Current Neurology and Neuroscience Reports

, Volume 12, Issue 4, pp 350–358 | Cite as

Neuroinflammation and Non-motor Symptoms: The Dark Passenger of Parkinson’s Disease?

Movement Disorders (SA Factor, Section Editor)


Generally speaking, inflammation as a key piece to the Parkinson’s disease (PD) puzzle is a relatively new concept. Acceptance of this concept has gained ground as studies by various researchers have demonstrated the potential of mitigating nigral cell death by curtailing inflammation in animal models of PD. We propose that the significance of inflammation in PD pathology may extend beyond the nigrostriatal region. In the current review, we present an argument for this based on the Braak staging and discuss how inflammation might contribute to the development of non-motor PD symptoms.


Parkinson’s disease Braak staging Inflammation Interleukin-1/-6 Tumor necrosis factor-α Non-motor symptoms Depression Cognitive deficits Gastrointestinal tract Sleep Psychosis LRRK2 Parkin Lewy body Substantia nigra HLA-DRA Helicobacter pylori Lipopolysaccharide Alzheimer’s disease Arthritis Microglia H5N1 Crohn’s disease Cytokines 


Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    Braak H, Del Tredici K. Invited article: nervous system pathology in sporadic Parkinson disease. Neurology. 2008;70(20):1916–25.PubMedCrossRefGoogle Scholar
  2. 2.
    Braak H, Ghebremedhin E, Rüb U, et al. Stages in the development of Parkinson’s disease-related pathology. Cell Tissue Res. 2004;318(1):121–34.PubMedCrossRefGoogle Scholar
  3. 3.
    Hawkes CH, Del Tredici K, Braak H. Parkinson’s disease: a dual-hit hypothesis. Neuropathol Appl Neurobiol. 2007;33(6):599–614.PubMedCrossRefGoogle Scholar
  4. 4.
    Hawkes CH, Del Tredici K, Braak H. A timeline for Parkinson’s disease. Parkinsonism Relat Disord. 2010;16(2):79–84.PubMedCrossRefGoogle Scholar
  5. 5.
    • Jang H, Boltz D, Sturm-Ramirez K, et al. Highly pathogenic H5N1 influenza virus can enter the central nervous system and induce neuroinflammation and neurodegeneration. Proc Natl Acad Sci U S A. 2009;106(33):14063–8. This study shows direct evidence for Braak staging and that highly pathogenic H5N1 can recapitulate many PD features.PubMedCrossRefGoogle Scholar
  6. 6.
    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. 2007;208(1):1–25.PubMedCrossRefGoogle Scholar
  7. 7.
    Whitton PS. Inflammation as a causative factor in the aetiology of Parkinson’s disease. Br J Pharmacol. 2007;150(8):963–76.PubMedCrossRefGoogle Scholar
  8. 8.
    McCoy MK, Tansey MG. TNF signaling inhibition in the CNS: implications for normal brain function and neurodegenerative disease. J Neuroinflammation. 2008;5:45.PubMedCrossRefGoogle Scholar
  9. 9.
    McGeer PL, McGeer EG. Glial reactions in Parkinson’s disease. Mov Disord. 2008;23(4):474–83.PubMedCrossRefGoogle Scholar
  10. 10.
    Hirsch EC, Hunot S. Neuroinflammation in Parkinson’s disease: a target for neuroprotection? Lancet Neurol. 2009;8(4):382–97.PubMedCrossRefGoogle Scholar
  11. 11.
    Barnum CJ, Tansey MG. Modeling neuroinflammatory pathogenesis of Parkinson’s disease. Prog Brain Res. 2010;184:113–132.12.PubMedCrossRefGoogle Scholar
  12. 12.
    Glass CK, Saijo K, Winner B, Marchetto MC, Gage FH. Mechanisms underlying inflammation in neurodegeneration. Cell. 2010;140(6):918–34.PubMedCrossRefGoogle Scholar
  13. 13.
