucocorticoids influence stress responses? Integrating permissive, suppressive, stimulatory, and preparative actions. Endocr Rev 2000; 21:55–89PubMedCrossRefGoogle Scholar
  55. 55.
    Kozorovitskiy Y, Gould E, Brustolim D, et al. Dominance hierarchy influences adult neurogenesis in the dentate gyrus. J. Neurosci 2004; 24:6755–6759PubMedCrossRefGoogle Scholar
  56. 56.
    Montaron MF, Drapeau E, Dupret D, et al. Lifelong corticosterone level determines age-related decline in neurogenesis and memory. Neurobiol Aging 2006; 27:645–654PubMedCrossRefGoogle Scholar
  57. 57.
    Zigmond MJ, Castro SL, Keefe KA, et al. Role of excitatory amino acids in the regulation of dopamine synthesis and release in the neostriatum. Amino Acids 1998; 14:57–62PubMedCrossRefGoogle Scholar
  58. 58.
    Kibel A, Drenjancević-Perić I. Impact of glucocorticoids and chronic stress on progression of Parkinson’s disease. Med Hypotheses 2008; 71(6):952–956PubMedCrossRefGoogle Scholar
  59. 59.
    Smith AD, Castro SL, Zigmond MJ. Stress-induced Parkinson’s disease: a working hypothesis. Physiol Behav 2002; 77(4–5):527–531PubMedCrossRefGoogle Scholar
  60. 60.
    Shiba M, Bower JH, Maraganore DM, et al. Anxiety disorders and depressive disorders preceding Parkinson’s disease: a case-control study. Mov Disord 2000; 15(4):669–677PubMedCrossRefGoogle Scholar
  61. 61.
    Nilsson FM, Kessing LV, Bolwig TG. Increased risk of developing Parkinson’s disease for patients with major affective disorder: a register study. Acta Psychiatr Scand 2001; 104(5):380–386PubMedCrossRefGoogle Scholar
  62. 62.
    Leentjens AF, Van den Akker M, Metsemakers JF, et al. Higher incidence of depression preceding the onset of Parkinson’s disease: a register study. Mov Disord 2003; 18(4):414–418PubMedCrossRefGoogle Scholar
  63. 63.
    Schuurman AG, van den Akker M, Ensinck KT, et al. Increased risk of Parkinson’s disease after depression: a retrospective cohort study. Neurology 2002; 58(10):1501–1504PubMedCrossRefGoogle Scholar
  64. 64.
    McDonald WM, Richard IH, DeLong MR. Prevalence, etiology, and treatment of depression in Parkinson’s disease. Biol Psychiatry 2003; 54:363–375PubMedCrossRefGoogle Scholar
  65. 65.
    Hawkins BT, Davis TP. The blood-brain barrier/neurovascular unit in health and disease. Pharmacol Rev 2005; 57(2):173–185PubMedCrossRefGoogle Scholar
  66. 66.
    Wyss-Coray T, Mucke L. Inflammation in neurodegenerative disease – a double-edged sword. Neuron 2002; 35(3):419–432PubMedCrossRefGoogle Scholar
  67. 67.
    Teismann P, Schulz JB. Cellular pathology of Parkinson’s disease: astrocytes, microglia and inflammation. Cell Tissue Res 2004; 318(1):149–161PubMedCrossRefGoogle Scholar
  68. 68.
    Tansey MG, McCoy MK, Frank-Cannon TC. Neuroinflammatory mechanisms in Parkinson’s disease: potential environmental triggers, pathways, and targets for early therapeutic intervention. Exp Neurol 2008; 208(1):1–25CrossRefGoogle Scholar
  69. 69.
    Rogers J, Mastroeni D, Leonard B, et al. Neuroinflammation in Alzheimer’s disease and Parkinson’s disease: are microglia pathogenic in either disorder? Int Rev Neurobiol 2007; 82:235–246PubMedCrossRefGoogle Scholar
  70. 70.
    Rothwell NJ, Hopkins SJ. Cytokines and the nervous system II: Actions and mechanisms of action. Trends in Neurosci 1995; 18:130–136CrossRefGoogle Scholar
  71. 71.
    Rothwell NJ. Cytokines – killers in the brain? J Physiol 1999; 514:3–17PubMedCrossRefGoogle Scholar
  72. 72.
    Elenkov IJ, Iezzoni DG, Daly A, et al. Cytokine dysregulation, inflammation and well-being. Neuroimmunomodulation 2005; 12:255–269PubMedCrossRefGoogle Scholar
  73. 73.
    Long NC, Morimoto A, Nakamori T, et al. Systemic injection of TNF- alpha attenuates fever due to IL-1 beta and LPS in rats. Am J Physiol 1992; 263:R987–R991PubMedGoogle Scholar
  74. 74.
    Goehler LE, Erisir A, Gaykema RP. Neural-immune interface in the rat area postrema. Neuroscience 2006; 140:1415–1434PubMedCrossRefGoogle Scholar
  75. 75.
    Banks WA, Ortz L, Plotkin SR, et al. Human interleukin (IL) 1 alpha, murine IL-1 alpha and murine IL-2 beta are transported from blood to brain in the mouse by a shared saturable mechanism. J Pharmacol Exper Ther 1991; 259:988–996Google Scholar
  76. 76.
    Banks WA. Physiology and pathology of the blood-brain barrier: implications for microbial pathogenesis, drug delivery and neurodegenerative disorders. J Neurovirol 1999; 5:538–555PubMedCrossRefGoogle Scholar
  77. 77.
    Gutierrez EG, Banks WA, Kastin AJ. Murine tumor necrosis factor alpha is transported from blood to brain in the mouse. J Neuroimmunol 1993; 47:169–176PubMedCrossRefGoogle Scholar
  78. 78.
    Maier SF, Watkins LR. Cytokines for psychologists: Implications of bidirectional immune-to-brain communication for understanding behavior, mood, and cognition. Psychol Rev 1998; 105:83–107PubMedCrossRefGoogle Scholar
  79. 79.
    Wieczorek M, Swiergiel AH, Pournajafi-Nazarloo H, et al. Physiological and behavioral responses to interleukin-1beta and LPS in vagotomized mice. Physiol Behav 2005; 85:500–511PubMedCrossRefGoogle Scholar
  80. 80.
    Esposito P, Gheorghe D, Kandere K, et al. Acute stress increases permeability of the blood-brain-barrier through activation of brain mast cells. Brain Res 2001; 888:117–127PubMedCrossRefGoogle Scholar
  81. 81.
    Theoharides TC, Konstantinidou AD. Corticotropin-releasing hormone and the blood-brain-barrier. Front Biosci 2007; 12:1615–1628PubMedCrossRefGoogle Scholar
  82. 82.
    Esposito P, Chandler N, Kandere K, et al. Corticotropin-releasing hormone and brain mast cells regulate blood-brain-barrier permeability induced by acute stress. J Pharmacol Exp Ther 2002; 303(3):1061–1066PubMedCrossRefGoogle Scholar
  83. 83.
    Wong D, Prameya R, Dorovini-Zis K. In vitro adhesion and migration of T lymphocytes across monolayers of human brain microvessel endothelial cells: regulation by ICAM-1, VCAM-1, E-selectin and PECAM-1. J Neuropathol Exp Neurol 1999; 58(2):138–152PubMedCrossRefGoogle Scholar
  84. 84.
    de Vries HE, Blom-Roosemalen MC, van Oosten M, et al. The influence of cytokines on the integrity of the blood-brain barrier in vitro. J Neuroimmunol 1996; 64:37–43PubMedCrossRefGoogle Scholar
  85. 85.
    Saija A, Princi P, Lanza M, et al. Systemic cytokine administration can affect blood-brain barrier permeability in the rat. Life Sciences 1996; 56:775–784CrossRefGoogle Scholar
  86. 86.
    Cayrol R, Wosik K, Berard JL, et al. Activated leukocyte cell adhesion molecule promotes leukocyte trafficking into the central nervous system. Nat Immunol 2008; 9(2):137–145PubMedCrossRefGoogle Scholar
  87. 87.
    De Groot CJ, Woodroofe MN. The role of chemokines and chemokine receptors in CNS inflammation. Prog Brain Res 2001; 132:533–544PubMedCrossRefGoogle Scholar
  88. 88.
    Ubogu EE, Cossoy MB, Ransohoff RM. The expression and function of chemokines involved in CNS inflammation. Trends Pharmacol Sci 2006; 27(1):48–55PubMedCrossRefGoogle Scholar
  89. 89.
    Stamatovic SM, Dimitrijevic OB, Keep RF, et al. Inflammation and brain edema: new insights into the role of chemokines and their receptors. Acta Neurochir Suppl 2006; 96:444–450PubMedCrossRefGoogle Scholar
  90. 90.
    Rivest S. How circulating cytokines trigger the neural circuits that control the hypothalamic-pituitary-adrenal axis. Psychoneuroendocrinology 2001; 26:761–788PubMedCrossRefGoogle Scholar
  91. 91.
    Cunningham ET, De Souza EB. Interleukin 1 receptors in the brain and endocrine tissues. Immunol Today 1993; 14:171–176PubMedCrossRefGoogle Scholar
  92. 92.
    Kinouchi K, Brown G, Pasternak G, et al. Identification and characterization of receptors for tumor necrosis factor-a in the brain. Biochem Biophys Res Comm 1991; 181:1532–1538PubMedCrossRefGoogle Scholar
  93. 93.
    Konsman JP, Dantzer R. How the immune and nervous systems interact during disease-associated anorexia. Nutrition 2001; 17:664–668PubMedCrossRefGoogle Scholar
  94. 94.
    Nadeau S, Rivest S. Effects of circulating tumor necrosis factor on the neuronal activity and expression of the genes encoding the tumor necrosis factor receptors (p55 and p75) in the rat brain: a view from the blood-brain barrier. Neuroscience 1999; 93:1449–1464PubMedCrossRefGoogle Scholar
  95. 95.
    Schöbitz B, Reul JM, Holsboer F. The role of the hypothalamic-pituitary-adrenocortical system during inflammatory conditions. Crit Rev Neurobiol 1994; 8(4):263–291PubMedGoogle Scholar
  96. 96.
    Tancredi V. Tumor necrosis factor alters synaptic transmission in rat hippocampal slices. Neurosci Lett 1992; 146:176–178PubMedCrossRefGoogle Scholar
  97. 97.
    Masana MI, Heyes MP, Mefford IN. Indomethacin prevents increased catecholamine turnover in rat brain following systemic endotoxin challenge. Prog Neuro-Psychopharmacol Biol Psychiat 1990; 14:609–621CrossRefGoogle Scholar
  98. 98.
    Buttini M, Boddeke H. Peripheral lipopolysaccharide stimulation induces interleukin-1b messenger RNA in rat brain microglial cells. Neuroscience 1995; 65:523–530PubMedCrossRefGoogle Scholar
  99. 99.
    Johnson AB, Bake S, Lewis, DK, et al. Temporal expression of IL-1beta protein and mRNA in the brain after systemic LPS injection is affected by age and estrogen. J Neuroimmunol 2006; 174:82–91PubMedCrossRefGoogle Scholar
  100. 100.
    Kamm K, Vanderkolk W, Lawrence C, et al. The effect of traumatic brain injury upon the concentration and expression of interleukin-1beta and interleukin-10 in the rat. J Trauma 2006; 60:152–157PubMedCrossRefGoogle Scholar
  101. 101.
    Zhu Y, Saito K, Murakami Y, et al. Early increase in mRNA levels of pro-inflammatory cytokines and their interactions in the mouse hippocampus after transient global ischemia. Neurosci Lett 2006; 393:122–126PubMedCrossRefGoogle Scholar
  102. 102.
    Ledeboer A, Binnekade R, Brevé JJ, et al. Site-specific modulation of LPS-induced fever and interleukin-1 beta expression in rats by interleukin-10. Am J Physiol Regul Integr Comp Physiol 2002; 282(6):R1762–R1772PubMedGoogle Scholar
  103. 103.
    Turrin NP, Gayle D, Ilyin SE, et al. Pro-inflammatory and anti-inflammatory cytokine mRNA induction in the periphery and brain following intraperitoneal administration of bacterial lipopolysaccharide. Brain Res Bull 2001; 54(4):443–453PubMedCrossRefGoogle Scholar
  104. 104.
    Maier SF, Nguyen KT, Deak T, et al. Stress, learned helplessness, and brain interleukin-1 beta. Adv Exp Med Biol 1999; 461:235–249PubMedCrossRefGoogle Scholar
  105. 105.
    Miyahara S, Komori T, Fujiwara R, et al. Effects of repeated stress on expression of interleukin-6 (IL-6) and IL-6 receptor mRNAs in rat hypothalamus and midbrain. Life Sci 2000; 66:PL93–PL98CrossRefGoogle Scholar
  106. 106.
    Nguyen KT, Deak T, Owens SM, et al. Exposure to acute stress induces brain interleukin-1β protein in the rat. J Neurosci 1998; 19:2799–2805Google Scholar
  107. 107.
    Banks WA. Cytokines, CVSs, and the blood-brain-barrier. In: Ader R, Felten DL, Cohen N (eds) Psychoneuroimmunology, vol. 2. Academic Press, New York; 2001:483–498Google Scholar
  108. 108.
    Clausen BH, Lambertsen KL, Babcock AA, et al. Interleukin-1beta and tumor necrosis factor-alpha are expressed by different subsets of microglia and macrophages after ischemic stroke in mice. J Neuroinflammation 2008; 5:46PubMedCrossRefGoogle Scholar
  109. 109.
    Shen YQ, Hebert G, Lin LY, et al. Interleukine-1beta and interleukine-6 levels in striatum and other brain structures after MPTP treatment: influence of behavioral lateralization. J Neuroimmunol 2005; 158(1–2):14–25PubMedCrossRefGoogle Scholar
  110. 110.
    Qin L, Wu X, Block ML, et al. Systemic LPS causes chronic neuroinflammation and progressive neurodegeneration. Glia 2007; 55(5):453–462PubMedCrossRefGoogle Scholar
  111. 111.
    Patrignani P, Tacconelli S, Sciulli MG, et al. New insights into COX-2 biology and inhibition. Brain Res Brain Res Rev 2005; 48(2):352–359PubMedCrossRefGoogle Scholar
  112. 112.
    Phillis JW, Horrocks LA, Farooqui AA. Cyclooxygenases, lipoxygenases, and epoxygenases in CNS: their role and involvement in neurological disorders. Brain Res Rev 2006; 52(2):201–243PubMedCrossRefGoogle Scholar
  113. 113.
    Bazan NG, Fletcher BS, Herschman HR, et al. Platelet-activating factor and retinoic acid synergistically activate the inducible prostaglandin synthase gene. Proc Natl Acad Sci USA 1994; 91(12):5252–5256PubMedCrossRefGoogle Scholar
  114. 114.
    Davies NM, Good RL, Roupe KA, et al. Cyclooxygenase-3: axiom, dogma, anomaly, enigma or splice error? – Not as easy as 1, 2, 3. J Pharm Pharm Sci 2004; 7(2):217–226PubMedGoogle Scholar
  115. 115.
