Advertisement

Molecular Neurobiology

, Volume 49, Issue 1, pp 28–38 | Cite as

The Role of Inflammatory and Oxidative Stress Mechanisms in the Pathogenesis of Parkinson’s Disease: Focus on Astrocytes

  • Rituraj NiranjanEmail author
Article

Abstract

Neuroinflammation plays a key role in the pathogenesis of Parkinson’s disease (PD). Epidemiologic, animal, human, and therapeutic studies support the role of oxidative stress and inflammatory cascade in initiation and progression of PD. In Parkinson’s disease pathophysiology, activated glia affects neuronal injury and death through production of neurotoxic factors like glutamate, S100B, tumor necrosis factor alpha (TNF-α), prostaglandins, and reactive oxygen and nitrogen species. As disease progresses, inflammatory secretions engage neighboring cells, including astrocytes and endothelial cells, resulting in a vicious cycle of autocrine and paracrine amplification of inflammation leading to neurodegeneration. The exact mechanism of these inflammatory mediators in the disease progression is still poorly understood. In this review, we highlight and discuss the mechanisms of oxidative stress and inflammatory mediators by which they contribute to the disease progression. Particularly, we focus on the altered role of astroglial cells that presumably initiate and execute dopaminergic neurodegeneration in PD. In conclusion, we focus on the molecular mechanism of neurodegeneration, which contributes to the basic understanding of the role of neuroinflammation in PD pathophysiology.

Keywords

Parkinson’s disease Inflammatory mediators Oxidative stress 

Abbreviations

NGF

Nerve growth factor

GDNF

Glial cell line-derived neurotrophic factor

MANF

Mesencephalic astrocyte-derived neurotrophic factor

bFGF

Basic fibroblast growth factor

PD

Parkinson’s disease

ROS

Reactive oxygen species

RNS

Reactive nitrogen species

TNF-α

Tumor necrosis factor-α

NF-κB

Nuclear factor kappa-B

COX-2

Cyclooxygenase-2

GFAP

Glial fibrillary acidic protein

CHOP

C/EBP homologous protein 10

iNOS

Inducible nitric oxide synthase

IL-1α

Interleukin-1α

IL-1β

Interleukin-1β

IL-6

Interleukin-6

P-p38 MAPK

Phosphorylated p38 mitogen-activated protein kinase

NO

Nitrite

Notes

Acknowledgments

Lab space and facilities provided by Dr. Anil Mishra at the School of Medicine, Division of Gastroenterology and Liver Disease, Case Western Reserve University, Cleveland, OH, USA, is gratefully acknowledged.

Conflict of interest

None.