    Tansey MG, Goldberg MS. Neuroinflammation in Parkinson’s disease: its role in neuronal death and implications for therapeutic intervention. Neurobiol Dis. 2010;37(3):510–8.PubMedCrossRefGoogle Scholar
  14. 14.
    •• Hamza TH, Zabetian CP, Tenesa A, et al. Common genetic variation in the HLA region is associated with late-onset sporadic Parkinson’s disease. Nat Genet. 2010;42(9):781–5. Provides additional evidence that genes associated with PD have inflammatory consequences.PubMedCrossRefGoogle Scholar
  15. 15.
    Boss JM, Jensen PE. Transcriptional regulation of the MHC class II antigen presentation pathway. Curr Opin Immunol. 2003;15(1):105–11.PubMedCrossRefGoogle Scholar
  16. 16.
    Do CB, Tung JY, Dorfman E, et al. Web-based genome-wide association study identifies two novel loci and a substantial genetic component for Parkinson’s disease. PLoS Genet. 2011;7(6):e1002141.PubMedCrossRefGoogle Scholar
  17. 17.
    Guo Y, Deng X, Zheng W, et al. HLA rs3129882 variant in chinese han patients with late-onset sporadic Parkinson disease. Neurosci Lett. 2011;501(3):185–7.PubMedCrossRefGoogle Scholar
  18. 18.
    Hill-Burns EM, Factor SA, Zabetian CP, et al. Evidence for more than one Parkinson’s disease-associated variant within the HLA region. PLoS One. 2011;6(11):e27109.PubMedCrossRefGoogle Scholar
  19. 19.
    Nalls MA, Plagnol V, Hernandez DG, et al. Imputation of sequence variants for identification of genetic risks for Parkinson’s disease: a meta-analysis of genome-wide association studies. Lancet. 2011;377(9766):641–9.PubMedCrossRefGoogle Scholar
  20. 20.
    Puschmann A, Verbeeck C, Heckman MG, et al. Human leukocyte antigen variation and Parkinson’s disease. Parkinsonism Relat Disord. 2011;17(5):376–8.PubMedCrossRefGoogle Scholar
  21. 21.
    Simon-Sanchez J, van Hilten JJ, van de Warrenburg B, et al. Genome-wide association study confirms extant PD risk loci among the Dutch. Eur J Hum Genet. 2011;19(6):655–61.PubMedCrossRefGoogle Scholar
  22. 22.
    Chiang HL, Lee-Chen GJ, Chen CM, et al. Genetic analysis of HLA-DRA region variation in Taiwanese Parkinson’s disease. Parkinsonism Relat Disord 2012.Google Scholar
  23. 23.
    Kruger R, Hardt C, Tschentscher F, et al. Genetic analysis of immunomodulating factors in sporadic Parkinson’s disease. J Neural Transm. 2000;107(5):553–62.PubMedCrossRefGoogle Scholar
  24. 24.
    Nishimura M, Mizuta I, Mizuta E, et al. Tumor necrosis factor gene polymorphisms in patients with sporadic Parkinson’s disease. Neurosci Lett. 2001;311(1):1–4.PubMedCrossRefGoogle Scholar
  25. 25.
    Wu YR, Feng IH, Lyu RK, et al. Tumor necrosis factor-alpha promoter polymorphism is associated with the risk of Parkinson’s disease. Am J Med Genet B Neuropsychiatr Genet. 2007;144B(3):300–4.PubMedCrossRefGoogle Scholar
  26. 26.
    Wahner AD, Sinsheimer JS, Bronstein JM, et al. Inflammatory cytokine gene polymorphisms and increased risk of Parkinson disease. Arch Neurol. 2007;64(6):836–40.PubMedCrossRefGoogle Scholar
  27. 27.