    Chandrasekharan NV, Dai H, Roos KL, et al. COX-3, a cyclooxygenase-1 variant inhibited by acetaminophen and other analgesic/antipyretic drugs: cloning, structure, and expression. Proc Natl Acad Sci USA 2002; 99(21):13926–13931PubMedCrossRefGoogle Scholar
  116. 116.
    Bazan NG. Synaptic lipid signaling: significance of polyunsaturated fatty acids and platelet-activating factor. J Lipid Res 2003; 44(12):2221–2233PubMedCrossRefGoogle Scholar
  117. 117.
    Chen C, Bazan NG. Lipid signaling: sleep, synaptic plasticity, and neuroprotection. Prostaglandins Other Lipid Mediat 2005; 77(1–4):65–76PubMedCrossRefGoogle Scholar
  118. 118.
    Yang H, Chen C. Cyclooxygenase-2 in synaptic signaling. Curr Pharm Des 2008; 14(14):1443–1451PubMedCrossRefGoogle Scholar
  119. 119.
    Minghetti L. Cyclooxygenase-2 (COX-2) in inflammatory and degenerative brain diseases. J Neuropathol Exp Neurol 2004; 63(9):901–910PubMedGoogle Scholar
  120. 120.
    Akundi RS, Candelario-Jalil E, Hess S, et al. Signal transduction pathways regulating cyclooxygenase-2 in lipopolysaccharide-activated primary rat microglia. Glia 2005; 51(3):199–208PubMedCrossRefGoogle Scholar
  121. 121.
    Elmquist JK, Breder CD, Sherin JE, et al. Intravenous lipopolysaccharide induces cyclooxygenase 2-like immunoreactivity in rat brain perivascular microglia and meningeal macrophages. J Comp Neurol 1997; 381(2):119–129PubMedCrossRefGoogle Scholar
  122. 122.
    Buttini M, Limonta S, Boddeke HW. Peripheral administration of lipopolysaccharide induces activation of microglial cells in rat brain. Neurochem Int 1996; 29(1):25–35PubMedCrossRefGoogle Scholar
  123. 123.
    Hoozemans JJ, Rozemuller JM, van Haastert ES, et al. Cyclooxygenase-1 and -2 in the different stages of Alzheimer’s disease pathology. Curr Pharm Des 2008; 14(14):1419–1427PubMedCrossRefGoogle Scholar
  124. 124.
    Candelario-Jalil E, Fiebich BL. Cyclooxygenase inhibition in ischemic brain injury. Curr Pharm Des 2008; 14(14):1401–1418PubMedCrossRefGoogle Scholar
  125. 125.
    Müller N, Schwarz MJ. COX-2 inhibition in schizophrenia and major depression. Curr Pharm Des 2008; 14(14):1452–1465PubMedCrossRefGoogle Scholar
  126. 126.
    Fahn S. Description of Parkinson’s disease as a clinical syndrome. Ann NY Acad Sci 2003; 991:1–14PubMedCrossRefGoogle Scholar
  127. 127.
    Olanow CW. The pathogenesis of cell death in Parkinson’s disease–2007. Mov. Disord 2007; 22(s17):S335–S432PubMedCrossRefGoogle Scholar
  128. 128.
    Blandini F, Nappi G, Tassorelli C, et al. Functional changes of the basal ganglia circuitry in Parkinson’s disease. Prog Neurobiol 2000; 62(1):63–88PubMedCrossRefGoogle Scholar
  129. 129.
    Klockgether T. Parkinson’s disease: clinical aspects. Cell Tissue Res 2004; 318(1):115–120PubMedCrossRefGoogle Scholar
  130. 130.
    Micieli G, Tosi P, Marcheselli S, et al. Autonomic dysfunction in Parkinson’s disease. Neurol Sci 2003; 24(Suppl 1):S32–S34PubMedCrossRefGoogle Scholar
  131. 131.
    Tissingh G, Berendse HW, Bergmans P, et al. Loss of olfaction in de novo and treated Parkinson’s disease: possible implications for early diagnosis. Mov Disord 2001; 16(1):41–46PubMedCrossRefGoogle Scholar
  132. 132.
    Riedel O, Klotsche J, Spottke A, et al. Cognitive impairment in 873 patients with idiopathic Parkinson’s disease. Results from the German Study on Epidemiology of Parkinson’s Disease with Dementia (GEPAD). J Neurol 2008; 255(2):255–264PubMedCrossRefGoogle Scholar
  133. 133.
    Frasure-Smith N, Lespérance F. Recent evidence linking coronary heart disease and depression. Can J Psychiatry 2006; 51(12):730–737PubMedGoogle Scholar
  134. 134.
    Lustman PJ, Clouse RE. Depression in diabetic patients: the relationship between mood and glycemic control. J Diabetes Complications 2005; 19(2):113–122PubMedGoogle Scholar
  135. 135.
    Croisier E, Graeber MB. Glial degeneration and reactive gliosis in alpha-synucleinopathies: the emerging concept of primary gliodegeneration. Acta Neuropathol 2006; 112(5):517–530PubMedCrossRefGoogle Scholar
  136. 136.
    Mukaetova-Ladinska EB, Hurt J, Jakes R, et al. Alpha-synuclein inclusions in Alzheimer and Lewy body diseases. J Neuropathol Exp Neurol 2000; 59(5):408–417PubMedGoogle Scholar
  137. 137.
    Takahashi H, Wakabayashi K. The cellular pathology of Parkinson’s disease. Neuropathology 2001; 21(4):315–322PubMedCrossRefGoogle Scholar
  138. 138.
    Maries E, Dass B, Collier TJ, et al. The role of alpha-synuclein in Parkinson’s disease: insights from animal models. Nat Rev Neurosci 2003; 4(9):727–738PubMedCrossRefGoogle Scholar
  139. 139.
    Lee VM, Trojanowski JQ. Mechanisms of Parkinson’s disease linked to pathological alpha-synuclein: new targets for drug discovery. Neuron 2006; 52(1):33–38PubMedCrossRefGoogle Scholar
  140. 140.
    Cooper AA, Gitler AD, Cashikar A, et al. Alpha-synuclein blocks ER-Golgi traffic and Rab1 rescues neuron loss in Parkinson’s models. Science 2006; 313(5785):324–328PubMedCrossRefGoogle Scholar
  141. 141.
    Gitler AD, Bevis BJ, Shorter J, et al. The Parkinson’s disease protein alpha-synuclein disrupts cellular Rab homeostasis. Proc Natl Acad Sci USA 2008; 105(1):145–150PubMedCrossRefGoogle Scholar
  142. 142.
    Kelada SN, Checkoway H, Kardia SL, et al. 5’ and 3’ region variability in the dopamine transporter gene (SLC6A3), pesticide exposure and Parkinson’s disease risk: a hypothesis-generating study. Hum Mol Genet 2006; 15(20):3055–3062PubMedCrossRefGoogle Scholar
  143. 143.
    Singh M, Khan AJ, Shah PP, et al. Polymorphism in environment responsive genes and association with Parkinson disease. Mol Cell Biochem 2008; 312(1–2):131–138PubMedCrossRefGoogle Scholar
  144. 144.
    Wilk JB, Tobin JE, Suchowersky O, et al. Herbicide exposure modifies GSTP1 haplotype association to Parkinson onset age: the GenePD Study. Neurology 2006; 67(12):2206–2210PubMedCrossRefGoogle Scholar
  145. 145.
    Hancock DB, Martin ER, Mayhew GM, et al. Pesticide exposure and risk of Parkinson’s disease: a family-based case-control study. BMC Neurol 2008; 8:6PubMedCrossRefGoogle Scholar
  146. 146.
    Stepens A, Logina I, Liguts V, et al. A Parkinsonian syndrome in methcathinone users and the role of manganese. N Engl J Med 2008; 358(10):1009–1017PubMedCrossRefGoogle Scholar
  147. 147.
    Betarbet R, Sherer TB, MacKenzie G, et al. Chronic systemic pesticide exposure reproduces features of Parkinson’s disease. Nat Neurosci 2000; 3(12):1301–1306PubMedCrossRefGoogle Scholar
  148. 148.
    Giasson BI, Lee VM. A new link between pesticides and Parkinson’s disease. Nat Neurosci 2000; 3(12):1227–1228PubMedCrossRefGoogle Scholar
  149. 149.
    Landrigan PJ, Sonawane B, Butler RN, et al. Early environmental origins of neurodegenerative disease in later life. Environ Health Perspect 2005; 113(9):1230–1233PubMedCrossRefGoogle Scholar
  150. 150.
    Hatcher JM, Pennell KD, Miller GW. Parkinson’s disease and pesticides: a toxicological perspective. Trends Pharmacol Sci 2008; 29(6):322–329PubMedCrossRefGoogle Scholar
  151. 151.
    Dick FD, De Palma G, Ahmadi A, et al. Environmental risk factors for Parkinson’s disease and parkinsonism: the Geoparkinson study. Occup Environ Med 2007; 64(10):666–672PubMedCrossRefGoogle Scholar
  152. 152.
    Priyadarshi A, Khuder SA, Schaub EA, et al. Environmental risk factors and Parkinson’s disease: a metaanalysis. Environ Res 2001; 86(2):122–127PubMedCrossRefGoogle Scholar
  153. 153.
    Firestone JA, Smith-Weller T, Franklin G, et al. Pesticides and risk of Parkinson disease: a population-based case-control study. Arch Neurol 2005; 62(1):91–95PubMedCrossRefGoogle Scholar
  154. 154.
    Fong CS, Wu RM, Shieh JC, et al. Pesticide exposure on southwestern Taiwanese with MnSOD and NQO1 polymorphisms is associated with increased risk of Parkinson’s disease. Clin Chim Acta 2007; 378(1–2):136–141PubMedCrossRefGoogle Scholar
  155. 155.
    Dhillon AS, Tarbutton GL, Levin JL, et al. Pesticide/environmental exposures and Parkinson’s disease in East Texas. J Agromedicine 2008; 13(1):37–48PubMedCrossRefGoogle Scholar
  156. 156.
    Costello S, Cockburn M, Bronstein J, et al. Parkinson’s disease and residential exposure to maneb and paraquat from agricultural applications in the central valley of California. Am J Epidemiol 2009; 169(8):919–926PubMedCrossRefGoogle Scholar
  157. 157.
    Tsui JK, Calne DB, Wang Y, et al. Occupational risk factors in Parkinson’s disease. Can J Public Health 1991; 90:334–337Google Scholar
  158. 158.
    Semchuk KM, Love EJ, Lee RG. Parkinson’s disease and exposure to agricultural work and pesticide chemicals. Neurology 1992; 42(7):1328–1335PubMedCrossRefGoogle Scholar
  159. 159.
    Petrovitch H, Ross GW, Abbott RD, et al. Plantation work and risk of Parkinson disease in a population-based longitudinal study. Arch Neurol 2002; 59(11):1787–1792PubMedCrossRefGoogle Scholar
  160. 160.
    Baldi I, Cantagrel A, Lebailly P, et al. Association between Parkinson’s disease and exposure to pesticides in southwestern France. Neuroepidemiology 2003; 22(5):305–310PubMedCrossRefGoogle Scholar
  161. 161.
    Liou HH, Tsai MC, Chen CJ, et al. Environmental risk factors and Parkinson’s disease: a case-control study in Taiwan. Neurology 1997; 48(6):1583–1588PubMedCrossRefGoogle Scholar
  162. 162.
    McCormack AL, Thiruchelvam M, Manning-Bog AB, et al. Environmental risk factors and Parkinson’s disease: selective degeneration of nigral dopaminergic neurons caused by the herbicide paraquat. Neurobiol Dis 2002; 10(2):119–127PubMedCrossRefGoogle Scholar
  163. 163.
    McCormack AL, Di Monte DA. Effects of L-dopa and other amino acids against paraquat-induced nigrostriatal degeneration. J Neurochem 2003; 85(1):82–86PubMedCrossRefGoogle Scholar
  164. 164.
    McCormack AL, Atienza JG, Johnston LC, et al. Role of oxidative stress in paraquat-induced dopaminergic cell degeneration. J Neurochem 2005; 93(4):1030–1037PubMedCrossRefGoogle Scholar
  165. 165.
    Purisai MG, McCormack AL, Cumine S, et al. Microglial activation as a priming event leading to paraquat-induced dopaminergic cell degeneration. Neurobiol Dis 2007; 25(2):392–400PubMedCrossRefGoogle Scholar
  166. 166.
    Fei Q, McCormack AL, Di Monte DA, et al. Paraquat neurotoxicity is mediated by a Bak-dependent mechanism. J Biol Chem 2008; 283(6):3357–3364PubMedCrossRefGoogle Scholar
  167. 167.
    Betarbet R, Canet-Aviles RM, Sherer TB, et al. Intersecting pathways to neurodegeneration in Parkinson’s disease: effects of the pesticide rotenone on DJ-1, alpha-synuclein, and the ubiquitin-proteasome system. Neurobiol Dis 2006; 22(2):404–420PubMedCrossRefGoogle Scholar
  168. 168.
    Ossowska K, Smiałowska M, Kuter K, et al. Degeneration of dopaminergic mesocortical neurons and activation of compensatory processes induced by a long-term paraquat administration in rats: implications for Parkinson’s disease. Neuroscience 2006; 141(4):2155–2165PubMedCrossRefGoogle Scholar
  169. 169.
    Brooks AI, Chadwick CA, Gelbard HA, et al. Paraquat elicited neurobehavioral syndrome caused by dopaminergic neuron loss. Brain Res 1999; 823(1–2):1–10PubMedCrossRefGoogle Scholar
  170. 170.
    Li X, Yin J, Cheng CM, et al. Paraquat induces selective dopaminergic nigrostriatal degeneration in aging C57BL/6 mice. Chin Med J (Engl) 2005; 118(16):1357–1361Google Scholar
  171. 171.
    Litteljohn D, Mangano EN, Hayley S. Cyclooxygenase-2 deficiency modifies the neurochemical effects, motor impairment and co-morbid anxiety provoked by paraquat administration in mice. Eur J Neurosci 2008; 28(4):707–716PubMedCrossRefGoogle Scholar
  172. 172.
    Uversky VN, Li J, Fink AL. Pesticides directly accelerate the rate of alpha-synuclein fibril formation: a possible factor in Parkinson’s disease. FEBS Lett 2001; 500(3):105–108PubMedCrossRefGoogle Scholar
  173. 173.
    Manning-Bog AB, McCormack AL, Li J, et al. The herbicide paraquat causes up-regulation and aggregation of alpha-synuclein in mice: paraquat and alpha-synuclein. J Biol Chem 2002; 277(3):1641–1644PubMedCrossRefGoogle Scholar
  174. 174.
    Yang W, Tiffany-Castiglioni E. The bipyridyl herbicide paraquat induces proteasome dysfunction in human neuroblastoma SH-SY5Y cells. J Toxicol Environ Health A 2007; 70(21):1849–1857PubMedCrossRefGoogle Scholar
  175. 175.