References

  1. 1.
    Minagar A, Shapshak P, Fujimura R, Ownby R, Heyes M, Eisdorfer C (2002) The role of macrophage/microglia and astrocytes in the pathogenesis of three neurologic disorders: HIV-associated dementia, Alzheimer disease, and multiple sclerosis. J Neurol Sci 202:13–23CrossRefPubMedGoogle Scholar
  2. 2.
    Balasingam V, Tejada-Berges T, Wright E, Bouckova R, Yong VW (1994) Reactive astrogliosis in the neonatal mouse brain and its modulation by cytokines. J Neurosci 14:846–856PubMedGoogle Scholar
  3. 3.
    Hu X, Zhang D, Pang H, Caudle WM, Li Y, Gao H, Liu Y, Qian L, Wilson B, Di Monte DA, Ali SF, Zhang J, Block ML, Hong JS (2008) Macrophage antigen complex-1 mediates reactive microgliosis and progressive dopaminergic neurodegeneration in the MPTP model of Parkinson’s disease. J Immunol 181:7194–7204PubMedCentralPubMedGoogle Scholar
  4. 4.
    Asanuma M, Miyazaki I (2008) Nonsteroidal anti-inflammatory drugs in experimental parkinsonian models and Parkinson’s disease. Curr Pharm Des 14:1428–1434CrossRefPubMedGoogle Scholar
  5. 5.
    Esposito G, Scuderi C, Savani C, Steardo L Jr, De Filippis D, Cottone P, Iuvone T, Cuomo V, Steardo L (2007) Cannabidiol in vivo blunts beta-amyloid induced neuroinflammation by suppressing IL-1beta and iNOS expression. Br J Pharmacol 151:1272–1279CrossRefPubMedGoogle Scholar
  6. 6.
    Wight RD, Tull CA, Deel MW, Stroope BL, Eubanks AG, Chavis JA, Drew PD, Hensley LL Resveratrol effects on astrocyte function: relevance to neurodegenerative diseases. Biochemical and biophysical research communications 426:112-115Google Scholar
  7. 7.
    Maccioni RB, Rojo LE, Fernandez JA, Kuljis RO (2009) The role of neuroimmunomodulation in Alzheimer’s disease. Ann N Y Acad Sci 1153:240–246CrossRefPubMedGoogle Scholar
  8. 8.
    Sekiyama K, Sugama S, Fujita M, Sekigawa A, Takamatsu Y, Waragai M, Takenouchi T, Hashimoto M (2012) Neuroinflammation in Parkinson's disease and related disorders: a lesson from genetically manipulated mouse models of alpha-synucleinopathies. Parkinson's Dis 2012:271732Google Scholar
  9. 9.
    Tansey MG, Goldberg MS (2009) Neuroinflammation in Parkinson’s disease: its role in neuronal death and implications for therapeutic intervention. Neurobiol DisGoogle Scholar
  10. 10.
    Albrecht S, Buerger E (2009) Potential neuroprotection mechanisms in PD: focus on dopamine agonist pramipexole. Curr Med Res Opin 25:2977–2987CrossRefPubMedGoogle Scholar
  11. 11.
    Klegeris A, McGeer PL (2000) R-(−)-Deprenyl inhibits monocytic THP-1 cell neurotoxicity independently of monoamine oxidase inhibition. Exp Neurol 166:458–464CrossRefPubMedGoogle Scholar
  12. 12.
    Guillot TS, Richardson JR, Wang MZ, Li YJ, Taylor TN, Ciliax BJ, Zachrisson O, Mercer A, Miller GW (2008) PACAP38 increases vesicular monoamine transporter 2 (VMAT2) expression and attenuates methamphetamine toxicity. Neuropeptides 42:423–434CrossRefPubMedCentralPubMedGoogle Scholar
  13. 13.
    Mena MA, Garcia de Yebenes J (2008) Glial cells as players in parkinsonism: the “good”, the “bad”, and the “mysterious” glia. Neuroscientist Rev J Bringing Neurobiol Neurol Psychiatry 14:544–560Google Scholar
  14. 14.
    Niranjan R, Kamat PK, Nath C, Shukla R (2010) Evaluation of guggulipid and nimesulide on production of inflammatory mediators and GFAP expression in LPS stimulated rat astrocytoma, cell line (C6). J Ethnopharmacol 127:625–630CrossRefPubMedGoogle Scholar
  15. 15.
    Solano RM, Casarejos MJ, Menendez-Cuervo J, Rodriguez-Navarro JA, Garcia de Yebenes J, Mena MA (2008) Glial dysfunction in parkin null mice: effects of aging. J Neurosci 28:598–611CrossRefPubMedGoogle Scholar