    Bialecka M, Klodowska-Duda G, Kurzawski M, et al. Interleukin-10 (IL10) and tumor necrosis factor alpha (TNF) gene polymorphisms in Parkinson’s disease patients. Parkinsonism Relat Disord. 2008;14(8):636–40.PubMedCrossRefGoogle Scholar
  28. 28.
    Wu YR, Chen CM, Hwang JC, et al. Interleukin-1 alpha polymorphism has influence on late-onset sporadic Parkinson’s disease in Taiwan. J Neural Transm. 2007;114(9):1173–7.PubMedCrossRefGoogle Scholar
  29. 29.
    Frank-Cannon TC, Alto LT, McAlpine FE, et al. Does neuroinflammation fan the flame in neurodegenerative diseases? Mol Neurodegener. 2009;4:47.PubMedCrossRefGoogle Scholar
  30. 30.
    Corti O, Lesage S, Brice A. What genetics tells us about the causes and mechanisms of Parkinson’s disease. Physiol Rev. 2011;91(4):1161–218.PubMedCrossRefGoogle Scholar
  31. 31.
    Shimura H, Hattori N, Kubo S, et al. Familial Parkinson disease gene product, parkin, is a ubiquitin-protein ligase. Nat Genet. 2000;25(3):302–5.PubMedCrossRefGoogle Scholar
  32. 32.
    Narendra D, Tanaka A, Suen DF, et al. Parkin is recruited selectively to impaired mitochondria and promotes their autophagy. J Cell Biol. 2008;183(5):795–803.PubMedCrossRefGoogle Scholar
  33. 33.
    Goldberg MS, Fleming SM, Palacino JJ, et al. Parkin-deficient mice exhibit nigrostriatal deficits but not loss of dopaminergic neurons. J Biol Chem. 2003;278(44):43628–35.PubMedCrossRefGoogle Scholar
  34. 34.
    Zhu XR, Maskri L, Herold C, et al. Non-motor behavioural impairments in parkin-deficient mice. Eur J Neurosci. 2007;26(7):1902–11.PubMedCrossRefGoogle Scholar
  35. 35.
    Frank-Cannon TC, Tran T, Ruhn KA, et al. Parkin deficiency increases vulnerabiity to inflammation-related nigral degeneration. J Neurosci. 2008;28(43):10825–34.PubMedCrossRefGoogle Scholar
  36. 36.
    Tran TA, Nguyen AD, Chang J, et al. Lipopolysaccharide and tumor necrosis factor regulate Parkin expression via nuclear factor-kappa B. PLoS One. 2011;6(8):e23660.PubMedCrossRefGoogle Scholar
  37. 37.
    Hakimi M, Selvanantham T, Swinton E, et al. Parkinson’s disease-linked LRRK2 is expressed in circulating and tissue immune cells and upregulated following recognition of microbial structures. J Neural Transm. 2011;118(5):795–808.PubMedCrossRefGoogle Scholar
  38. 38.
    •• Liu Z, Lee J, Krummey S, et al. The kinase LRRK2 is a regulator of the transcription factor NFAT that modulates the severity of inflammatory bowel disease. Nat Immunol. 2011;12(11):1063–70. Provides additional evidence that genes associated with PD have inflammatory consequences.PubMedCrossRefGoogle Scholar
  39. 39.
    Monticelli S, Rao A. NFAT1 and NFAT2 are positive regulators of IL-4 gene transcription. Eur J Immunol. 2002;32(10):2971–8.PubMedCrossRefGoogle Scholar
  40. 40.
    Menza M, Dobkin RD, Marin H, et al. The role of inflammatory cytokines in cognition and other non-motor symptoms of Parkinson’s disease. Psychosomatics. 2010;51(6):474–9.PubMedGoogle Scholar
  41. 41.
    Blaser MJ. Who are we? Indigenous microbes and the ecology of human diseases. EMBO Rep. 2006;7(10):956–60.PubMedCrossRefGoogle Scholar
  42. 42.