    Fernagut PO, Hutson CB, Fleming SM, et al. Behavioral and histopathological consequences of paraquat intoxication in mice: effects of alpha-synuclein over-expression. Synapse 2007; 61(12):991–1001PubMedCrossRefGoogle Scholar
  176. 176.
    Uversky VN, Li J, Bower K, et al. Synergistic effects of pesticides and metals on the fibrillation of alpha-synuclein: implications for Parkinson’s disease. Neurotoxicology 2002; 23(4–5):527–536PubMedCrossRefGoogle Scholar
  177. 177.
    Peng J, Peng L, Stevenson FF, et al. Iron and paraquat as synergistic environmental risk factors in sporadic Parkinson’s disease accelerate age-related neurodegeneration. J Neurosci 2007; 27(26):6914–6922PubMedCrossRefGoogle Scholar
  178. 178.
    Thiruchelvam M, Brockel BJ, Richfield EK, et al. Potentiated and preferential effects of combined paraquat and maneb on nigrostriatal dopamine systems: environmental risk factors for Parkinson’s disease? Brain Res 2000; 873(2):225–234PubMedCrossRefGoogle Scholar
  179. 179.
    Thiruchelvam M, Richfield EK, Baggs RB, et al. The nigrostriatal dopaminergic system as a preferential target of repeated exposures to combined paraquat and maneb: implications for Parkinson’s disease. J Neurosci 2000; 20(24):9207–9214PubMedGoogle Scholar
  180. 180.
    Erroi A, Bianchi M, Ghezzi P. The pneumotoxicant paraquat potentiates IL-1 and TNF production by human mononuclear cells. Agents Actions 1992; 36(1–2):66–69PubMedCrossRefGoogle Scholar
  181. 181.
    Peng J, Mao XO, Stevenson FF, et al. The herbicide paraquat induces dopaminergic nigral apoptosis through sustained activation of the JNK pathway. J Biol Chem 2004; 279(31):32626–32632PubMedCrossRefGoogle Scholar
  182. 182.
    Hatcher JM, Richardson JR, Guillot TS, et al. Dieldrin exposure induces oxidative damage in the mouse nigrostriatal dopamine system. Exp Neurol 2007; 204(2):619–630PubMedCrossRefGoogle Scholar
  183. 183.
    Miller RL, James-Kracke M, Sun GY, et al. Oxidative and inflammatory pathways in Parkinson’s disease. Neurochem Res 2009; 34(1):55–65PubMedCrossRefGoogle Scholar
  184. 184.
    Gao HM, Liu B, Hong JS. Critical role for microglial NADPH oxidase in rotenone-induced degeneration of dopaminergic neurons. J Neurosci 2003; 23(15):6181–6187PubMedGoogle Scholar
  185. 185.
    Sherer TB, Betarbet R, Testa CM, et al. Mechanism of toxicity in rotenone models of Parkinson’s disease. J Neurosci 2003; 23(34):10756–10764PubMedGoogle Scholar
  186. 186.
    Testa CM, Sherer TB, Greenamyre JT. Rotenone induces oxidative stress and dopaminergic neuron damage in organotypic substantia nigra cultures. Brain Res Mol Brain Res 2005; 134(1):109–118PubMedCrossRefGoogle Scholar
  187. 187.
    Miller RL, Sun GY, Sun AY. Cytotoxicity of paraquat in microglial cells: Involvement of PKCdelta- and ERK1/2-dependent NADPH oxidase. Brain Res 2007; 1167:129–139PubMedCrossRefGoogle Scholar
  188. 188.
    Mangano EN, Hayley S. Inflammatory priming of the substantia nigra influences the impact of later paraquat exposure: Neuroimmune sensitization of neurodegeneration. Neurobiol Aging 2008; 30(9):1361–1378Google Scholar
  189. 189.
    Teismann P, Vila M, Choi DK, et al. COX-2 and neurodegeneration in Parkinson’s disease. Ann N Y Acad Sci 2003; 991:272–277PubMedCrossRefGoogle Scholar
  190. 190.
    Hunot S, Vila M, Teismann P, et al. JNK-mediated induction of cyclooxygenase 2 is required for neurodegeneration in a mouse model of Parkinson’s disease. Proc Natl Acad Sci USA 2004; 101(2):665–670PubMedCrossRefGoogle Scholar
  191. 191.
    Stefanova E, Potrebic A, Ziropadja L, et al. Depression predicts the pattern of cognitive impairment in early Parkinson’s disease. Neurol Sci 2006; 248(1–2):131–137Google Scholar
  192. 192.
    Visser M, van Rooden SM, Verbaan D, et al. A comprehensive model of health-related quality of life in Parkinson’s disease. J Neurol 2008; 255(10):1580–1587PubMedCrossRefGoogle Scholar
  193. 193.
    Rinne JO, Portin R, Ruottinen H, et al. Cognitive impairment and the brain dopaminergic system in Parkinson disease: [18F]fluorodopa positron emission tomographic study. Arch Neurol 2000; 57(4):470–475PubMedCrossRefGoogle Scholar
  194. 194.
    Brück A, Portin R, Lindell A, et al. Positron emission tomography shows that impaired frontal lobe functioning in Parkinson’s disease is related to dopaminergic hypofunction in the caudate nucleus. Neurosci Lett 2001; 311(2):81–84PubMedCrossRefGoogle Scholar
  195. 195.
    Jokinen P, Brück A, Aalto S, et al. Impaired cognitive performance in Parkinson’s disease is related to caudate dopaminergic hypofunction and hippocampal atrophy. Parkinsonism Relat Disord 2009; 15(2):88–93PubMedCrossRefGoogle Scholar
  196. 196.
    Cardoso EF, Maia FM, Fregni F, et al. Depression in Parkinson’s disease: convergence from voxel-based morphometry and functional magnetic resonance imaging in the limbic thalamus. Neuroimage 2009; 47(2):467–472PubMedCrossRefGoogle Scholar
  197. 197.
    Lin TP, Carbon M, Tang C, et al. Metabolic correlates of subthalamic nucleus activity in Parkinson’s disease. Brain 2008; 131(Pt 5):1373–1380PubMedGoogle Scholar
  198. 198.
    Temel Y, Boothman LJ, Blokland A, et al. Inhibition of 5-HT neuron activity and induction of depressive-like behavior by high-frequency stimulation of the subthalamic nucleus. Proc Natl Acad Sci USA 2007; 104(43):17087–17092PubMedCrossRefGoogle Scholar
  199. 199.
    Berg D. Biomarkers for the early detection of Parkinson’s and Alzheimer’s disease. Neurodegener Dis 2008; 5(3–4):133–136PubMedCrossRefGoogle Scholar
  200. 200.
    Taylor AE, Saint-Cyr JA, Lang AE. Frontal lobe dysfunction in Parkinson’s disease. The cortical focus of neostriatal outflow. Brain 1986; 109(Pt 5):845–883PubMedCrossRefGoogle Scholar
  201. 201.
    Chan-Palay V, Asan E. Alterations in catecholamine neurons of the locus coeruleus in senile dementia of the Alzheimer type and in Parkinson’s disease with and without dementia and depression. J Comp Neurol 1989; 287(3):373–392PubMedCrossRefGoogle Scholar
  202. 202.
    Becker T, Becker G, Seufert J, et al. Parkinson’s disease and depression: evidence for an alteration of the basal limbic system detected by transcranial sonography. J Neurol Neurosurg Psychiatry 1997; 63(5):590–596PubMedCrossRefGoogle Scholar
  203. 203.
    Sasaki M, Shibata E, Tohyama K, et al. Neuromelanin magnetic resonance imaging of locus ceruleus and substantia nigra in Parkinson’s disease. Neuroreport 2006; 17(11):1215–1218PubMedCrossRefGoogle Scholar
  204. 204.
    Braak H, Sastre M, Del Tredici K. Development of alpha-synuclein immunoreactive astrocytes in the forebrain parallels stages of intraneuronal pathology in sporadic Parkinson’s disease. Acta Neuropathol 2007; 114(3):231–241PubMedCrossRefGoogle Scholar
  205. 205.
    Gesi M, Soldani P, Giorgi FS, et al. The role of the locus coeruleus in the development of Parkinson’s disease. Neurosci Biobehav Rev 2000; 24(6):655–668PubMedCrossRefGoogle Scholar
  206. 206.
    Zarow C, Lyness SA, Mortimer JA, et al. Neuronal loss is greater in the locus coeruleus than nucleus basalis and substantia nigra in Alzheimer and Parkinson diseases. Arch Neurol 2003; 60(3):337–341PubMedCrossRefGoogle Scholar
  207. 207.
    Del Tredici K, Rüb U, De Vos RA, et al. Where does parkinson disease pathology begin in the brain? J Neuropathol Exp Neurol 2002; 61(5):413–426PubMedGoogle Scholar
  208. 208.
    Calò M, Iannöne M, Passafaro M, et al. Selective vulnerability of hippocampal CA3 neurones after microinfusion of paraquat into the rat substantia nigra or into the ventral tegmental area. J Comp Pathol 1990; 103(1):73–78PubMedCrossRefGoogle Scholar
  209. 209.
    Bagetta G, Corasaniti MT, Iannone M, et al. Production of limbic motor seizures and brain damage by systemic and intracerebral injections of paraquat in rats. Pharmacol Toxicol 1992; 71(6):443–448PubMedCrossRefGoogle Scholar
  210. 210.
    Ossowska K, Wardas J, Smiałowska M, et al. A slowly developing dysfunction of dopaminergic nigrostriatal neurons induced by long-term paraquat administration in rats: an animal model of preclinical stages of Parkinson’s disease? Eur J Neurosci 2005; 22(6):1294–1304PubMedCrossRefGoogle Scholar
  211. 211.
    Kuter K, Smiałowska M, Wierońska J, et al. Toxic influence of subchronic paraquat administration on dopaminergic neurons in rats. Brain Res 2007; 1155:196–207PubMedCrossRefGoogle Scholar
  212. 212.
    Chanyachukul T, Yoovathaworn K, Thongsaard W, et al. Attenuation of paraquat-induced motor behavior and neurochemical disturbances by L-valine in vivo. Toxicol Lett 2004; 150(3):259–269PubMedCrossRefGoogle Scholar
  213. 213.
    Höglinger GU, Féger J, Prigent A, et al. Chronic systemic complex I inhibition induces a hypokinetic multisystem degeneration in rats. J Neurochem 2003; 84(3):491–502PubMedCrossRefGoogle Scholar
  214. 214.
    Corasaniti MT, Bagetta G, Rodinò P, et al. Neurotoxic effects induced by intracerebral and systemic injection of paraquat in rats. Hum Exp Toxicol 1992; 11(6):535–539PubMedCrossRefGoogle Scholar
  215. 215.
    Hu SC, Chang FW, Sung YJ, et al. Neurotoxic effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine in the substantia nigra and the locus coeruleus in BALB/c mice. J Pharmacol Exp Ther 1991; 259(3):1379–1387PubMedGoogle Scholar
  216. 216.
    Mavridis M, Degryse AD, Lategan AJ, et al. Effects of locus coeruleus lesions on parkinsonian signs, striatal dopamine and substantia nigra cell loss after 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine in monkeys: a possible role for the locus coeruleus in the progression of Parkinson’s disease. Neuroscience 1991; 41(2–3):507–523PubMedCrossRefGoogle Scholar
  217. 217.
    Marien M, Briley M, Colpaert F. Noradrenaline depletion exacerbates MPTP-induced striatal dopamine loss in mice. Eur J Pharmacol 1993; 236(3):487–489PubMedCrossRefGoogle Scholar
  218. 218.
    Bing G, Zhang Y, Watanabe Y, et al. Locus coeruleus lesions potentiate neurotoxic effects of MPTP in dopaminergic neurons of the substantia nigra. Brain Res 1994; 668(1–2):261–265PubMedCrossRefGoogle Scholar
  219. 219.
    Fornai F, Alessandrì MG, Torracca MT, et al. Effects of noradrenergic lesions on MPTP/MPP+ kinetics and MPTP-induced nigrostriatal dopamine depletions. J Pharmacol Exp Ther 1997; 283(1):100–107PubMedGoogle Scholar
  220. 220.
    Reches A, Meiner Z. The locus coeruleus and dopaminergic function in rat brain: implications to parkinsonism. Brain Res Bull 1992; 28(5):663–666PubMedCrossRefGoogle Scholar
  221. 221.
    Mann DM, Yates PO. Pathological basis for neurotransmitter changes in Parkinson’s disease. Neuropathol Appl Neurobiol 1983; 9(1):3–19PubMedCrossRefGoogle Scholar
  222. 222.
    de Lima MN, Laranja DC, Caldana F, et al. Selegiline protects against recognition memory impairment induced by neonatal iron treatment. Exp Neurol 2005; 196(1):177–183PubMedCrossRefGoogle Scholar
  223. 223.
    Kooncumchoo P, Sharma S, Porter J, et al. Coenzyme Q(10) provides neuroprotection in iron-induced apoptosis in dopaminergic neurons. J Mol Neurosci 2006; 28(2):125–141PubMedCrossRefGoogle Scholar
  224. 224.
    Kaur D, Peng J, Chinta SJ, et al. Increased murine neonatal iron intake results in Parkinson-like neurodegeneration with age. Neurobiol Aging 2007; 28(6):907–913PubMedCrossRefGoogle Scholar
  225. 225.
    Perl DP, Olanow CW. The neuropathology of manganese-induced Parkinsonism. J Neuropathol Exp Neurol 2007; 66(8):675–682PubMedCrossRefGoogle Scholar
  226. 226.
    Cooper JF, Kusnecov AW. Methylmercuric chloride induces activation of neuronal stress circuitry and alters exploratory behavior in the mouse. Neuroscience 2007; 148(4):1048–1064PubMedCrossRefGoogle Scholar
  227. 227.
    Bowler RM, Gysens S, Diamond E, et al. Neuropsychological sequelae of exposure to welding fumes in a group of occupationally exposed men. Int J Hyg Environ Health 2003; 206(6):517–529PubMedCrossRefGoogle Scholar
  228. 228.
    Bowler RM, Gysens S, Diamond E, et al. Manganese exposure: neuropsychological and neurological symptoms and effects in welders. Neurotoxicology 2006; 27(3):315–326PubMedCrossRefGoogle Scholar
  229. 229.
    Bowler RM, Roels HA, Nakagawa S, et al. Dose-effect relationships between manganese exposure and neurological, neuropsychological and pulmonary function in confined space bridge welders. Occup Environ Med 2007; 64(3):167–177PubMedCrossRefGoogle Scholar
  230. 230.
    Fischer C, Fredriksson A, Eriksson P. Neonatal co-exposure to low doses of an ortho-PCB (PCB 153) and methyl mercury exacerbate defective developmental neurobehavior in mice. Toxicology 2007 [Epub ahead of print]Google Scholar
  231. 231.