  16. 16.
    Tambuyzer BR, Ponsaerts P, Nouwen EJ (2009) Microglia: gatekeepers of central nervous system immunology. J Leukoc Biol 85:352–370CrossRefPubMedGoogle Scholar
  17. 17.
    Niranjan R, Nath C, Shukla R (2011) Guggulipid and nimesulide differentially regulated inflammatory genes mRNA expressions via inhibition of NF-κB and CHOP activation in LPS-stimulated rat astrocytoma cells, C6. Cell Mol Neurobiol 31:755–764CrossRefPubMedGoogle Scholar
  18. 18.
    Rogers J, Mastroeni D, Leonard B, Joyce J, Grover A (2007) Neuroinflammation in Alzheimer’s disease and Parkinson’s disease: are microglia pathogenic in either disorder? Int Rev Neurobiol 82:235–246CrossRefPubMedGoogle Scholar
  19. 19.
    Brodacki B, Staszewski J, Toczylowska B, Kozlowska E, Drela N, Chalimoniuk M, Stepien A (2008) Serum interleukin (IL-2, IL-10, IL-6, IL-4), TNFalpha, and INFgamma concentrations are elevated in patients with atypical and idiopathic parkinsonism. Neurosci Lett 441:158–162CrossRefPubMedGoogle Scholar
  20. 20.
    Dheen ST, Kaur C, Ling EA (2007) Microglial activation and its implications in the brain diseases. Curr Med Chem 14:1189–1197CrossRefPubMedGoogle Scholar
  21. 21.
    Khandhar SM, Marks WJ (2007) Epidemiology of Parkinson’s disease. Dis Mon 53:200–205CrossRefPubMedGoogle Scholar
  22. 22.
    Ton TG, Heckbert SR, Longstreth WT Jr, Rossing MA, Kukull WA, Franklin GM, Swanson PD, Smith-Weller T, Checkoway H (2006) Nonsteroidal anti-inflammatory drugs and risk of Parkinson’s disease. Mov Disord Off J Mov Disord Soc 21:964–969CrossRefGoogle Scholar
  23. 23.
    Etminan M, Carleton BC, Samii A (2008) Non-steroidal anti-inflammatory drug use and the risk of Parkinson disease: a retrospective cohort study. J Clin Neurosci 15:576–577CrossRefPubMedGoogle Scholar
  24. 24.
    van Staa TP, Smeeth L, Persson I, Parkinson J, Leufkens HG (2008) What is the harm-benefit ratio of Cox-2 inhibitors? Int J Epidemiol 37:405–413CrossRefPubMedGoogle Scholar
  25. 25.
    Hirsch EC, Hunot S, Damier P, Faucheux B (1998) Glial cells and inflammation in Parkinson’s disease: a role in neurodegeneration? Ann Neurol 44:S115–S120PubMedGoogle Scholar
  26. 26.
    Castano A, Herrera AJ, Cano J, Machado A (2002) 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 81:150–157CrossRefPubMedGoogle Scholar
  27. 27.
    Tian YY, An LJ, Jiang L, Duan YL, Chen J, Jiang B (2006) Catalpol protects dopaminergic neurons from LPS-induced neurotoxicity in mesencephalic neuron-glia cultures. Life Sci 80:193–199CrossRefPubMedGoogle Scholar
  28. 28.
    Santiago M, Hernandez-Romero MC, Machado A, Cano J (2009) Zocor Forte (simvastatin) has a neuroprotective effect against LPS striatal dopaminergic terminals injury, whereas against MPP+ does not. Eur J Pharmacol 609:58–64CrossRefPubMedGoogle Scholar
  29. 29.
    Aloe L, Fiore M (1997) TNF-alpha expressed in the brain of transgenic mice lowers central tyroxine hydroxylase immunoreactivity and alters grooming behavior. Neurosci Lett 238:65–68CrossRefPubMedGoogle Scholar
  30. 30.
    Wenk GL, McGann-Gramling K, Hauss-Wegrzyniak B, Ronchetti D, Maucci R, Rosi S, Gasparini L, Ongini E (2004) Attenuation of chronic neuroinflammation by a nitric oxide-releasing derivative of the antioxidant ferulic acid. J Neurochem 89:484–493CrossRefPubMedGoogle Scholar
  31. 31.
    Carvey PM, Chang Q, Lipton JW, Ling Z (2003) 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 8:s826–s837CrossRefPubMedGoogle Scholar
  32. 32.
    Lane EL, Soulet D, Vercammen L, Cenci MA, Brundin P (2008) Neuroinflammation in the generation of post-transplantation dyskinesia in Parkinson’s disease. Neurobiol Dis 32:220–228CrossRefPubMedGoogle Scholar