    Nielsen HH, Qiu J, Friis S, et al. Treatment for Helicobacter pylori infection and risk of parkinson’s disease in Denmark. Eur J Neurol 2012.Google Scholar
  43. 43.
    Bjarnason IT, Charlett A, Dobbs RJ, et al. Role of chronic infection and inflammation in the gastrointestinal tract in the etiology and pathogenesis of idiopathic parkinsonism. Part 2: response of facets of clinical idiopathic parkinsonism to helicobacter pylori eradication. A randomized, double-blind, placebo-controlled efficacy study. Helicobacter. 2005;10(4):276–87.PubMedCrossRefGoogle Scholar
  44. 44.
    Dobbs RJ, Dobbs SM, Weller C, et al. Helicobacter hypothesis for idiopathic parkinsonism: before and beyond. Helicobacter. 2008;13(5):309–22.PubMedCrossRefGoogle Scholar
  45. 45.
    Forsyth CB, Shannon KM, Kordower JH, et al. Increased intestinal permeability correlates with sigmoid mucosa alpha-synuclein staining and endotoxin exposure markers in early Parkinson’s disease. PLoS One. 2011;6(12):e28032.PubMedCrossRefGoogle Scholar
  46. 46.
    Savica R, Carlin JM, Grossardt BR, et al. Medical records documentation of constipation preceding Parkinson disease: a case–control study. Neurology. 2009;73(21):1752–8.PubMedCrossRefGoogle Scholar
  47. 47.
    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):414–8.PubMedCrossRefGoogle Scholar
  48. 48.
    Ishihara-Paul L, Wainwright NW, Khaw KT, et al. Prospective association between emotional health and clinical evidence of Parkinson’s disease. Eur J Neurol. 2008;15(11):1148–54.PubMedCrossRefGoogle Scholar
  49. 49.
    Blonder LX, Slevin JT. Emotional dysfunction in Parkinson’s disease. Behav Neurol. 2011;24(3):201–17.PubMedGoogle Scholar
  50. 50.
    Aarsland D, Påhlhagen S, Ballard CG, et al. Depression in Parkinson disease–epidemiology, mechanisms and management. Nat Rev Neurol. 2012;8(1):35–47.CrossRefGoogle Scholar
  51. 51.
    Hinnell C, Hurt CS, Landau S, et al. Nonmotor versus motor symptoms: how much do they matter to health status in Parkinson’s disease? Mov Disord. 2012;27(2):236–41.PubMedCrossRefGoogle Scholar
  52. 52.
    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):961–6.PubMedCrossRefGoogle Scholar
  53. 53.
    Raedler TJ. Inflammatory mechanisms in major depressive disorder. Curr Opin Psychiatry. 2011;24(6):519–25.PubMedGoogle Scholar
  54. 54.
    Raison CL, Miller AH. Is depression an inflammatory disorder? Curr Psychiatry Rep. 2011;13(6):467–75.PubMedCrossRefGoogle Scholar
  55. 55.
    Harms A, Barnum CJ, Ruhn KA, et al. Delayed dominant-negative TNF gene therapy halts progressive loss of nigral dopaminergic neurons in a rat model of Parkinson’s disease. Mol Ther. 2010;19(1):46–52.PubMedCrossRefGoogle Scholar
  56. 56.
    McCoy MK, Martinez TN, Ruhn KA, et al. Blocking soluble tumor necrosis factor signaling with dominant-negative tumor necrosis factor inhibitor attenuates loss of dopaminergic neurons in models of Parkinson’s disease. J Neurosci. 2006;26(37):9365–75.PubMedCrossRefGoogle Scholar
  57. 57.
    McCoy MK, Ruhn KA, Martinez TN, et al. Intranigral lentiviral delivery of dominant-negative TNF attenuates neurodegeneration and behavioral deficits in hemiparkinsonian rats. Mol Ther. 2008;16(9):1572–9.PubMedCrossRefGoogle Scholar
  58. 58.