    Cory-Slechta DA, Thiruchelvam M, Barlow BK, et al. Developmental pesticide models of the Parkinson disease phenotype. Environ Health Perspect 2005; 113(9):1263–1270PubMedCrossRefGoogle Scholar
  232. 232.
    Aldridge JE, Levin ED, Seidler FJ, et al. Developmental exposure of rats to chlorpyrifos leads to behavioral alterations in adulthood, involving serotonergic mechanisms and resembling animal models of depression. Environ Health Perspect 2005; 113(5):527–531PubMedCrossRefGoogle Scholar
  233. 233.
    Bertossi M, Girolamo F, Errede M, et al. Effects of methylmercury on the microvasculature of the developing brain. Neurotoxicology 2004; 25(5):849–857PubMedCrossRefGoogle Scholar
  234. 234.
    Fitsanakis VA, Piccola G, Aschner JL, et al. Characteristics of manganese (Mn) transport in rat brain endothelial (RBE4) cells, an in vitro model of the blood-brain barrier. Neurotoxicology 2006; 27(1):60–70PubMedCrossRefGoogle Scholar
  235. 235.
    Shi LZ, Zheng W. Early lead exposure increases the leakage of the blood-cerebrospinal fluid barrier, in vitro. Hum Exp Toxicol 2007; 26(3):159–167PubMedCrossRefGoogle Scholar
  236. 236.
    Dohgu S, Banks WA. Lipopolysaccharide-enhanced transcellular transport of HIV-1 across the blood-brain barrier is mediated by the p38 mitogen-activated protein kinase pathway. Exp Neurol 2008; 210(2):740–749PubMedCrossRefGoogle Scholar
  237. 237.
    Ravenstijn PG, Merlini M, Hameetman M, et al. The exploration of rotenone as a toxin for inducing Parkinson’s disease in rats, for application in BBB transport and PK-PD experiments. J Pharmacol Toxicol Methods 2008; 57(2):114–130PubMedCrossRefGoogle Scholar
  238. 238.
    Banks WA. The blood-brain barrier in psychoneuroimmunology. Neurol Clin 2006; 24(3):413–419PubMedCrossRefGoogle Scholar
  239. 239.
    Desai BS, Monahan AJ, Carvey PM, et al. Blood-brain barrier pathology in Alzheimer’s and Parkinson’s disease: implications for drug therapy. Cell Transplant 2007; 16(3):285–299PubMedGoogle Scholar
  240. 240.
    Peng CH, Chiou SH, Chen SJ, et al. Neuroprotection by Imipramine against lipopolysaccharide-induced apoptosis in hippocampus-derived neural stem cells mediated by activation of BDNF and the MAPK pathway. Eur Neuropsychopharmacol 2008; 18(2):128–140PubMedCrossRefGoogle Scholar
  241. 241.
    Lucassen PJ, Fuchs E, Czéh B. Antidepressant treatment with tianeptine reduces apoptosis in the hippocampal dentate gyrus and temporal cortex. Biol Psychiatry 2004; 55(8):789–796PubMedCrossRefGoogle Scholar
  242. 242.
    Müller N, Schwarz MJ, Dehning S, et al. The cyclooxygenase-2 inhibitor celecoxib has therapeutic effects in major depression: results of a double-blind, randomized, placebo controlled, add-on pilot study to reboxetine. Mol Psychiatry 2006; 11(7):680–684PubMedCrossRefGoogle Scholar
  243. 243.
    Peng Q, Masuda N, Jiang M, et al. The antidepressant sertraline improves the phenotype, promotes neurogenesis and increases BDNF levels in the R6/2 Huntington’s disease mouse model. Exp Neurol 2008; 210(1):154–163PubMedCrossRefGoogle Scholar
  244. 244.
    Taler M, Bar M, Korob I, et al. Evidence for an inhibitory immunomodulatory effect of selected antidepressants on rat splenocytes: possible relevance to depression and hyperactive-immune disorders. Int Immunopharmacol 2008; 8(4):526–533PubMedCrossRefGoogle Scholar
  245. 245.
    Pae CU, Marks DM, Han C, et al. Does minocycline have antidepressant effect? Biomed Pharmacother 2008; 62(5):308–311PubMedCrossRefGoogle Scholar
  246. 246.
    Faherty CJ, Raviie Shepherd K, Herasimtschuk A, et al. Environmental enrichment in adulthood eliminates neuronal death in experimental Parkinsonism. Brain Res Mol Brain Res 2005; 134(1):170–179PubMedCrossRefGoogle Scholar
  247. 247.
    Castrén E. Neurotrophic effects of antidepressant drugs. Curr Opin Pharmacol 2004; 4(1):58–64PubMedCrossRefGoogle Scholar
  248. 248.
    McEwen BS, Olié JP. Neurobiology of mood, anxiety, and emotions as revealed by studies of a unique antidepressant: tianeptine. Mol Psychiatry 2005; 10(6):525–537PubMedCrossRefGoogle Scholar
  249. 249.
    Huang YY, Peng CH, Yang YP, et al. Desipramine activated Bcl-2 expression and inhibited lipopolysaccharide-induced apoptosis in hippocampus-derived adult neural stem cells. J Pharmacol Sci 2007; 104(1):61–72PubMedCrossRefGoogle Scholar
  250. 250.
    Myint AM, Kim YK, Verkerk R, et al. Kynurenine pathway in major depression: evidence of impaired neuroprotection. J Affect Disord 2007; 98(1–2):143–151PubMedCrossRefGoogle Scholar
  251. 251.
    McKernan DP, Dinan TG, Cryan JF. “Killing the Blues”: A role for cellular suicide (apoptosis) in depression and the antidepressant response? Prog Neurobiol 2009; 88(4): 246–263Google Scholar
  252. 252.
    Castrén E. Neurotrophins as mediators of drug effects on mood, addiction, and neuroprotection. Mol Neurobiol 2004; 29(3):289–302PubMedCrossRefGoogle Scholar
  253. 253.
    Du Y, Ma Z, Lin S, et al. Minocycline prevents nigrostriatal dopaminergic neurodegeneration in the MPTP model of Parkinson’s disease. Proc Natl Acad Sci USA 2001; 98(25):14669–144674PubMedCrossRefGoogle Scholar
  254. 254.
    O’Connor JC, Lawson MA, André C, et al. Lipopolysaccharide-induced depressive-like behavior is mediated by indoleamine 2,3-dioxygenase activation in mice. Mol Psychiatry 2009; 14(5):511–522PubMedCrossRefGoogle Scholar
  255. 255.
    Molina-Hernández M, Téllez-Alcántara NP, Pérez-García J, et al. Desipramine or glutamate antagonists synergized the antidepressant-like actions of intra-nucleus accumbens infusions of minocycline in male Wistar rats. Prog Neuropsychopharmacol Biol Psychiatry 2008; 32(7):1660–1666PubMedCrossRefGoogle Scholar
  256. 256.
    Gao HM, Jiang J, Wilson B, et al. Microglial activation-mediated delayed and progressive degeneration of rat nigral dopaminergic neurons: relevance to Parkinson’s disease. J Neurochem 2002; 81(6):1285–1297PubMedCrossRefGoogle Scholar
  257. 257.
    Kim WG, Mohney RP, Wilson B, et al. Regional difference in susceptibility to lipopolysaccharide-induced neurotoxicity in the rat brain: role of microglia. J Neurosci 2000; 20:6309–6316PubMedGoogle Scholar
  258. 258.
    Höftberger R, Garzuly F, Dienes HP, et al. Fulminant central nervous system demyelination associated with interferon-alpha therapy and hepatitis C virus infection. Mult Scler 2007; 13(9):1100–1106PubMedCrossRefGoogle Scholar
  259. 259.
    Capuron L, Gumnick JF, Musselman DL, et al. Neurobehavioral effects of interferon-alpha in cancer patients: phenomenology and paroxetine responsiveness of symptom dimensions. Neuropsychopharmacology 2002; 26(5):643–652PubMedCrossRefGoogle Scholar
  260. 260.
    Raison CL, Demetrashvili M, Capuron L, et al. Neuropsychiatric adverse effects of interferon-alpha: recognition and management. CNS Drugs 2005; 19(2):105–123PubMedCrossRefGoogle Scholar
  261. 261.
    Hayley S, Brebner K, Lacosta S, et al. Sensitization to the effects of tumor necrosis factor-alpha: neuroendocrine, central monoamine, and behavioral variations. J Neurosci 1999; 19(13):5654–5665PubMedGoogle Scholar
  262. 262.
    Anisman H, Gibb J, Hayley S. Influence of continuous infusion of interleukin-1beta on depression-related processes in mice: corticosterone, circulating cytokines, brain monoamines, and cytokine mRNA expression. Psychopharmacology (Berl) 2008; 199(2):231–244CrossRefGoogle Scholar
  263. 263.
    Sawada M, Imamura K, Nagatsu T. Role of cytokines in inflammatory process in Parkinson’s disease. J Neural Transm Suppl 2006; (70):373–381Google Scholar
  264. 264.
    Perry VH, Cunningham C, Holmes C. Systemic infections and inflammation affect chronic neurodegeneration. Nat Rev Immunol 2007; 7(2):161–167PubMedCrossRefGoogle Scholar
  265. 265.
    Perry VH, Newman TA, Cunningham C. The impact of systemic infection on the progression of neurodegenerative disease. Nat Rev Neurosci 2003; 4(2):103–112PubMedCrossRefGoogle Scholar
  266. 266.
    Gao HM, Hong JS, Zhang W, et al. Synergistic dopaminergic neurotoxicity of the pesticide rotenone and inflammogen lipopolysaccharide: relevance to the etiology of Parkinson’s disease. J Neurosci 2003; 23(4):1228–1236PubMedGoogle Scholar
  267. 267.
    Gao HM, Liu B, Zhang W, et al. Critical role of microglial NADPH oxidase-derived free radicals in the in vitro MPTP model of Parkinson’s disease. FASEB J 2003; 17(13):1954–1956PubMedGoogle Scholar
  268. 268.
    Castano A, Herrera AJ, Cano J, et al. The degenerative effect of a single intranigral injection of LPS on the dopaminergic system is prevented by dexamethasone, and not mimicked by rh-TNF-alpha, IL-1beta and IFN-gamma. J Neurochem 2002; 81(1):150–157PubMedCrossRefGoogle Scholar
  269. 269.
    Ling Z, Zhu Y, Tong C, et al. Progressive dopamine neuron loss following supra-nigral lipopolysaccharide (LPS) infusion into rats exposed to LPS prenatally. Exp Neurol 2006; 199(2):499–512PubMedCrossRefGoogle Scholar
  270. 270.
    Barlow BK, Cory-Slechta DA, Richfield EK, et al. The gestational environment and Parkinson’s disease: evidence for neurodevelopmental origins of a neurodegenerative disorder. Reprod Toxicol 2007; 23(3):457–470PubMedCrossRefGoogle Scholar
  271. 271.
    Carvey PM, Chang Q, Lipton JW, et al. Prenatal exposure to the bacteriotoxin lipopolysaccharide leads to long-term losses of dopamine neurons in offspring: a potential, new model of Parkinson’s disease. Front Biosci 2003; 8:s826–s837PubMedCrossRefGoogle Scholar
  272. 272.
    Ling Z, Chang QA, Tong CW, et al. Rotenone potentiates dopamine neuron loss in animals exposed to lipopolysaccharide prenatally. Exp Neurol 2004; 190(2):373–383PubMedCrossRefGoogle Scholar
  273. 273.
    Dammann O, Leviton A. Infection remote from the brain, neonatal white matter damage, and cerebral palsy in the preterm infant. Semin Pediatr Neurol 1998; 5(3):190–201PubMedCrossRefGoogle Scholar
  274. 274.
    Ribiani E, Rosati A, Romanelli M, et al. Perinatal infections and cerebral palsy. Minerva Ginecol 200759(2):151–157Google Scholar
  275. 275.
    Hagberg H, Mallard C, Jacobsson B. Role of cytokines in preterm labour and brain injury. BJOG 2005; 112(Suppl 1):16–18PubMedCrossRefGoogle Scholar
  276. 276.
    Brustolim D, Ribeiro-dos-Santos R, Kast RE, et al. A new chapter opens in anti-inflammatory treatments: the antidepressant bupropion lowers production of tumor necrosis factor-alpha and interferon-gamma in mice. Int Immunopharmacol 2006; 6(6):903–907PubMedCrossRefGoogle Scholar
  277. 277.
    Zhu J, Mix E, Winblad B. The antidepressant and antiinflammatory effects of rolipram in the central nervous system. CNS Drug Rev 2001; 7(4):387–398PubMedCrossRefGoogle Scholar
  278. 278.
    Molina-Hernández M, Tellez-Alcántara NP, Pérez-García J, et al. Antidepressant-like actions of minocycline combined with several glutamate antagonists. Prog Neuropsychopharmacol Biol Psychiatry 2008; 32(2):380–386PubMedCrossRefGoogle Scholar
  279. 279.
    Benner EJ, Mosley RL, Destache CJ, et al. Therapeutic immunization protects dopaminergic neurons in a mouse model of Parkinson’s disease. Proc Natl Acad Sci USA 2004; 101(25):9435–9440PubMedCrossRefGoogle Scholar
  280. 280.
    Tsai SJ. Glatiramer acetate could be a potential antidepressant through its neuroprotective and anti-inflammatory effects. Med Hypotheses 2007; 69(1):145–148PubMedCrossRefGoogle Scholar
  281. 281.
    Kulmatycki KM, Jamali F. Drug disease interactions: role of inflammatory mediators in depression and variability in antidepressant drug response. J Pharm Pharm Sci 2006; 9(3):292–306PubMedGoogle Scholar
  282. 282.
    Chen H, Jacobs E, Schwarzschild MA, et al. Nonsteroidal antiinflammatory drug use and the risk for Parkinson’s disease. Ann Neurol 2005; 58(6):963–967PubMedCrossRefGoogle Scholar
  283. 283.
    Hernán MA, Logroscino G, García Rodríguez LA. Nonsteroidal anti-inflammatory drugs and the incidence of Parkinson disease. Neurology 2006; 66(7):1097–1099PubMedCrossRefGoogle Scholar
  284. 284.
    Wahner AD, Bronstein JM, Bordelon YM, et al. Nonsteroidal anti-inflammatory drugs may protect against Parkinson disease. Neurology 2007; 69(19):1836–1842PubMedCrossRefGoogle Scholar
  285. 285.
    Hayley S, Mangano E, Strickland M, et al. Lipopolysaccharide and a social stressor influence behaviour, corticosterone and cytokine levels: divergent actions in cyclooxygenase-2 deficient mice and wild type controls. J Neuroimmunol 2008; 197(1):29–36PubMedCrossRefGoogle Scholar
  286. 286.
    Kadhim HJ, Duchateau J, Sébire G. Cytokines and brain injury: invited review. J Intensive Care Med 2008; 23(4):236–249PubMedCrossRefGoogle Scholar
  287. 287.
    Basic Kes V, Simundic AM, Nikolac N, et al. Pro-inflammatory and anti-inflammatory cytokines in acute ischemic stroke and their relation to early neurological deficit and stroke outcome. Clin Biochem 2008; 41(16–17):1330–1334PubMedCrossRefGoogle Scholar
  288. 288.