  33. 33.
    Grunblatt E, Mandel S, Youdim MB (2000) MPTP and 6-hydroxydopamine-induced neurodegeneration as models for Parkinson’s disease: neuroprotective strategies. J Neurol 247(Suppl 2):II95–II102PubMedGoogle Scholar
  34. 34.
    Meredith GE, Totterdell S, Potashkin JA, Surmeier DJ (2008) Modeling PD pathogenesis in mice: advantages of a chronic MPTP protocol. Parkinsonism Relat Disord 14(Suppl 2):S112–S115CrossRefPubMedCentralPubMedGoogle Scholar
  35. 35.
    Siddiqui A, Mallajosyula JK, Rane A, Andersen JK Ability to delay neuropathological events associated with astrocytic MAO-B increase in a parkinsonian mouse model: implications for early intervention on disease progression. Neurobiology of disease 40:444-448Google Scholar
  36. 36.
    Speciale SG (2002) MPTP: insights into parkinsonian neurodegeneration. Neurotoxicol Teratol 24:607–620CrossRefPubMedGoogle Scholar
  37. 37.
    Prasad KN, Cole WC, Kumar B (1999) Multiple antioxidants in the prevention and treatment of Parkinson’s disease. J Am Coll Nutr 18:413–423CrossRefPubMedGoogle Scholar
  38. 38.
    Bjarkam CR, Nielsen MS, Glud AN, Rosendal F, Mogensen P, Bender D, Doudet D, Moller A, Sorensen JC (2008) Neuromodulation in a minipig MPTP model of Parkinson disease. Br J Neurosurg 22(Suppl 1):S9–S12CrossRefPubMedGoogle Scholar
  39. 39.
    Wilms H, Zecca L, Rosenstiel P, Sievers J, Deuschl G, Lucius R (2007) Inflammation in Parkinson’s diseases and other neurodegenerative diseases: cause and therapeutic implications. Curr Pharm Des 13:1925–1928CrossRefPubMedGoogle Scholar
  40. 40.
    Reksidler AB, Lima MM, Zanata SM, Machado HB, da Cunha C, Andreatini R, Tufik S, Vital MA (2007) The COX-2 inhibitor parecoxib produces neuroprotective effects in MPTP-lesioned rats. Eur J Pharmacol 560:163–175CrossRefPubMedGoogle Scholar
  41. 41.
    Ros-Bernal F, Hunot S, Herrero MT, Parnadeau S, Corvol JC, Lu L, Alvarez-Fischer D, Carrillo-de Sauvage MA, Saurini F, Coussieu C, Kinugawa K, Prigent A, Hoglinger G, Hamon M, Tronche F, Hirsch EC, Vyas S Microglial glucocorticoid receptors play a pivotal role in regulating dopaminergic neurodegeneration in parkinsonism. Proc Natl Acad Sci USA 108:6632-6637Google Scholar
  42. 42.
    Pieper HC, Evert BO, Kaut O, Riederer PF, Waha A, Wullner U (2008) Different methylation of the TNF-alpha promoter in cortex and substantia nigra: Implications for selective neuronal vulnerability. Neurobiol Dis 32:521–527CrossRefPubMedGoogle Scholar
  43. 43.
    Bessler H, Djaldetti R, Salman H, Bergman M, Djaldetti M (1999) IL-1 beta, IL-2, IL-6 and TNF-alpha production by peripheral blood mononuclear cells from patients with Parkinson’s disease. Biomed Pharmacother 53:141–145CrossRefPubMedGoogle Scholar
  44. 44.
    Nagatsu T, Mogi M, Ichinose H, Togari A (2000) Changes in cytokines and neurotrophins in Parkinson’s disease. J Neural Transm Suppl:277-290Google Scholar
  45. 45.
    Bian MJ, Li LM, Yu M, Fei J, Huang F (2009) Elevated interleukin-1beta induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine aggravating dopaminergic neurodegeneration in old male mice. Brain Res 1302:256–264CrossRefPubMedGoogle Scholar
  46. 46.
    Kraft C, Reggiori F, Peter M (2009) Selective types of autophagy in yeast. Biochim Biophys Acta 1793:1404–1412CrossRefPubMedGoogle Scholar
  47. 47.
    Hofmann KW, Schuh AF, Saute J, Townsend R, Fricke D, Leke R, Souza DO, Portela LV, Chaves ML, Rieder CR (2009) Interleukin-6 serum levels in patients with Parkinson’s disease. Neurochem Res 34:1401–1404CrossRefPubMedGoogle Scholar
  48. 48.