    Harms AS, Lee JK, Nguyen TA, et al. Regulation of microglia effector functions by tumor necrosis factor signaling. Glia. 2012;60(2):189–202.PubMedCrossRefGoogle Scholar
  59. 59.
    Dowlati Y, Herrmann N, Swardfager W, et al. A meta-analysis of cytokines in major depression. Biol Psychiatry. 2010;67(5):446–57.PubMedCrossRefGoogle Scholar
  60. 60.
    Pålhagen S, Qi H, Mårtensson B, et al. Monoamines, BDNF, IL-6 and corticosterone in CSF in patients with Parkinson’s disease and major depression. J Neurol. 2010;257(4):524–32.PubMedCrossRefGoogle Scholar
  61. 61.
    Haroon E, Raison CL, Miller AH. Psychoneuroimmunology meets neuropsychopharmacology: translational implications of the impact of inflammation on behavior. neuropsychopharmacology: official publication of the American College of Neuropsychopharmacology 2011.Google Scholar
  62. 62.
    Chung YC, Kim SR, Park JY, et al. Fluoxetine prevents MPTP-induced loss of dopaminergic neurons by inhibiting microglial activation. Neuropharmacology. 2011;60(6):963–74.PubMedCrossRefGoogle Scholar
  63. 63.
    Chung YC, Kim SR, Jin BK. Paroxetine prevents loss of nigrostriatal dopaminergic neurons by inhibiting brain inflammation and oxidative stress in an experimental model of Parkinson’s disease. J Immunol. 2010;185(2):1230–7.PubMedCrossRefGoogle Scholar
  64. 64.
    Chung ES, Chung YC, Bok E, et al. Fluoxetine prevents LPS-induced degeneration of nigral dopaminergic neurons by inhibiting microglia-mediated oxidative stress. Brain Res. 2010;1363:143–50.PubMedCrossRefGoogle Scholar
  65. 65.
    Vgontzas AN, Bixler EO, Lin HM, et al. IL-6 and its circadian secretion in humans. Neuroimmunomodulation. 2005;12(3):131–40.PubMedCrossRefGoogle Scholar
  66. 66.
    Vgontzas AN, Papanicolaou DA, Bixler EO, et al. Circadian interleukin-6 secretion and quantity and depth of sleep. J Clin Endocrinol Metab. 1999;84(8):2603–7.PubMedCrossRefGoogle Scholar
  67. 67.
    Irwin M, McClintick J, Costlow C, et al. Partial night sleep deprivation reduces natural killer and cellular immune responses in humans. FASEB J. 1996;10(5):643–53.PubMedGoogle Scholar
  68. 68.
    Shearer WT, Reuben JM, Mullington JM, et al. Soluble TNF-alpha receptor 1 and IL-6 plasma levels in humans subjected to the sleep deprivation model of spaceflight. J Allergy Clin Immunol. 2001;107(1):165–70.PubMedCrossRefGoogle Scholar
  69. 69.
    van Leeuwen WM, Lehto M, Karisola P, et al. Sleep restriction increases the risk of developing cardiovascular diseases by augmenting proinflammatory responses through IL-17 and CRP. PLoS One. 2009;4(2):e4589.PubMedCrossRefGoogle Scholar
  70. 70.
    Chennaoui M, Sauvet F, Drogou C, et al. Effect of one night of sleep loss on changes in tumor necrosis factor alpha (TNF-alpha) levels in healthy men. Cytokine. 2011;56(2):318–24.PubMedCrossRefGoogle Scholar
  71. 71.
    Vgontzas AN, Papanicolaou DA, Bixler EO, et al. Elevation of plasma cytokines in disorders of excessive daytime sleepiness: role of sleep disturbance and obesity. J Clin Endocrinol Metab. 1997;82(5):1313–6.PubMedCrossRefGoogle Scholar
  72. 72.