    Bossù P, Ciaramella A, Salani F, et al. Interleukin-18 produced by peripheral blood cells is increased in Alzheimer’s disease and correlates with cognitive impairment. Brain Behav Immun 2008; 22(4):487–492PubMedCrossRefGoogle Scholar
  289. 289.
    Rohowsky-Kochan C, Molinaro D, Cook SD. Cytokine secretion profile of myelin basic protein-specific T cells in multiple sclerosis. Mult Scler 2000; 6(2):69–77PubMedGoogle Scholar
  290. 290.
    Goodman JC, Van M, Gopinath SP, et al. Pro-inflammatory and pro-apoptotic elements of the neuroinflammatory response are activated in traumatic brain injury. Acta Neurochir Suppl 2008; 102:437–439PubMedCrossRefGoogle Scholar
  291. 291.
    Barone FC, White RF, Spera PA, et al. Ischemic preconditioning and brain tolerance: temporal histological and functional outcomes, protein synthesis requirement, and interleukin-1 receptor antagonist and early gene expression. Stroke 1998; 29(9):1937–1950PubMedCrossRefGoogle Scholar
  292. 292.
    Bruce AJ, Boling W, Kindy MS, et al. Altered neuronal and microglial responses to excitotoxic and ischemic brain injury in mice lacking TNF receptors. Nat Med 1996; 2(7):788–794PubMedCrossRefGoogle Scholar
  293. 293.
    Hayley S, Poulter MO, Merali Z, et al. The pathogenesis of clinical depression: stressor- and cytokine-induced alterations of neuroplasticity. Neuroscience 2005; 135(3):659–678PubMedCrossRefGoogle Scholar
  294. 294.
    Vallières L, Campbell IL, Gage FH, et al. Reduced hippocampal neurogenesis in adult transgenic mice with chronic astrocytic production of interleukin-6. J Neurosci 2002; 22(2):486–492PubMedGoogle Scholar
  295. 295.
    Kaneko N, Kudo K, Mabuchi T, et al. Suppression of cell proliferation by interferon-alpha through interleukin-1 production in adult rat dentate gyrus. Neuropsychopharmacology 2006; 31(12):2619–2626PubMedCrossRefGoogle Scholar
  296. 296.
    Lee YJ, Choi B, Lee EH, et al. Immobilization stress induces cell death through production of reactive oxygen species in the mouse cerebral cortex. Neurosci Lett 2006; 392(1–2):27–31PubMedCrossRefGoogle Scholar
  297. 297.
    Chiou SH, Chen SJ, Peng CH, et al. Fluoxetine up-regulates expression of cellular FLICE-inhibitory protein and inhibits LPS-induced apoptosis in hippocampus-derived neural stem cell. Biochem Biophys Res Commun 2006; 343(2):391–400PubMedCrossRefGoogle Scholar
  298. 298.
    Monje ML, Toda H, Palmer TD. Inflammatory blockade restores adult hippocampal neurogenesis. Science 2003; 302(5651):1760–1765PubMedCrossRefGoogle Scholar
  299. 299.
    De Maeyer E, De Meyer-Guignard J. Interferons. In: Thomson AW (ed) The cytokine handbook, 3rd ed. Academic press, San Diego, CA, 1998; pp. 491–515Google Scholar
  300. 300.
    Ling LE, Zafari M, Reardon D, et al. Human type I interferon receptor, IFNAR, is a heavily glycosylated 120–130 kD membrane protein. J Interferon Cytokine Res 1995; 15(1):55–61PubMedCrossRefGoogle Scholar
  301. 301.
    Farrar MA, Fernandez-Luna J, Schreiber RD. Identification of two regions within the cytoplasmic domain of the human interferon-gamma receptor required for function. J Biol Chem 1991; 266(29):19626–19635PubMedGoogle Scholar
  302. 302.
    Briscoe J, Guschin D, Rogers NC, et al. JAKs, STATs and signal transduction in response to the interferons and other cytokines. Philos Trans R Soc Lond B Biol Sci 1996; 351(1336):167–171PubMedCrossRefGoogle Scholar
  303. 303.
    Kobayashi M, Fitz L, Ryan M, et al. Identification and purification of natural killer cell stimulatory factor (NKSF), a cytokine with multiple biologic effects on human lymphocytes. J Exp Med 1989; 170(3):827–845PubMedCrossRefGoogle Scholar
  304. 304.
    Issazadeh S, Mustafa M, Ljungdahl A, et al. Interferon gamma, interleukin 4 and transforming growth factor beta in experimental autoimmune encephalomyelitis in Lewis rats: dynamics of cellular mRNA expression in the central nervous system and lymphoid cells. J Neurosci Res 1995; 40(5):579–590PubMedCrossRefGoogle Scholar
  305. 305.
    Kawanokuchi J, Mizuno T, Takeuchi H, et al. Production of interferon-gamma by microglia. Mult Scler 2006; 12(5):558–564PubMedCrossRefGoogle Scholar
  306. 306.
    Shtrichman R, Samuel CE. The role of gamma interferon in antimicrobial immunity. Curr Opin Microbiol 2001; 4(3):251–259PubMedCrossRefGoogle Scholar
  307. 307.
    Philip R, Epstein LB. Tumour necrosis factor as immunomodulator and mediator of monocyte cytotoxicity induced by itself, gamma-interferon and interleukin-1. Nature 1986; 323(6083):86–89PubMedCrossRefGoogle Scholar
  308. 308.
    Gresser I. Wherefore interferon? J Leukoc Biol 1997; 61(5):567–574PubMedGoogle Scholar
  309. 309.
    Musselman DL, Lawson DH, Gumnick JF, et al. Paroxetine for the prevention of depression induced by high-dose interferon alfa. N Engl J Med 2001; 344(13):961–966PubMedCrossRefGoogle Scholar
  310. 310.
    Ishikawa J, Ishikawa A, Nakamura S. Interferon-alpha reduces the density of monoaminergic axons in the rat brain. Neuroreport 2007; 18(2):137–140PubMedCrossRefGoogle Scholar
  311. 311.
    Anisman H, Poulter MO, Gandhi R, et al. Interferon-alpha effects are exaggerated when administered on a psychosocial stressor backdrop: cytokine, corticosterone and brain monoamine variations. J Neuroimmunol 2007; 186(1–2):45–53PubMedCrossRefGoogle Scholar
  312. 312.
    Diamond M, Kelly JP, Connor TJ. Antidepressants suppress production of the Th1 cytokine interferon-gamma, independent of monoamine transporter blockade. Eur Neuropsychopharmacol 2006; 16(7):481–490PubMedCrossRefGoogle Scholar
  313. 313.
    Kubera M, Lin AH, Kenis G, et al. Anti-Inflammatory effects of antidepressants through suppression of the interferon-gamma/interleukin-10 production ratio. J Clin Psychopharmacol 2001; 21(2):199–206PubMedCrossRefGoogle Scholar
  314. 314.
    O’Connor JC, André C, Wang Y, et al. Interferon-gamma and tumor necrosis factor-alpha mediate the upregulation of indoleamine 2,3-dioxygenase and the induction of depressive-like behavior in mice in response to bacillus Calmette-Guerin. J Neurosci 2009; 29(13):4200–4209PubMedCrossRefGoogle Scholar
  315. 315.
    Menkes DB, MacDonald JA. Interferons, serotonin and neurotoxicity. Psychol Med 2000; 30:259–268PubMedCrossRefGoogle Scholar
  316. 316.
    Bonaccorso S, Puzella A, Marino V, et al. Immunotherapy with interferon-alpha in patients affected by chronic hepatitis C induces an intercorrelated stimulation of the cytokine network and an increase in depressive and anxiety symptoms. Psychiatry Res 2001; 105(1–2):45–55PubMedCrossRefGoogle Scholar
  317. 317.
    Bonaccorso S, Marino V, Puzella A, et al. Increased depressive ratings in patients with hepatitis C receiving interferon-alpha-based immunotherapy are related to interferon-alpha-induced changes in the serotonergic system. J Clin Psychopharmacol 2002; 22(1):86–90PubMedCrossRefGoogle Scholar
  318. 318.
    Wichers MC, Maes M. The role of indoleamine 2,3-dioxygenase (IDO) in the pathophysiology of interferon-alpha-induced depression. J. Psychiat Neurosci 2004; 29:11–17Google Scholar
  319. 319.
    Sarasombath P, Sumida K, Kaku DA. Parkinsonism associated with interferon alpha therapy for chronic myelogenous leukemia. Hawaii Med J 2002; 61(3):48–57PubMedGoogle Scholar
  320. 320.
    Mount MP, Lira A, Grimes D, et al. Involvement of interferon-gamma in microglial-mediated loss of dopaminergic neurons. J Neurosci 2007; 27(12):3328–3337PubMedCrossRefGoogle Scholar
  321. 321.
    Ciesielska A, Joniec I, Przybyłkowski A, et al. Dynamics of expression of the mRNA for cytokines and inducible nitric synthase in a murine model of the Parkinson’s disease. Acta Neurobiol Exp (Wars) 2003; 63(2):117–126Google Scholar
  322. 322.
    Ciesielska A, Joniec I, Kurkowska-Jastrzebska I, et al. Influence of age and gender on cytokine expression in a murine model of Parkinson’s disease. Neuroimmunomodulation 2007; 14(5):255–265PubMedCrossRefGoogle Scholar
  323. 323.
    Gribova IE, Gnedenko BB, Poleshchuk VV, et al. Level of interferon-gamma, tumor necrosis factor alpha, and antibodies to them in blood serum from Parkinson disease patients. Biomed Khim 2003; 49(2):208–212PubMedGoogle Scholar
  324. 324.
    Hunot S, Dugas N, Faucheux B, et al. FcepsilonRII/CD23 is expressed in Parkinson’s disease and induces, in vitro, production of nitric oxide and tumor necrosis factor-alpha in glial cells. J Neurosci 1999; 19(9):3440–3447PubMedGoogle Scholar
  325. 325.
    Mogi M, Kondo T, Mizuno Y, et al. p53 protein, interferon-gamma, and NF-kappaB levels are elevated in the parkinsonian brain. Neurosci Lett 2007; 414(1):94–97PubMedCrossRefGoogle Scholar
  326. 326.
    Mizuta I, Nishimura M, Mizuta E, et al. Relation between the high production related allele of the interferon-gamma (IFN-gamma) gene and age at onset of idiopathic Parkinson’s disease in Japan. J Neurol Neurosurg Psychiatry 2001; 71(6):818–819PubMedCrossRefGoogle Scholar
  327. 327.
    Yamada T, Horisberger MA, Kawaguchi N, et al. Immunohistochemistry using antibodies to alpha-interferon and its induced protein, MxA, in Alzheimer’s and Parkinson’s disease brain tissues. Neurosci Lett 1994; 181(1–2):61–64PubMedCrossRefGoogle Scholar
  328. 328.
    Widner B, Leblhuber F, Fuchs D. Increased neopterin production and tryptophan degradation in advanced Parkinson’s disease. J Neural Transm 2002; 109(2):181–189PubMedCrossRefGoogle Scholar
  329. 329.
    Członkowska A, Kurkowska-Jastrzebska I, Członkowski A, et al. Immune processes in the pathogenesis of Parkinson’s disease - a potential role for microglia and nitric oxide. Med Sci Monit 2002; 8(8):RA165–RA177PubMedGoogle Scholar
  330. 330.
    Mizuno T, Zhang G, Takeuchi H, et al. Interferon-gamma directly induces neurotoxicity through a neuron specific, calcium-permeable complex of IFN-gamma receptor and AMPA GluR1 receptor. FASEB J 2008; 22(6):1797–1806PubMedCrossRefGoogle Scholar
  331. 331.
    Moran LB, Duke DC, Graeber MB. The microglial gene regulatory network activated by interferon-gamma. J Neuroimmunol 2007; 183(1–2):1–6PubMedCrossRefGoogle Scholar
  332. 332.
    Wang X, Suzuki Y. Microglia produce IFN-gamma independently from T cells during acute toxoplasmosis in the brain. J Interferon Cytokine Res 2007; 27(7):599–605PubMedCrossRefGoogle Scholar
  333. 333.
    Schroder K, Hertzog PJ, Ravasi T, et al. Interferon-gamma: an overview of signals, mechanisms and functions. J Leukoc Biol 2004; 75(2):163–189PubMedCrossRefGoogle Scholar
  334. 334.
    Miklossy J, Qing H, Guo JP, et al. Lrrk2 and chronic inflammation are linked to pallido-ponto-nigral degeneration caused by the N279K tau mutation. Acta Neuropathol 2007; 114(3):243–254PubMedCrossRefGoogle Scholar
  335. 335.
    Yasuda T, Fukuda-Tani M, Nihira T, et al. Correlation between levels of pigment epithelium-derived factor and vascular endothelial growth factor in the striatum of patients with Parkinson’s disease. Exp Neurol 2007; 206(2):308–317PubMedCrossRefGoogle Scholar
  336. 336.
    Gupta JW, Kubin M, Hartman L, et al. Induction of expression of genes encoding components of the respiratory burst oxidase during differentiation of human myeloid cell lines induced by tumor necrosis factor and gamma-interferon. Cancer Res 1992; 52(9):2530–2537PubMedGoogle Scholar
  337. 337.
    Ramana CV, Grammatikakis N, Chernov M, et al. Regulation of c-myc expression by IFN-gamma through Stat1-dependent and -independent pathways. EMBO J 2000; 19(2):263–272PubMedCrossRefGoogle Scholar
  338. 338.
    Mir M, Tolosa L, Asensio VJ, et al. Complementary roles of tumor necrosis factor alpha and interferon gamma in inducible microglial nitric oxide generation. J Neuroimmunol 2008; 204(1–2):101–109PubMedCrossRefGoogle Scholar
  339. 339.
    Zamanian-Daryoush M, Mogensen TH, DiDonato JA, et al. NF-kappaB activation by double-stranded-RNA-activated protein kinase (PKR) is mediated through NF-kappaB-inducing kinase and IkappaB kinase. Mol Cell Biol 2000; 20(4):1278–1290PubMedCrossRefGoogle Scholar
  340. 340.
    Esposito E, Iacono A, Muià C, et al. Signal transduction pathways involved in protective effects of melatonin in C6 glioma cells. J Pineal Res 2008; 44(1):78–87PubMedGoogle Scholar
  341. 341.
    Baba Y, Kuroiwa A, Uitti RJ, et al. Alterations of T-lymphocyte populations in Parkinson disease. Parkinsonism Relat Disord 2005; 11(8):493–498PubMedCrossRefGoogle Scholar
  342. 342.
    Durbin J, Doughty L, Nguyen K, et al. The role of STAT1 in viral sensitization to LPS. J Endotoxin Res 2003; 9(5):313–316PubMedGoogle Scholar
  343. 343.