    Allan SM, Pinteaux E (2003) The interleukin-1 system: an attractive and viable therapeutic target in neurodegenerative disease. Curr Drug Targets CNS Neurol Disord 2:293–302CrossRefPubMedGoogle Scholar
  49. 49.
    McCoy MK, Ruhn KA, Blesch A, Tansey MG TNF: a key neuroinflammatory mediator of neurotoxicity and neurodegeneration in models of Parkinson’s disease. Advances in experimental medicine and biology 691:539-540Google Scholar
  50. 50.
    Gomez-Santos C, Ferrer I, Santidrian AF, Barrachina M, Gil J, Ambrosio S (2003) Dopamine induces autophagic cell death and alpha-synuclein increase in human neuroblastoma SH-SY5Y cells. J Neurosci Res 73:341–350CrossRefPubMedGoogle Scholar
  51. 51.
    Ramirez SH, Hasko J, Skuba A, Fan S, Dykstra H, McCormick R, Reichenbach N, Krizbai I, Mahadevan A, Zhang M, Tuma R, Son YJ, Persidsky Y (2012) Activation of cannabinoid receptor 2 attenuates leukocyte-endothelial cell interactions and blood–brain barrier dysfunction under inflammatory conditions. J Neurosci Off J Soc Neurosci 32:4004–4016CrossRefGoogle Scholar
  52. 52.
    Tansey MG, Frank-Cannon TC, McCoy MK, Lee JK, Martinez TN, McAlpine FE, Ruhn KA, Tran TA (2008) Neuroinflammation in Parkinson’s disease: is there sufficient evidence for mechanism-based interventional therapy? Front Biosci 13:709–717CrossRefPubMedGoogle Scholar
  53. 53.
    Hirsch EC, Breidert T, Rousselet E, Hunot S, Hartmann A, Michel PP (2003) The role of glial reaction and inflammation in Parkinson’s disease. Ann N Y Acad Sci 991:214–228CrossRefPubMedGoogle Scholar
  54. 54.
    Sriram K, Lin GX, Jefferson AM, Roberts JR, Chapman RS, Chen BT, Soukup JM, Ghio AJ, Antonini JM Dopaminergic neurotoxicity following pulmonary exposure to manganese-containing welding fumes. Arch Toxicol 84:521-540Google Scholar
  55. 55.
    Breedveld FC (2005) Tumour necrosis factor antagonists: infliximab, adalimumab and etanercept. Ned Tijdschr Geneeskd 149:2273–2277PubMedGoogle Scholar
  56. 56.
    Cheret C, Gervais A, Lelli A, Colin C, Amar L, Ravassard P, Mallet J, Cumano A, Krause KH, Mallat M (2008) Neurotoxic activation of microglia is promoted by a nox1-dependent NADPH oxidase. J Neurosci 28:12039–12051CrossRefPubMedGoogle Scholar
  57. 57.
    Li B, Guo YS, Sun MM, Dong H, Wu SY, Wu DX, Li CY (2008) The NADPH oxidase is involved in lipopolysaccharide-mediated motor neuron injury. Brain Res 1226:199–208CrossRefPubMedGoogle Scholar
  58. 58.
    Liang X, Wang Q, Hand T, Wu L, Breyer RM, Montine TJ, Andreasson K (2005) Deletion of the prostaglandin E2 EP2 receptor reduces oxidative damage and amyloid burden in a model of Alzheimer’s disease. J Neurosci 25:10180–10187CrossRefPubMedGoogle Scholar
  59. 59.
    Sethi V, Yousry TA, Muhlert N, Ron M, Golay X, Wheeler-Kingshott C, Miller DH, Chard DT (2012) Improved detection of cortical MS lesions with phase-sensitive inversion recovery MRI. J Neurol Neurosurg Psychiatry 83:877–882CrossRefPubMedGoogle Scholar
  60. 60.
    Ward RJ, Lallemand F, de Witte P, Crichton RR, Piette J, Tipton K, Hemmings K, Pitard A, Page M, Della Corte L, Taylor D, Dexter D Anti-inflammatory actions of a taurine analogue, ethane beta-sultam, in phagocytic cells, in vivo and in vitro. Biochem Pharmacol 81:743-751Google Scholar
  61. 61.
    Svotelis A, Doyon G, Bernatchez G, Desilets A, Rivard N, Asselin C (2005) IL-1 beta-dependent regulation of C/EBP delta transcriptional activity. Biochem Biophys Res Commun 328:461–470CrossRefPubMedGoogle Scholar
  62. 62.
    Parish CL, Finkelstein DI, Tripanichkul W, Satoskar AR, Drago J, Horne MK (2002) The role of interleukin-1, interleukin-6, and glia in inducing growth of neuronal terminal arbors in mice. J Neurosci 22:8034–8041PubMedGoogle Scholar