    Vgontzas AN, Zoumakis M, Papanicolaou DA, et al. Chronic insomnia is associated with a shift of interleukin-6 and tumor necrosis factor secretion from nighttime to daytime. Metabolism. 2002;51(7):887–92.PubMedCrossRefGoogle Scholar
  73. 73.
    Bower JE, Ganz PA, Irwin MR, et al. Inflammation and behavioral symptoms after breast cancer treatment: do fatigue, depression, and sleep disturbance share a common underlying mechanism? J Clin Oncol. 2011;29(26):3517–22.PubMedCrossRefGoogle Scholar
  74. 74.
    Kim HJ, Barsevick AM, Fang CY, et al. Common biological pathways underlying the psychoneurological symptom cluster in cancer patients. Cancer Nurs 2012.Google Scholar
  75. 75.
    Chen R, Yin Y, Zhao Z, et al. Elevation of serum TNF-alpha levels in mild and moderate Alzheimer patients with daytime sleepiness. J Neuroimmunol, 2012.Google Scholar
  76. 76.
    Irwin MR, Carrillo C, Olmstead R. Sleep loss activates cellular markers of inflammation: sex differences. Brain Behav Immun. 2010;24(1):54–7.PubMedCrossRefGoogle Scholar
  77. 77.
    Abad VC, Sarinas PS, Guilleminault C. Sleep and rheumatologic disorders. Sleep Med Rev. 2008;12(3):211–28.PubMedCrossRefGoogle Scholar
  78. 78.
    Wells G, Li T, Tugwell P. Investigation into the impact of abatacept on sleep quality in patients with rheumatoid arthritis, and the validity of the MOS-sleep questionnaire sleep disturbance scale. Ann Rheum Dis. 2010;69(10):1768–73.PubMedCrossRefGoogle Scholar
  79. 79.
    Deodhar A, Braun J, Inman RD, et al. Golimumab reduces sleep disturbance in patients with active ankylosing spondylitis: results from a randomized, placebo-controlled trial. Arthritis Care Res (Hoboken). 2010;62(9):1266–71.CrossRefGoogle Scholar
  80. 80.
    Fragiadaki K, Tektonidou MG, Konsta M, et al. Sleep disturbances and interleukin 6 receptor inhibition in rheumatoid arthritis. J Rheumatol. 2012;39(1):60–2.PubMedCrossRefGoogle Scholar
  81. 81.
    Williamson LL, Sholar PW, Mistry RS, et al. Microglia and memory: modulation by early-life infection. J Neurosci. 2011;31(43):15511–21.PubMedCrossRefGoogle Scholar
  82. 82.
    Fidalgo AR, Cibelli M, White JP, et al. Systemic inflammation enhances surgery-induced cognitive dysfunction in mice. Neurosci Lett. 2011;498(1):63–6.PubMedCrossRefGoogle Scholar
  83. 83.
    Cibelli M, Fidalgo AR, Terrando N, et al. Role of interleukin-1beta in postoperative cognitive dysfunction. Ann Neurol. 2010;68(3):360–8.PubMedCrossRefGoogle Scholar
  84. 84.
    Terrando N, Monaco C, Ma D, et al. Tumor necrosis factor-alpha triggers a cytokine cascade yielding postoperative cognitive decline. Proc Natl Acad Sci U S A. 2010;107(47):20518–22.PubMedCrossRefGoogle Scholar
  85. 85.
    Terrando N, Eriksson LI, Ryu JK, et al. Resolving postoperative neuroinflammation and cognitive decline. Ann Neurol. 2011;70(6):986–95.PubMedCrossRefGoogle Scholar
  86. 86.
    Jefferson AL, Massaro JM, Beiser AS, et al. Inflammatory markers and neuropsychological functioning: the framingham heart study. Neuroepidemiology. 2011;37(1):21–30.PubMedCrossRefGoogle Scholar
  87. 87.