    Kato T, Monji A, Hashioka S, et al. Risperidone significantly inhibits interferon-gamma-induced microglial activation in vitro. Schizophr Res 2007; 92(1–3):108–115PubMedCrossRefGoogle Scholar
  344. 344.
    Nansen A, Christensen JP, Marker O, et al. Sensitization to lipopolysaccharide in mice with asymptomatic viral infection: role of T cell-dependent production of interferon-gamma. J Infect Dis 1997; 176(1):151–157PubMedCrossRefGoogle Scholar
  345. 345.
    Doyle KP, Yang T, Lessov NS, et al. Nasal administration of osteopontin peptide mimetics confers neuroprotection in stroke. J Cereb Blood Flow Metab 2008; 28(6):1235–1248PubMedCrossRefGoogle Scholar
  346. 346.
    Meller R, Stevens SL, Minami M, et al. Neuroprotection by osteopontin in stroke. J Cereb Blood Flow Metab 2005; 25(2):217–225PubMedCrossRefGoogle Scholar
  347. 347.
    Iczkiewicz J, Jackson MJ, Smith LA, et al. Osteopontin expression in substantia nigra in MPTP-treated primates and in Parkinson’s disease. Brain Res 2006; 1118(1):239–250PubMedCrossRefGoogle Scholar
  348. 348.
    Thornberry NA, Bull HG, Calaycay JR, et al. A novel heterodimeric cysteine protease is required for interleukin-1 beta processing in monocytes. Nature 1992; 356(6372):768–774PubMedCrossRefGoogle Scholar
  349. 349.
    Dinarello CA. Biology of interleukin 1. FASEB J 1988; 2(2):108–115PubMedGoogle Scholar
  350. 350.
    Plata-Salamán CR. Meal patterns in response to the intracerebroventricular administration of interleukin-1 beta in rats. Physiol Behav 1994; 55(4):727–733PubMedCrossRefGoogle Scholar
  351. 351.
    Bennani-Baiti N, Davis MP. Cytokines and cancer anorexia cachexia syndrome. Am J Hosp Palliat Care 2008; 25(5):407–411PubMedCrossRefGoogle Scholar
  352. 352.
    Eigler A, Sinha B, Hartmann G, et al. Taming TNF: strategies to restrain this proinflammatory cytokine. Immunol Today 1997; 18(10):487–492PubMedCrossRefGoogle Scholar
  353. 353.
    Nagatsu T, Mogi M, Ichinose H, et al. Changes in cytokines and neurotrophins in Parkinson’s disease. J Neural Transm Suppl 2000; 60: 277–290PubMedGoogle Scholar
  354. 354.
    Mandel S, Grünblatt E, Youdim M. cDNA microarray to study gene expression of dopaminergic neurodegeneration and neuroprotection in MPTP and 6-hydroxydopamine models: implications for idiopathic Parkinson’s disease. J Neural Transm Suppl 2000; (60):117–124Google Scholar
  355. 355.
    Hébert G, Arsaut J, Dantzer R, et al. Time-course of the expression of inflammatory cytokines and matrix metalloproteinases in the striatum and mesencephalon of mice injected with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, a dopaminergic neurotoxin. Neurosci Lett 2003; 349(3):191–195PubMedCrossRefGoogle Scholar
  356. 356.
    Jin F, Wu Q, Lu YF, et al. Neuroprotective effect of resveratrol on 6-OHDA-induced Parkinson’s disease in rats. Eur J Pharmacol 2008; 600(1–3):78–82PubMedCrossRefGoogle Scholar
  357. 357.
    Saura J, Pares M, Bove J, et al. Intranigral infusion of interleukin-1beta activates astrocytes and protects from subsequent 6-hydroxydopamine neurotoxicity. J Neurochem 2003; 85(3):651–661PubMedCrossRefGoogle Scholar
  358. 358.
    Wang J, Bankiewicz KS, Plunkett RJ, et al. Intrastriatal implantation of interleukin-1. Reduction of parkinsonism in rats by enhancing neuronal sprouting from residual dopaminergic neurons in the ventral tegmental area of the midbrain. J Neurosurg 1994; 80(3):484–490PubMedCrossRefGoogle Scholar
  359. 359.
    Bolin LM, Strycharska-Orczyk I, Murray R, et al. Increased vulnerability of dopaminergic neurons in MPTP-lesioned interleukin-6 deficient mice. J Neurochem 2002; 83(1):167–175PubMedCrossRefGoogle Scholar
  360. 360.
    Ferger B, Leng A, Mura A, et al. Genetic ablation of tumor necrosis factor-alpha (TNF-alpha) and pharmacological inhibition of TNF-synthesis attenuates MPTP toxicity in mouse striatum. J Neurochem 2004; 89(4):822–833PubMedCrossRefGoogle Scholar
  361. 361.
    Sriram K, Matheson JM, Benkovic SA, et al. Mice deficient in TNF receptors are protected against dopaminergic neurotoxicity: implications for Parkinson’s disease. FASEB 2002; 16(11):1474–1476Google Scholar
  362. 362.
    Rousselet E, Callebert J, Parain K, et al. Role of TNF-alpha receptors in mice intoxicated with the parkinsonian toxin MPTP. Exp Neurol 2002; 177(1):183–192PubMedCrossRefGoogle Scholar
  363. 363.
    Dantzer R. Cytokine, sickness behavior, and depression. Neurol Clin 2006; 24(3):441–460PubMedCrossRefGoogle Scholar
  364. 364.
    Dantzer R. Cytokine-induced sickness behavior: mechanisms and implications. Ann NY Acad Sci 2001; 933:222–234PubMedCrossRefGoogle Scholar
  365. 365.
    Anisman H, Kokkinidis L, Borowski T, et al. Differential effects of interleukin (IL)-1beta, IL-2 and IL-6 on responding for rewarding lateral hypothalamic stimulation. Brain Res 1998; 779(1–2):177–187PubMedCrossRefGoogle Scholar
  366. 366.
    Merali Z, Brennan K, Brau P, et al. Dissociating anorexia and anhedonia elicited by interleukin-1beta: antidepressant and gender effects on responding for “free chow” and “earned” sucrose intake. Psychopharmacology (Berl) 2003; 165(4):413–418Google Scholar
  367. 367.
    Bluthé RM, Dantzer R, Kelley KW. Central mediation of the effects of interleukin-1 on social exploration and body weight in mice. Psychoneuroendocrinology 1997; 22(1):1–11PubMedCrossRefGoogle Scholar
  368. 368.
    Gibertini M, Newton C, Friedman H, et al. Spatial learning impairment in mice infected with Legionella pneumophila or administered exogenous interleukin-1-beta. Brain Behav Immun. 1995; 9(2):113–128PubMedCrossRefGoogle Scholar
  369. 369.
    Lucas PC, McAllister-Lucas LM, Nunez G. NF-kappaB signaling in lymphocytes: a new cast of characters. J Cell Sci 2004; 117(Pt 1):31–39PubMedCrossRefGoogle Scholar
  370. 370.
    Poynter ME, Cloots R, van Woerkom T, et al. NF-kappa B activation in airways modulates allergic inflammation but not hyperresponsiveness. J Immunol 2004; 173(11):7003–7009PubMedGoogle Scholar
  371. 371.
    Konsman JP, Tridon V, Dantzer R. Diffusion and action of intracerebroventricularly injected interleukin-1 in the CNS. Neuroscience 2000; 101(4):957–967PubMedCrossRefGoogle Scholar
  372. 372.
    Mattson MP. NF-kappaB in the survival and plasticity of neurons. Neurochem Res 2005; 30(6–7):883–893PubMedCrossRefGoogle Scholar
  373. 373.
    Kassed CA, Butler TL, Patton GW, et al. Injury-induced NF-kappaB activation in the hippocampus: implications for neuronal survival. FASEB J 2004; 18(6):723–724PubMedGoogle Scholar
  374. 374.
    Freudenthal R, Romano A, Routtenberg A. Transcription factor NF-kappaB activation after in vivo perforant path LTP in mouse hippocampus. Hippocampus 2004; 14(6):677–683PubMedCrossRefGoogle Scholar
  375. 375.
    Aoki E, Yano R, Yokoyama H, et al. Role of nuclear transcription factor kappa B (NF-kappaB) for MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahyropyridine)-induced apoptosis in nigral neurons of mice. Exp Mol Pathol 2009; 86(1):57–64PubMedCrossRefGoogle Scholar
  376. 376.
    Pahan K, Sheikh FG, Liu X, et al. Induction of nitric-oxide synthase and activation of NF-kappaB by interleukin-12 p40 in microglial cells. J Biol Chem 2001; 276(11):7899–7905PubMedCrossRefGoogle Scholar
  377. 377.
    Hartlage-Rübsamen M, Lemke R, Schliebs R. Interleukin-1beta, inducible nitric oxide synthase, and nuclear factor-kappaB are induced in morphologically distinct microglia after rat hippocampal lipopolysaccharide/interferon-gamma injection. J Neurosci Res 1999; 57(3):388–398PubMedCrossRefGoogle Scholar
  378. 378.
    Madrigal JL, García-Bueno B, Caso JR, et al. Stress-induced oxidative changes in brain. CNS Neurol Disord Drug Targets 2006; 5(5):561–568PubMedCrossRefGoogle Scholar
  379. 379.
    D’Aversa TG, Eugenin EA, Berman JW. CD40-CD40 ligand interactions in human microglia induce CXCL8 (interleukin-8) secretion by a mechanism dependent on activation of ERK1/2 and nuclear translocation of nuclear factor-kappaB (NFkappaB) and activator protein-1 (AP-1). J Neurosci Res 2008; 86(3):630–639PubMedCrossRefGoogle Scholar
  380. 380.
    Bethea CL, Reddy AP, Smith LJ. Nuclear factor kappa B in the dorsal raphe of macaques: an anatomical link for steroids, cytokines and serotonin. J Psychiatry Neurosci 2006; 31(2):105–114PubMedGoogle Scholar
  381. 381.
    Nadjar A, Bluthé RM, May MJ, et al. Inactivation of the cerebral NFkappaB pathway inhibits interleukin-1beta-induced sickness behavior and c-Fos expression in various brain nuclei. Neuropsychopharmacology 2005; 30(8):1492–1499PubMedCrossRefGoogle Scholar
  382. 382.
    Kassed CA, Herkenham M. NF-kappaB p50-deficient mice show reduced anxiety-like behaviors in tests of exploratory drive and anxiety. Behav Brain Res 2004; 154(2):577–584PubMedCrossRefGoogle Scholar
  383. 383.
    Spiliotaki M, Salpeas V, Malitas P, et al. Altered glucocorticoid receptor signaling cascade in lymphocytes of bipolar disorder patients. Psychoneuroendocrinology 2006; 31(6):748–760PubMedCrossRefGoogle Scholar
  384. 384.
    Nagabhushan M, Mathews HL, Witek-Janusek L. Aberrant nuclear expression of AP-1 and NFkappaB in lymphocytes of women stressed by the experience of breast biopsy. Brain Behav Immun 2001; 15(1):78–84PubMedCrossRefGoogle Scholar
  385. 385.
    Barger SW, Moerman AM, Mao X. Molecular mechanisms of cytokine-induced neuroprotection: NFkappaB and neuroplasticity. Curr Pharm Des 2005; 11(8):985–998PubMedCrossRefGoogle Scholar
  386. 386.
    Hong S, Gronert K, Devchand PR, et al. Novel docosatrienes and 17S-resolvins generated from docosahexaenoic acid in murine brain, human blood, and glial cells. Autacoids in anti-inflammation. J Biol Chem 2003; 278(17):14677–14687PubMedCrossRefGoogle Scholar
  387. 387.
    Manabe Y, Anrather J, Kawano T, et al. Prostanoids, not reactive oxygen species, mediate COX-2-dependent neurotoxicity. Ann Neurol 2004; 55(5):668–675PubMedCrossRefGoogle Scholar
  388. 388.
    Tzeng SF, Hsiao HY, Mak OT. Prostaglandins and cyclooxygenases in glial cells during brain inflammation. Curr Drug Targets Inflamm Allergy 2005; 4(3):335–340PubMedCrossRefGoogle Scholar
  389. 389.
    Knott C, Stern G, Wilkin GP. Inflammatory regulators in Parkinson’s disease: iNOS, lipocortin-1, and cyclooxygenases-1 and -2. Mol Cell Neurosci 2000; 16(6):724–739PubMedCrossRefGoogle Scholar
  390. 390.
    Teismann P, Tieu K, Choi DK, et al. Cyclooxygenase-2 is instrumental in Parkinson’s disease neurodegeneration. Proc Natl Acad Sci USA 2003; 100(9):5473–5478PubMedCrossRefGoogle Scholar
  391. 391.
    Sánchez-Pernaute R, Ferree A, Cooper O, et al. Selective COX-2 inhibition prevents progressive dopamine neuron degeneration in a rat model of Parkinson’s disease. J Neuroinflammation 2004; 1(1):6–14PubMedCrossRefGoogle Scholar
  392. 392.
    Wang T, Pei Z, Zhang W, et al. MPP+-induced COX-2 activation and subsequent dopaminergic neurodegeneration. FASEB J 2005; 19(9):1134–1136PubMedGoogle Scholar
  393. 393.
    Vijitruth R, Liu M, Choi DY, et al. Cyclooxygenase-2 mediates microglial activation and secondary dopaminergic cell death in the mouse MPTP model of Parkinson’s disease. J Neuroinflammation 2006; 3:6–21PubMedCrossRefGoogle Scholar
  394. 394.
    Feng ZH, Wang TG, Li DD, et al. Cyclooxygenase-2-deficient mice are resistant to 1-methyl-4-phenyl1, 2, 3, 6-tetrahydropyridine-induced damage of dopaminergic neurons in the substantia nigra. Neurosci Lett 2002; 329(3):354–358PubMedCrossRefGoogle Scholar
  395. 395.
    Esposito E, Di Matteo V, Benigno A, et al. Non-steroidal anti-inflammatory drugs in Parkinson’s disease. Exp Neurol 2007; 205(2):295–312PubMedCrossRefGoogle Scholar
  396. 396.
    Kawano T, Anrather J, Zhou P, et al. Prostaglandin E2 EP1 receptors: downstream effectors of COX-2 neurotoxicity. Nat Med 2006; 12(2):225–229PubMedCrossRefGoogle Scholar
  397. 397.
    Carrasco E, Casper D, Werner P. PGE(2) receptor EP1 renders dopaminergic neurons selectively vulnerable to low-level oxidative stress and direct PGE(2) neurotoxicity. J Neurosci Res 2007; 85(14):3109–3117PubMedCrossRefGoogle Scholar
  398. 398.
    Takadera T, Ohyashiki T. Prevention of rat cortical neurons from prostaglandin E2-induced apoptosis by glycogen synthase kinase-3 inhibitors. Neurosci Lett 2006; 400(1–2):105–109PubMedCrossRefGoogle Scholar
  399. 399.
    Takadera T, Yumoto H, Tozuka Y, et al. Prostaglandin E(2) induces caspase-dependent apoptosis in rat cortical cells. Neurosci Lett 2002; 317(2):61–64PubMedCrossRefGoogle Scholar
  400. 400.