  63. 63.
    Purohit DP, Perl DP, Haroutunian V, Powchik P, Davidson M, Davis KL (1998) Alzheimer disease and related neurodegenerative diseases in elderly patients with schizophrenia: a postmortem neuropathologic study of 100 cases. Arch Gen Psychiatry 55:205–211CrossRefPubMedGoogle Scholar
  64. 64.
    Chen LC, Smith A, Ben Y, Zukic B, Ignacio S, Moore D, Lee N (2004) Temporal gene expression patterns in G93A/SOD1 mouse. Amyotroph Lateral Scler Other Mot Neuron Disord 5:164–171CrossRefGoogle Scholar
  65. 65.
    Stefanova N, Kaufmann WA, Humpel C, Poewe W, Wenning GK (2012) Systemic proteasome inhibition triggers neurodegeneration in a transgenic mouse model expressing human alpha-synuclein under oligodendrocyte promoter: implications for multiple system atrophy. Acta Neuropathol 124:51–65CrossRefPubMedCentralPubMedGoogle Scholar
  66. 66.
    Hensley K, Mhatre M, Mou S, Pye QN, Stewart C, West M, Williamson KS (2006) On the relation of oxidative stress to neuroinflammation: lessons learned from the G93A-SOD1 mouse model of amyotrophic lateral sclerosis. Antioxid Redox Signal 8:2075–2087CrossRefPubMedGoogle Scholar
  67. 67.
    Klegeris A, McGeer PL (2002) Cyclooxygenase and 5-lipoxygenase inhibitors protect against mononuclear phagocyte neurotoxicity. Neurobiol Aging 23:787–794CrossRefPubMedGoogle Scholar
  68. 68.
    Choi SH, Bosetti F (2009) Cyclooxygenase-1 null mice show reduced neuroinflammation in response to beta-amyloid. Aging (Albany NY) 1:234–244Google Scholar
  69. 69.
    Nogawa S, Zhang F, Ross ME, Iadecola C (1997) Cyclo-oxygenase-2 gene expression in neurons contributes to ischemic brain damage. J Neurosci 17:2746–2755PubMedGoogle Scholar
  70. 70.
    Consilvio C, Vincent AM, Feldman EL (2004) Neuroinflammation, COX-2, and ALS—a dual role? Exp Neurol 187:1–10CrossRefPubMedGoogle Scholar
  71. 71.
    Teismann P, Tieu K, Choi DK, Wu DC, Naini A, Hunot S, Vila M, Jackson-Lewis V, Przedborski S (2003) Cyclooxygenase-2 is instrumental in Parkinson’s disease neurodegeneration. Proc Natl Acad Sci USA 100:5473–5478CrossRefPubMedGoogle Scholar
  72. 72.
    Minghetti L (2004) Cyclooxygenase-2 (COX-2) in inflammatory and degenerative brain diseases. J Neuropathol Exp Neurol 63:901–910PubMedGoogle Scholar
  73. 73.
    Iuvone T, Esposito G, De Filippis D, Bisogno T, Petrosino S, Scuderi C, Di Marzo V, Steardo L (2007) Cannabinoid CB1 receptor stimulation affords neuroprotection in MPTP-induced neurotoxicity by attenuating S100B up-regulation in vitro. J Mol Med 85:1379–1392CrossRefPubMedGoogle Scholar
  74. 74.
    Tzeng SF, Hsiao HY, Mak OT (2005) Prostaglandins and cyclooxygenases in glial cells during brain inflammation. Curr Drug Targets Inflamm Allergy 4:335–340CrossRefPubMedGoogle Scholar
  75. 75.
    Yasuda Y, Shinagawa R, Yamada M, Mori T, Tateishi N, Fujita S (2007) Long-lasting reactive changes observed in microglia in the striatal and substantia nigral of mice after 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. Brain Res 1138:196–202CrossRefPubMedGoogle Scholar
  76. 76.
    Kim HJ, Fan X, Gabbi C, Yakimchuk K, Parini P, Warner M, Gustafsson JA (2008) Liver X receptor beta (LXRbeta): a link between beta-sitosterol and amyotrophic lateral sclerosis–Parkinson’s dementia. Proc Natl Acad Sci USA 105:2094–2099CrossRefPubMedGoogle Scholar
  77. 77.
    Sugama S, Takenouchi T, Kitani H, Fujita M, Hashimoto M (2009) Microglial activation is inhibited by corticosterone in dopaminergic neurodegeneration. J Neuroimmunol 208:104–114CrossRefPubMedGoogle Scholar
  78. 78.