    Carmeli E, Imam B, Bachar A, Merrick J. Inflammation and oxidative stress as biomarkers of premature aging in persons with intellectual disability. Res Dev Disabil. 2012;33(2):369–75.PubMedCrossRefGoogle Scholar
  88. 88.
    Kamer AR, Morse DE, Holm-Pedersen P, et al. Periodontal inflammation in relation to cognitive function in an older adult danish population. J Alzheimers Dis. 2012;28(3):613–24.PubMedGoogle Scholar
  89. 89.
    Kitazawa M, Cheng D, Tsukamoto MR, et al. Blocking IL-1 signaling rescues cognition, attenuates tau pathology, and restores neuronal beta-catenin pathway function in an Alzheimer’s disease model. J Immunol. 2011;187(12):6539–49.PubMedCrossRefGoogle Scholar
  90. 90.
    Parachikova A, Vasilevko V, Cribbs DH, et al. Reductions in amyloid-beta-derived neuroinflammation, with minocycline, restore cognition but do not significantly affect tau hyperphosphorylation. J Alzheimers Dis. 2010;21(2):527–42.PubMedGoogle Scholar
  91. 91.
    Fenelon G, Mahieux F, huon R, Ziegler M. Hallucinations in Parkinson’s disease: prevalence, phenomenology and risk factors. Brain. 2000;123(Pt 4):733–45.PubMedCrossRefGoogle Scholar
  92. 92.
    Zahodne LB, Fernandez HH. Pathophysiology and treatment of psychosis in Parkinson’s disease: a review. Drugs Aging. 2008;25(8):665–82.PubMedCrossRefGoogle Scholar
  93. 93.
    Meyer U, Weiner I, McAlonan GM, Feldon J. The neuropathological contribution of prenatal inflammation to schizophrenia. Expert Rev Neurother. 2011;11(1):29–32.PubMedCrossRefGoogle Scholar
  94. 94.
    Mondelli V, Cattaneo A, Belvederi Murri M, et al. Stress and inflammation reduce brain-derived neurotrophic factor expression in first-episode psychosis: a pathway to smaller hippocampal volume. J Clin Psychiatry. 2011;72(12):1677–84.PubMedCrossRefGoogle Scholar
  95. 95.
    Suvisaari J, Loo BM, Saarni SE, et al. Inflammation in psychotic disorders: a population-based study. Psychiatry Res. 2011;189(2):305–11.PubMedCrossRefGoogle Scholar
  96. 96.
    Arnett HA, Mason J, Marino M, et al. TNF alpha promotes proliferation of oligodendrocyte progenitors and remyelination. Nat Neurosci. 2001;4(11):1116–22.PubMedCrossRefGoogle Scholar
  97. 97.
    Garcia I, Olleros ML, Quesniaux VF, et al. Roles of soluble and membrane TNF and related ligands in mycobacterial infections: effects of selective and non-selective TNF inhibitors during infection. Adv Exp Med Biol. 2011;691:187–201.PubMedCrossRefGoogle Scholar
  98. 98.
    Muller N. COX-2 inhibitors as antidepressants and antipsychotics: clinical evidence. Curr Opin Investig Drugs. 2010;11(1):31–42.PubMedGoogle Scholar
  99. 99.
    Szabó N, Kincses ZT, Toldi J, Vécsei L. Altered tryptophan metabolism in Parkinson’s disease: a possible novel therapeutic approach. J Neurol Sci. 2011;310(1–2):256–60.PubMedCrossRefGoogle Scholar
  100. 100.
    Barnum CJ, Eskow KL, Dupre K, et al. Exogenous corticosterone reduces L-DOPA-induced dyskinesia in the hemi-parkinsonian rat: role for interleukin-1beta. Neuroscience. 2008;156(1):30–41.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  1. 1.Department of PhysiologySchool of Medicine at Emory UniversityAtlantaUSA
  2. 2.Emory University School of MedicineAtlantaUSA

Personalised recommendations