    Dumont I, Peri KG, Hardy P, et al. PGE2, via EP3 receptors, regulates brain nitric oxide synthase in the perinatal period. Am J Physiol 1998; 275(6 Pt 2):R1812–R1821PubMedGoogle Scholar
  401. 401.
    Shie FS, Montine KS, Breyer RM, et al. Microglial EP2 is critical to neurotoxicity from activated cerebral innate immunity. Glia 2005; 52(1):70–77PubMedCrossRefGoogle Scholar
  402. 402.
    Toscano CD, Prabhu VV, Langenbach R, et al. Differential gene expression patterns in cyclooxygenase-1 and cyclooxygenase-2 deficient mouse brain. Genome Biol 2007; 8(1):R14PubMedCrossRefGoogle Scholar
  403. 403.
    Vichai V, Suyarnsesthakorn C, Pittayakhajonwut D, et al. Positive feedback regulation of COX-2 expression by prostaglandin metabolites. Inflamm Res 2005; 54(4):163–172PubMedCrossRefGoogle Scholar
  404. 404.
    Nadjar A, Tridon V, May MJ, et al. NFkappaB activates in vivo the synthesis of inducible Cox-2 in the brain. J Cereb Blood Flow Metab 2005; 25(8):1047–1059PubMedCrossRefGoogle Scholar
  405. 405.
    Hunot S, Brugg B, Ricard D, et al. Nuclear translocation of NF-kappaB is increased in dopaminergic neurons of patients with parkinson disease. Proc Natl Acad Sci USA 1997; 94(14):7531–7536PubMedCrossRefGoogle Scholar
  406. 406.
    Bazan NG, Colangelo V, Lukiw WJ. Prostaglandins and other lipid mediators in Alzheimer’s disease. Prostaglandins Other Lipid Mediat 2002; 68–69:197–210PubMedCrossRefGoogle Scholar
  407. 407.
    Hastings TG. Enzymatic oxidation of dopamine: the role of prostaglandin H synthase. J Neurochem 1995; 64(2):919–924PubMedCrossRefGoogle Scholar
  408. 408.
    LaVoie MJ, Hastings TG. Peroxynitrite- and nitrite-induced oxidation of dopamine: implications for nitric oxide in dopaminergic cell loss. J Neurochem 1999; 73(6):2546–2554PubMedCrossRefGoogle Scholar
  409. 409.
    Ahmad AS, Zhuang H, Echeverria V, et al. Stimulation of prostaglandin EP2 receptors prevents NMDA-induced excitotoxicity. J Neurotrauma 2006; 23(12):1895–1903PubMedCrossRefGoogle Scholar
  410. 410.
    Echeverria V, Clerman A, Doré S. Stimulation of PGE receptors EP2 and EP4 protects cultured neurons against oxidative stress and cell death following beta-amyloid exposure. Eur J Neurosci 2005; 22(9):2199–2206PubMedCrossRefGoogle Scholar
  411. 411.
    Levi G, Minghetti L, Aloisi F. Regulation of prostanoid synthesis in microglial cells and effects of prostaglandin E2 on microglial functions. Biochimie 1998; 80(11):899–904PubMedCrossRefGoogle Scholar
  412. 412.
    Lee EO, Shin YJ, Chong YH. Mechanisms involved in prostaglandin E2-mediated neuroprotection against TNF-alpha: possible involvement of multiple signal transduction and beta-catenin/T-cell factor. J Neuroimmunol 2004; 155(1–2):21–31PubMedCrossRefGoogle Scholar
  413. 413.
    Bulló M, Peeraully MR, Trayhurn P. Stimulation of NGF expression and secretion in 3T3-L1 adipocytes by prostaglandins PGD2, PGJ2, and Delta12-PGJ2. Am J Physiol Endocrinol Metab 2005; 289(1):E62–E67PubMedCrossRefGoogle Scholar
  414. 414.
    Marcheselli VL, Hong S, Lukiw WJ, et al. Novel docosanoids inhibit brain ischemia-reperfusion-mediated leukocyte infiltration and pro-inflammatory gene expression. J Biol Chem 2003; 278(44):43807–43817PubMedCrossRefGoogle Scholar
  415. 415.
    Mukherjee PK, Marcheselli VL, Serhan CN, et al. Neuroprotectin D1: a docosahexaenoic acid-derived docosatriene protects human retinal pigment epithelial cells from oxidative stress. Proc Natl Acad Sci U S A 2004; 101(22):8491–8496PubMedCrossRefGoogle Scholar
  416. 416.
    Bazan NG, Marcheselli VL, Cole-Edwards K. Brain response to injury and neurodegeneration: endogenous neuroprotective signaling. Ann NY Acad Sci 2005; 1053:137–147PubMedCrossRefGoogle Scholar
  417. 417.
    Calabrese JR, Skwerer RG, Barna B, et al. Depression, immunocompetence, and prostaglandins of the E series. Psychiatry Res 1986; 17(1):41–47PubMedCrossRefGoogle Scholar
  418. 418.
    Ohishi K, Ueno R, Nishino S, et al. Increased level of salivary prostaglandins in patients with major depression. Biol Psychiatry 1988; 23(4):326–334PubMedCrossRefGoogle Scholar
  419. 419.
    Nishino S, Ueno R, Ohishi K, et al. Salivary prostaglandin concentrations: possible state indicators for major depression. Am J Psychiatry 1989; 146(3):365–368PubMedGoogle Scholar
  420. 420.
    Song C, Lin A, Bonaccorso S, et al. The inflammatory response system and the availability of plasma tryptophan in patients with primary sleep disorders and major depression. J Affect Disord 1998; 49(3):211–219PubMedCrossRefGoogle Scholar
  421. 421.
    Collantes-Estevez E, Fernandez-Perez C. Improved control of osteoarthritis pain and self-reported health status in non-responders to celecoxib switched to rofecoxib: results of PAVIA, an open-label post-marketing survey in Spain. Curr Med Res Opin 2003; 19(5):402–410PubMedCrossRefGoogle Scholar
  422. 422.
    Nery FG, Monkul ES, Hatch JP, et al. Celecoxib as an adjunct in the treatment of depressive or mixed episodes of bipolar disorder: a double-blind, randomized, placebo-controlled study. Hum Psychopharmacol 2008; 23(2):87–94PubMedCrossRefGoogle Scholar
  423. 423.
    Mtabaji JP, Manku MS, Horrobin DF. Actions of the tricyclic antidepressant clomipramine on responses to pressor agents. Interactions with prostaglandin E2. Prostaglandins 1977; 14(1):125–132Google Scholar
  424. 424.
    Yaron I, Shirazi I, Judovich R, et al. Fluoxetine and amitriptyline inhibit nitric oxide, prostaglandin E2, and hyaluronic acid production in human synovial cells and synovial tissue cultures. Arthritis Rheum 1999; 42(12):2561–2568PubMedCrossRefGoogle Scholar
  425. 425.
    Myint AM, Steinbusch HW, Goeghegan L, et al. Effect of the COX-2 inhibitor celecoxib on behavioural and immune changes in an olfactory bulbectomised rat model of depression. Neuroimmunomodulation 2007; 14(2):65–71PubMedCrossRefGoogle Scholar
  426. 426.
    De La Garza R 2nd, Asnis GM. The non-steroidal anti-inflammatory drug diclofenac sodium attenuates IFN-alpha induced alterations to monoamine turnover in prefrontal cortex and hippocampus. Brain Res 2003; 977(1):70–79PubMedCrossRefGoogle Scholar
  427. 427.
    Linthorst AC, Flachskamm C, Holsboer F, et al. Activation of serotonergic and noradrenergic neurotransmission in the rat hippocampus after peripheral administration of bacterial endotoxin: involvement of the cyclo-oxygenase pathway. Neuroscience 1996; 72(4):989–997PubMedCrossRefGoogle Scholar
  428. 428.
    Li S, Ballou LR, Morham SG, et al. Cyclooxygenase-2 mediates the febrile response of mice to interleukin-1beta. Brain Res 2001; 910(1–2):163–173PubMedCrossRefGoogle Scholar
  429. 429.
    Li S, Wang Y, Matsumura K, et al. The febrile response to lipopolysaccharide is blocked in cyclooxygenase-2(–/–), but not in cyclooxygenase-1(–/–) mice. Brain Res 1999; 825(1–2):86–94PubMedCrossRefGoogle Scholar
  430. 430.
    Madrigal JL, Moro MA, Lizasoain I, et al. Induction of cyclooxygenase-2 accounts for restraint stress-induced oxidative status in rat brain. Neuropsychopharmacology 2003; 28(9):1579–1588PubMedCrossRefGoogle Scholar
  431. 431.
    Dhir A, Padi SS, Naidu PS, et al. Protective effect of naproxen (non-selective COX-inhibitor) or rofecoxib (selective COX-2 inhibitor) on immobilization stress-induced behavioral and biochemical alterations in mice. Eur J Pharmacol 2006; 535(1–3):192–198PubMedCrossRefGoogle Scholar
  432. 432.
    Kumari B, Kumar A, Dhir A. Protective effect of non-selective and selective COX-2-inhibitors in acute immobilization stress-induced behavioral and biochemical alterations Pharmacol Rep 2007; 59(6):699–707Google Scholar
  433. 433.
    Guo JY, Li CY, Ruan YP, et al. Chronic treatment with celecoxib reverses chronic unpredictable stress-induced depressive-like behavior via reducing cyclooxygenase-2 expression in rat brain. Eur J Pharmacol 2009; 612(1–3):54–60PubMedCrossRefGoogle Scholar
  434. 434.
    Ownby RL, Crocco E, Acevedo A, et al. Depression and risk for Alzheimer disease: systematic review, meta-analysis, and metaregression analysis. Arch Gen Psychiatry 2006; 63(5):530–538PubMedCrossRefGoogle Scholar
  435. 435.
    Palmer K, Berger AK, Monastero R, et al. Predictors of progression from mild cognitive impairment to Alzheimer disease. Neurology 2007; 68(19):1596–1602PubMedCrossRefGoogle Scholar
  436. 436.
    Starkstein SE, Jorge R, Petracca G, et al. The construct of generalized anxiety disorder in Alzheimer disease. Am J Geriatr Psychiatry 2007; 15(1):42–49PubMedCrossRefGoogle Scholar
  437. 437.
    Meynen G, Unmehopa UA, Hofman MA, et al. Relation between corticotropin-releasing hormone neuron number in the hypothalamic paraventricular nucleus and depressive state in Alzheimer’s disease. Neuroendocrinology 2007; 85(1):37–44PubMedCrossRefGoogle Scholar
  438. 438.
    Raadsheer FC, Hoogendijk WJ, Stam FC, et al. Increased numbers of corticotropin-releasing hormone expressing neurons in the hypothalamic paraventricular nucleus of depressed patients. Neuroendocrinology 1994; 60(4):436–444PubMedCrossRefGoogle Scholar
  439. 439.
    Engelborghs S, De Deyn PP. The neurochemistry of Alzheimer’s disease. Acta Neurol Belg 1997; 97(2):67–84PubMedGoogle Scholar
  440. 440.
    Nelson RL, Guo Z, Halagappa VM, et al. Prophylactic treatment with paroxetine ameliorates behavioral deficits and retards the development of amyloid and tau pathologies in 3xTgAD mice. Exp Neurol 2007; 205(1):166–176PubMedCrossRefGoogle Scholar
  441. 441.
    Kuipers SD, Bramham CR. Brain-derived neurotrophic factor mechanisms and function in adult synaptic plasticity: new insights and implications for therapy. Curr Opin Drug Discov Devel 2006; 9(5):580–586PubMedGoogle Scholar
  442. 442.
    Hussain AM, Mitra AK. Effect of aging on tryptophan hydroxylase in rat brain: implications on serotonin level. Drug Metab Dispos 2000; 28(9):1038–1042PubMedGoogle Scholar
  443. 443.
    Melnikova T, Savonenko A, Wang Q, et al. Cycloxygenase-2 activity promotes cognitive deficits but not increased amyloid burden in a model of Alzheimer’s disease in a sex-dimorphic pattern. Neuroscience 2006; 141(3):1149–1162PubMedCrossRefGoogle Scholar
  444. 444.
    Liang X, Wang Q, Hand T, et al. Deletion of the prostaglandin E2 EP2 receptor reduces oxidative damage and amyloid burden in a model of Alzheimer’s disease. J Neurosci 2005; 25(44):10180–10187PubMedCrossRefGoogle Scholar
  445. 445.
    Müller N, Riedel M, Schwarz MJ. Psychotropic effects of COX-2 inhibitors – a possible new approach for the treatment of psychiatric disorders. Pharmacopsychiatry 2004; 37(6):266–269PubMedCrossRefGoogle Scholar
  446. 446.
    Cotter RL, Burke WJ, Thomas VS, et al. Insights into the neurodegenerative process of Alzheimer’s disease: a role for mononuclear phagocyte-associated inflammation and neurotoxicity. J Leukoc Biol 1999; 65(4):416–427PubMedGoogle Scholar
  447. 447.
    Eikelenboom P, Veerhuis R, Scheper W, et al. The significance of neuroinflammation in understanding Alzheimer’s disease. J Neural Transm 2006; 113(11):1685–1695PubMedCrossRefGoogle Scholar
  448. 448.
    Haga S, Akai K, Ishii T. Demonstration of microglial cells in and around senile (neuritic) plaques in the Alzheimer brain. An immunohistochemical study using a novel monoclonal antibody. Acta Neuropathol 1989; 77(6):569–575PubMedCrossRefGoogle Scholar
  449. 449.
    Chiarini A, Dal Pra I, Menapace L, et al. Soluble amyloid beta-peptide and myelin basic protein strongly stimulate, alone and in synergism with combined proinflammatory cytokines, the expression of functional nitric oxide synthase-2 in normal adult human astrocytes. Int J Mol Med 2005; 16(5):801–807PubMedGoogle Scholar
  450. 450.
    Sheng JG, Mrak RE, Griffin WS. Glial-neuronal interactions in Alzheimer disease: progressive association of IL-1alpha+ microglia and S100beta+ astrocytes with neurofibrillary tangle stages. J Neuropathol Exp Neurol 1997; 56(3):285–220Google Scholar
  451. 451.
    Ding Q, Dimayuga E, Keller JN. Oxidative damage, protein synthesis, and protein degradation in Alzheimer’s disease. Curr Alzheimer Res 2007; 4(1):73–79PubMedCrossRefGoogle Scholar
  452. 452.
    Liu L, Li Y, Van Eldik LJ, et al. S100B-induced microglial and neuronal IL-1 expression is mediated by cell type-specific transcription factors. J Neurochem 2005; 92(3):546–553PubMedCrossRefGoogle Scholar
  453. 453.
    Griffin WS, Liu L, Li Y, et al. Interleukin-1 mediates Alzheimer and Lewy body pathologies. J Neuroinflammation. 2006; 3:5PubMedCrossRefGoogle Scholar
  454. 454.