    Aoki E, Yano R, Yokoyama H, Kato H, Araki T (2009) 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 86:57–64CrossRefPubMedGoogle Scholar
  79. 79.
    Gatev P, Wichmann T (2009) Interactions between cortical rhythms and spiking activity of single basal ganglia neurons in the normal and parkinsonian state. Cereb Cortex 19:1330–1344CrossRefPubMedGoogle Scholar
  80. 80.
    Graeber MB, Streit WJ Microglia: biology and pathology. Acta Neuropathol 119:89-105Google Scholar
  81. 81.
    McGeer PL, McGeer EG (2008) Glial reactions in Parkinson’s disease. Mov Disord 23:474–483CrossRefPubMedGoogle Scholar
  82. 82.
    Vroon A, Drukarch B, Bol JG, Cras P, Breve JJ, Allan SM, Relton JK, Hoogland PV, Van Dam AM (2007) Neuroinflammation in Parkinson’s patients and MPTP-treated mice is not restricted to the nigrostriatal system: microgliosis and differential expression of interleukin-1 receptors in the olfactory bulb. Exp Gerontol 42:762–771CrossRefPubMedGoogle Scholar
  83. 83.
    Schneider JS, Denaro FJ (1988) Astrocytic responses to the dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in cat and mouse brain. J Neuropathol Exp Neurol 47:452–458CrossRefPubMedGoogle Scholar
  84. 84.
    Yuan H, Zheng JC, Liu P, Zhang SF, Xu JY, Bai LM (2007) Pathogenesis of Parkinson’s disease: oxidative stress, environmental impact factors and inflammatory processes. Neurosci Bull 23:125–130CrossRefPubMedGoogle Scholar
  85. 85.
    Katunina EA, Malykhina EA, Kuznetsov NV, Avakian GN, Gusev E, Nerobkova LN, Voronina TA, Barskov IV (2006) Antioxidants in complex treatment of Parkinson’s disease. Zh Nevrol Psikhiatr Im S S Korsakova 106:22–28PubMedGoogle Scholar
  86. 86.
    Zhou C, Huang Y, Przedborski S (2008) Oxidative stress in Parkinson’s disease: a mechanism of pathogenic and therapeutic significance. Ann N Y Acad Sci 1147:93–104CrossRefPubMedCentralPubMedGoogle Scholar
  87. 87.
    Jenner P (2003) Oxidative stress in Parkinson's disease. Ann Neurol 53(Suppl 3):S26–S36, discussion S36-28CrossRefPubMedGoogle Scholar
  88. 88.
    Ahmed M, Luggen M, Herman JH, Weiss KL, Decourten-Myers G, Quinlan JG, Khanna D (2006) Hypertrophic pachymeningitis in rheumatoid arthritis after adalimumab administration. J Rheumatol 33:2344–2346PubMedGoogle Scholar
  89. 89.
    Favier A (2006) Oxidative stress in human diseases. Ann Pharm Fr 64:390–396CrossRefPubMedGoogle Scholar
  90. 90.
    Lee WS, Tsai WJ, Yeh PH, Wei BL, Chiou WF (2006) Divergent role of calcium on Abeta- and MPTP-induced cell death in SK-N-SH neuroblastoma. Life Sci 78:1268–1275CrossRefPubMedGoogle Scholar
  91. 91.
    Ortiz-Ortiz MA, Moran JM, Bravosanpedro JM, Gonzalez-Polo RA, Niso-Santano M, Anantharam V, Kanthasamy AG, Soler G, Fuentes JM (2009) Curcumin enhances paraquat-induced apoptosis of N27 mesencephalic cells via the generation of reactive oxygen species. Neurotoxicology 30:1008–1018CrossRefPubMedCentralPubMedGoogle Scholar
  92. 92.
    Fukae J, Mizuno Y, Hattori N (2007) Mitochondrial dysfunction in Parkinson’s disease. Mitochondrion 7:58–62CrossRefPubMedGoogle Scholar
  93. 93.
    Beal MF (2003) Mitochondria, oxidative damage, and inflammation in Parkinson’s disease. Ann N Y Acad Sci 991:120–131CrossRefPubMedGoogle Scholar
  94. 94.
    Jung BD, Shin EJ, Nguyen XK, Jin CH, Bach JH, Park SJ, Nah SY, Wie MB, Bing G, Kim HC Potentiation of methamphetamine neurotoxicity by intrastriatal lipopolysaccharide administration. Neurochem Int 56:229-244Google Scholar
  95. 95.
    Akundi RS, Huang Z, Eason J, Pandya JD, Zhi L, Cass WA, Sullivan PG, Bueler H Increased mitochondrial calcium sensitivity and abnormal expression of innate immunity genes precede dopaminergic defects in Pink1-deficient mice. PloS one 6:e16038Google Scholar
  96. 96.
    Hunter RL, Dragicevic N, Seifert K, Choi DY, Liu M, Kim HC, Cass WA, Sullivan PG, Bing G (2007) Inflammation induces mitochondrial dysfunction and dopaminergic neurodegeneration in the nigrostriatal system. J Neurochem 100:1375–1386CrossRefPubMedGoogle Scholar
  97. 97.
    Lee M, Kwon BM, Suk K, McGeer E, McGeer PL Effects of obovatol on GSH depleted glia-mediated neurotoxicity and oxidative damage. Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology 7:173-186Google Scholar
  98. 98.
    Drouin-Ouellet J, Gibrat C, Bousquet M, Calon F, Kriz J, Cicchetti F The role of the MYD88-dependent pathway in MPTP-induced brain dopaminergic degeneration. Journal of neuroinflammation 8:137Google Scholar
  99. 99.
    Niranjan R, Nath C, Shukla R The mechanism of action of MPTP-induced neuroinflammation and its modulation by melatonin in rat astrocytoma cells, C6. Free radical research 44:1304-1316Google Scholar
  100. 100.
    Rappold PM, Tieu K (2010) Astrocytes and therapeutics for Parkinson’s disease. Neurother J Am Soc Exp Neuro Ther 7:413–423Google Scholar
  101. 101.
    Hauser DN, Cookson MR (2011) Astrocytes in Parkinson’s disease and DJ-1. J Neurochem 117:357–358CrossRefPubMedCentralPubMedGoogle Scholar
  102. 102.
    Niranjan R, Rajasekar N, Nath C, Shukla R (2012) The effect of guggulipid and nimesulide on MPTP-induced mediators of neuroinflammation in rat astrocytoma cells, C6. Chemico-biological interactionsGoogle Scholar
  103. 103.
    Rocha SM, Cristovao AC, Campos FL, Fonseca CP, Baltazar G (2012) Astrocyte-derived GDNF is a potent inhibitor of microglial activation. Neurobiol Dis 47:407–415CrossRefPubMedGoogle Scholar
  104. 104.
    Niranjan R, Nath C, Shukla R (2012) Melatonin attenuated mediators of neuroinflammation and alpha-7 nicotinic acetylcholine receptor mRNA expression in lipopolysaccharide (LPS) stimulated rat astrocytoma cells, C6. Free Radic Res 46:1167–1177CrossRefPubMedGoogle Scholar
  105. 105.
    Niranjan R, Nath C, Shukla R (2010) The mechanism of action of MPTP-induced neuroinflammation and its modulation by melatonin in rat astrocytoma cells, C6. Free Radic Res 44:1304–1316CrossRefPubMedGoogle Scholar
  106. 106.
    Zamanian JL, Xu L, Foo LC, Nouri N, Zhou L, Giffard RG, Barres BA (2012) Genomic analysis of reactive astrogliosis. J Neurosci Off J Soc Neurosci 32:6391–6410CrossRefGoogle Scholar
  107. 107.
    Karpuk N, Burkovetskaya M, Kielian T (2012) Neuroinflammation alters voltage-dependent conductance in striatal astrocytes. J Neurophysiol 108:112–123CrossRefPubMedGoogle Scholar
  108. 108.
    Tarassishin L, Loudig O, Bauman A, Shafit-Zagardo B, Suh HS, Lee SC (2011) Interferon regulatory factor 3 inhibits astrocyte inflammatory gene expression through suppression of the proinflammatory miR-155 and miR-155*. Glia 59:1911–1922CrossRefPubMedCentralPubMedGoogle Scholar
  109. 109.
    Madeira JM, Beloukhina N, Boudreau K, Boettcher TA, Gurley L, Walker DG, McNeil WS, Klegeris A (2012) Cobalt(II) beta-ketoaminato complexes as novel inhibitors of neuroinflammation. Eur J Pharmacol 676:81–88CrossRefPubMedGoogle Scholar
  110. 110.
    Waak J, Weber SS, Waldenmaier A, Gorner K, Alunni-Fabbroni M, Schell H, Vogt-Weisenhorn D, Pham TT, Reumers V, Baekelandt V, Wurst W, Kahle PJ (2009) Regulation of astrocyte inflammatory responses by the Parkinson’s disease-associated gene DJ-1. FASEB J Off Publ Fed Am Soc Exp Biol 23:2478–2489Google Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  1. 1.Division of Gastroenterology and Liver DiseasesCase Western Reserve University, School of MedicineClevelandUSA

Personalised recommendations