    Yamamoto M, Kiyota T, Horiba M, et al. Interferon-gamma and tumor necrosis factor-alpha regulate amyloid-beta plaque deposition and beta-secretase expression in Swedish mutant APP transgenic mice. Am J Pathol 2007; 170(2):680–692PubMedCrossRefGoogle Scholar
  455. 455.
    Tong L, Balazs R, Soiampornkul R, et al. Interleukin-1 beta impairs brain derived neurotrophic factor-induced signal transduction. Neurobiol Aging 2008; 29(9):1380–1393PubMedCrossRefGoogle Scholar
  456. 456.
    Orellana DI, Quintanilla RA, Maccioni RB. Neuroprotective effect of TNFalpha against the beta-amyloid neurotoxicity mediated by CDK5 kinase. Biochim Biophys Acta 2007; 1773(2):254–263PubMedCrossRefGoogle Scholar
  457. 457.
    Li R, Yang L, Lindholm K, et al. Tumor necrosis factor death receptor signaling cascade is required for amyloid-beta protein-induced neuron death. J Neurosci 2004; 24(7):1760–1771PubMedCrossRefGoogle Scholar
  458. 458.
    Dopp JM, Sarafian TA, Spinella FM, et al. Expression of the p75 TNF receptor is linked to TNF-induced NFkappaB translocation and oxyradical neutralization in glial cells. Neurochem Res 2002; 27(11):1535–1542PubMedCrossRefGoogle Scholar
  459. 459.
    Neta R, Sayers TJ, Oppenheim JJ. Relationship of TNF to interleukins. Immunol Ser 1992; 56:499–566PubMedGoogle Scholar
  460. 460.
    Fernyhough P, Smith DR, Schapansky J, et al. Activation of nuclear factor-kappaB via endogenous tumor necrosis factor alpha regulates survival of axotomized adult sensory neurons. J Neurosci 2005; 25(7):1682–1690PubMedCrossRefGoogle Scholar
  461. 461.
    Takeuchi H, Jin S, Wang J, et al. Tumor necrosis factor-alpha induces neurotoxicity via glutamate release from hemichannels of activated microglia in an autocrine manner. J Biol Chem 2006; 281(30):21362–21368PubMedCrossRefGoogle Scholar
  462. 462.
    Alvarez XA, Franco A, Fernández-Novoa L, et al. Blood levels of histamine, IL-1 beta, and TNF-alpha in patients with mild to moderate Alzheimer disease. Mol Chem Neuropathol 1996; 29(2–3):237–252PubMedCrossRefGoogle Scholar
  463. 463.
    Magaki S, Mueller C, Dickson C, et al. Increased production of inflammatory cytokines in mild cognitive impairment. Exp Gerontol 2007; 42(3):233–240PubMedCrossRefGoogle Scholar
  464. 464.
    Alvarez A, Cacabelos R, Sanpedro C, et al. Serum TNF-alpha levels are increased and correlate negatively with free IGF-I in Alzheimer disease. Neurobiol Aging 2007; 28(4):533–536PubMedCrossRefGoogle Scholar
  465. 465.
    Bagnoli S, Cellini E, Tedde A, et al. Association of IL10 promoter polymorphism in Italian Alzheimer’s disease. Neurosci Lett 2007; 418(3):262–265PubMedCrossRefGoogle Scholar
  466. 466.
    Bossù P, Ciaramella A, Moro ML, et al. Interleukin 18 gene polymorphisms predict risk and outcome of Alzheimer’s disease. J Neurol Neurosurg Psychiatry 2007; 78(8):807–811PubMedCrossRefGoogle Scholar
  467. 467.
    McCulley MC, Day IN, Holmes C. Association between interleukin 1-beta promoter (-511) polymorphism and depressive symptoms in Alzheimer’s disease. Am J Med Genet B Neuropsychiatr Genet 2004; 124B(1):50–53PubMedCrossRefGoogle Scholar
  468. 468.
    Santos M, Kövari E, Gold G, et al. The neuroanatomical model of post-stroke depression: Towards a change of focus? J Neurol Sci 2009; 283(1–2):158–162Google Scholar
  469. 469.
    Paradiso S, Ohkubo T, Robinson RG. Vegetative and psychological symptoms associated with depressed mood over the first two years after stroke. Int J Psychiatry Med 1997; 27(2):137–157PubMedCrossRefGoogle Scholar
  470. 470.
    Iosifescu DV, Nierenberg AA, Alpert JE, et al. Comorbid medical illness and relapse of major depressive disorder in the continuation phase of treatment. Psychosomatics 2004; 45(5):419–425PubMedCrossRefGoogle Scholar
  471. 471.
    Leppävuori A, Pohjasvaara T, Vataja R, et al. Generalized anxiety disorders three to four months after ischemic stroke. Cerebrovasc Dis 2003; 16(3):257–264PubMedCrossRefGoogle Scholar
  472. 472.
    Kimura M, Tateno A, Robinson RG. Treatment of poststroke generalized anxiety disorder comorbid with poststroke depression: merged analysis of nortriptyline trials. Am J Geriatr Psychiatry 2003; 11(3):320–327PubMedGoogle Scholar
  473. 473.
    Kato M, Iwata H, Okamoto M, et al. Focal cerebral ischemia-induced escape deficit in rats is ameliorated by a reversible inhibitor of monoamine oxidase-a: implications for a novel animal model of post-stroke depression. Biol Pharm Bull 2000; 23(4):406–410PubMedCrossRefGoogle Scholar
  474. 474.
    Behan DP, Grigoriadis DE, Lovenberg T, et al. Neurobiology of corticotropin releasing factor (CRF) receptors and CRF-binding protein: implications for the treatment of CNS disorders. Mol Psychiatry 1996; 1(4):265–277PubMedGoogle Scholar
  475. 475.
    Provinciali L, Coccia M. Post-stroke and vascular depression: a critical review. Neurol Sci 2002; 22(6):417–428PubMedCrossRefGoogle Scholar
  476. 476.
    Rocco A, Afra J, Toscano M, et al. Acute subcortical stroke and early serotonergic modification: a IDAP study. Eur J Neurol 2007; 14(12):1378–1382PubMedCrossRefGoogle Scholar
  477. 477.
    Bryer JB, Starkstein SE, Votypka V, et al. Reduction of CSF monoamine metabolites in poststroke depression: a preliminary report. J Neuropsychiatry Clin Neurosci 1992; 4(4):440–442PubMedGoogle Scholar
  478. 478.
    Raab S, Plate KH. Different networks, common growth factors: shared growth factors and receptors of the vascular and the nervous system. Acta Neuropathol 2007; 113(6):607–626PubMedCrossRefGoogle Scholar
  479. 479.
    Calabrese F, Molteni R, Racagni G, et al. Neuronal plasticity: A link between stress and mood disorders. Psychoneuroendocrinology 2009; 34(Suppl 1):S208–S216Google Scholar
  480. 480.
    Musazzi L, Cattaneo A, Tardito D, et al. Early raise of BDNF in hippocampus suggests induction of posttranscriptional mechanisms by antidepressants. BMC Neurosci 2009; 10:48PubMedCrossRefGoogle Scholar
  481. 481.
    Fossati P, Radtchenko A, Boyer P. Neuroplasticity: from MRI to depressive symptoms. Eur Neuropsychopharmacol 2004; 14(Suppl 5):S503–S510PubMedCrossRefGoogle Scholar
  482. 482.
    Minami M, Kuraishi Y, Yamaguchi T, et al. Immobilization stress induces interleukin-1 beta mRNA in the rat hypothalamus. Neurosci Lett 1991; 123(2):254–256PubMedCrossRefGoogle Scholar
  483. 483.
    Spalletta G, Bossù P, Ciaramella A, et al. The etiology of poststroke depression: a review of the literature and a new hypothesis involving inflammatory cytokines. Mol Psychiatry 2006; 11(11):984–991PubMedCrossRefGoogle Scholar
  484. 484.
    Caso JR, Moro MA, Lorenzo P, et al. Involvement of IL-1beta in acute stress-induced worsening of cerebral ischaemia in rats. Eur Neuropsychopharmacol 2007; 17(9):600–607PubMedCrossRefGoogle Scholar
  485. 485.
    Loddick SA, Wong ML, Bongiorno PB, et al. Endogenous interleukin-1 receptor antagonist is neuroprotective. Biochem Biophys Res Commun 1997; 234(1):211–215PubMedCrossRefGoogle Scholar
  486. 486.
    Wong ML, Loddick SA, Bongiorno PB, et al. Focal cerebral ischemia induces CRH mRNA in rat cerebral cortex and amygdala. Neuroreport 1995; 6(13):1785–1788PubMedCrossRefGoogle Scholar
  487. 487.
    Strijbos PJ, Rothwell NJ. Interleukin-1 beta attenuates excitatory amino acid-induced neurodegeneration in vitro: involvement of nerve growth factor. J Neurosci 1995; 15(5 Pt 1):3468–3474PubMedGoogle Scholar
  488. 488.
    Benveniste EN. Cytokines: influence on glial cell gene expression and function. Chem Immunol 1992; 52:106–153PubMedCrossRefGoogle Scholar
  489. 489.
    Chao CC, Hu S, Ehrlich L, et al. Interleukin-1 and tumor necrosis factor-alpha synergistically mediate neurotoxicity: involvement of nitric oxide and of N-methyl-D-aspartate receptors. Brain Behav Immun 1995; 9(4):355–365PubMedCrossRefGoogle Scholar
  490. 490.
    Banati RB, Gehrmann J, Schubert P, et al. Cytotoxicity of microglia. Glia 1993; 7(1):111–118PubMedCrossRefGoogle Scholar
  491. 491.
    Plata-Salamán CR, ffrench-Mullen JM. Interleukin-1 beta inhibits Ca2+ channel currents in hippocampal neurons through protein kinase C. Eur J Pharmacol 1994; 266(1):1–10PubMedCrossRefGoogle Scholar
  492. 492.
    Tchelingerian JL, Vignais L, Jacque C. TNF alpha gene expression is induced in neurones after a hippocampal lesion. Neuroreport 1994; 5(5):585–588PubMedCrossRefGoogle Scholar
  493. 493.
    Barone FC, Arvin B, White RF, et al. Tumor necrosis factor-alpha. A mediator of focal ischemic brain injury. Stroke 1997; 28(6):1233–1244Google Scholar
  494. 494.
    Lavine SD, Hofman FM, Zlokovic BV. Circulating antibody against tumor necrosis factor-alpha protects rat brain from reperfusion injury. J Cereb Blood Flow Metab 1998; 18(1):52–58PubMedCrossRefGoogle Scholar
  495. 495.
    Nawashiro H, Tasaki K, Ruetzler CA, et al. TNF-alpha pretreatment induces protective effects against focal cerebral ischemia in mice. J Cereb Blood Flow Metab 1997; 17(5):483–490PubMedCrossRefGoogle Scholar
  496. 496.
    Gary DS, Bruce-Keller AJ, Kindy MS, et al. Ischemic and excitotoxic brain injury is enhanced in mice lacking the p55 tumor necrosis factor receptor. J Cereb Blood Flow Metab 1998; 18(12):1283–1287PubMedCrossRefGoogle Scholar
  497. 497.
    Barger SW, Hörster D, Furukawa K, et al. Tumor necrosis factors alpha and beta protect neurons against amyloid beta-peptide toxicity: evidence for involvement of a kappa B-binding factor and attenuation of peroxide and Ca2+ accumulation. Proc Natl Acad Sci USA 1995; 92(20):9328–9332PubMedCrossRefGoogle Scholar
  498. 498.
    Mattson MP, Barger SW, Furukawa K, et al. Cellular signaling roles of TGF beta, TNF alpha and beta APP in brain injury responses and Alzheimer’s disease. Brain Res Brain Res Rev 1997; 23(1–2):47–61PubMedCrossRefGoogle Scholar
  499. 499.
    Cheng B, Christakos S, Mattson MP. Tumor necrosis factors protect neurons against metabolic-excitotoxic insults and promote maintenance of calcium homeostasis. Neuron 1994; 12(1):139–153PubMedCrossRefGoogle Scholar
  500. 500.
    Wong GH, Kaspar RL, Vehar G. Tumor necrosis factor and lymphotoxin: protection against oxidative stress through induction of MnSOD. EXS 1996; 77:321–333PubMedGoogle Scholar
  501. 501.
    Sullivan PG, Bruce-Keller AJ, Rabchevsky AG, et al. Exacerbation of damage and altered NF-kappaB activation in mice lacking tumor necrosis factor receptors after traumatic brain injury. J Neurosci 1999; 19(15):6248–6256PubMedGoogle Scholar
  502. 502.
    Maeda Y, Matsumoto M, Hori O, et al. Hypoxia/reoxygenation-mediated induction of astrocyte interleukin 6: a paracrine mechanism potentially enhancing neuron survival. J Exp Med 1994; 180(6):2297–2308PubMedCrossRefGoogle Scholar
  503. 503.
    Loddick SA, Turnbull AV, Rothwell NJ. Cerebral interleukin-6 is neuroprotective during permanent focal cerebral ischemia in the rat. J Cereb Blood Flow Metab 1998; 18(2):176–179PubMedCrossRefGoogle Scholar
  504. 504.
    Kim JS, Yoon SS, Kim YH, et al. Serial measurement of interleukin-6, transforming growth factor-beta, and S-100 protein in patients with acute stroke. Stroke 1996; 27(9):1553–1557PubMedCrossRefGoogle Scholar
  505. 505.
    Tarkowski E, Rosengren L, Blomstrand C, et al. Early intrathecal production of interleukin-6 predicts the size of brain lesion in stroke. Stroke 1995; 26(8):1393–1398PubMedCrossRefGoogle Scholar
  506. 506.
    Craft TK, DeVries AC. Role of IL-1 in poststroke depressive-like behavior in mice. Biol Psychiatry 2006; 60(8):812–818PubMedCrossRefGoogle Scholar
  507. 507.
    Ramasubbu R, Tobias R, Bech-Hansen NT. Extended evaluation of serotonin transporter gene functional polymorphisms in subjects with post-stroke depression. Can J Psychiatry 2008; 53(3):197–201PubMedGoogle Scholar
  508. 508.
    Zhu CB, Blakely RD, Hewlett WA. The proinflammatory cytokines interleukin-1beta and tumor necrosis factor-alpha activate serotonin transporters. Neuropsychopharmacology 2006; 31(10):2121–2131PubMedGoogle Scholar
  509. 509.
    Zhang ZG, Chopp M. Neurorestorative therapies for stroke: underlying mechanisms and translation to the clinic. Lancet Neurol 2009; 8(5):491–500PubMedCrossRefGoogle Scholar
  510. 510.
    Whitney NP, Eidem TM, Peng H, et al. Inflammation mediates varying effects in neurogenesis: relevance to the pathogenesis of brain injury and neurodegenerative disorders. J Neurochem 2009; 108(6):1343–1359PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2010

Authors and Affiliations

  1. 1.Institute of NeuroscienceCarleton UniversityOttawaCanada

Personalised recommendations