Microglia activation-induced mesencephalic dopaminergic neurodegeneration--- an in vitro model for Parkinson’s disease
Received date: 20 May 2012
Accepted date: 27 Jun 2012
Published date: 01 Oct 2012
Copyright
Uncontrolled and chronic microglia activation has been implicated in the process of dopaminergic neuron degeneration in sporadic Parkinson’s disease (PD). Elevated proinflammatory mediators, presumably from activated microglia (e.g., cytokines, PGE2, nitric oxide, and superoxide radical), have been observed in PD patients and are accompanied by dopaminergic neuronal loss. Preclinical studies have demonstrated the deleterious effects of proinflammatory mediators in various in vivo and in vitro models of PD. The use of in vitro studies provides a unique tool to investigate the interaction between neurons and microglia and is especially valuable when considering the role of activated microglia in neuronal death. Here we summarize findings highlighting the potential mechanisms of microglia-mediated neurodegeneration in PD.
Key words： dopaminergic neurons; microglia activation; nitric oxide; cytokines; PGE2; p38 MAPK
Bin XING , Guoying BING . Microglia activation-induced mesencephalic dopaminergic neurodegeneration--- an in vitro model for Parkinson’s disease[J]. Frontiers in Biology, 2012 , 7(5) : 404 -411 . DOI: 10.1007/s11515-012-1239-6
| 1 |
Arimoto T, Bing G (2003). Up-regulation of inducible nitric oxide synthase in the substantia nigra by lipopolysaccharide causes microglial activation and neurodegeneration. Neurobiol Dis, 12(1): 35–45
|
| 2 |
Arimoto T, Choi D Y, Lu X, Liu M, Nguyen X V, Zheng N, Stewart C A, Kim H C, Bing G (2007). Interleukin-10 protects against inflammation-mediated degeneration of dopaminergic neurons in substantia nigra. Neurobiol Aging, 28(6): 894–906
|
| 3 |
Betarbet R, Sherer T B, MacKenzie G, Garcia-Osuna M, Panov A V, Greenamyre J T (2000). Chronic systemic pesticide exposure reproduces features of Parkinson’s disease. Nat Neurosci, 3(12): 1301–1306
|
| 4 |
Bing G Y, Lu N A,
|
| 5 |
Blandini F, Armentero M T (2012). Animal models of Parkinson’s disease. FEBS J, 279(7): 1156–1166
|
| 6 |
Block M L, Hong J S (2005). Microglia and inflammation-mediated neurodegeneration: multiple triggers with a common mechanism. Prog Neurobiol, 76(2): 77–98
|
| 7 |
Boka G, Anglade P, Wallach D, Javoy-Agid F, Agid Y, Hirsch E C (1994). Immunocytochemical analysis of tumor necrosis factor and its receptors in Parkinson’s disease. Neurosci Lett, 172(1–2): 151–154
|
| 8 |
Brooks A I, Chadwick C A, Gelbard H A, Cory-Slechta D A, Federoff H J (1999). Paraquat elicited neurobehavioral syndrome caused by dopaminergic neuron loss. Brain Res, 823(1–2): 1–10
|
| 9 |
Cannon J R, Tapias V, Na H M, Honick A S, Drolet R E, Greenamyre J T (2009). A highly reproducible rotenone model of Parkinson’s disease. Neurobiol Dis, 34(2): 279–290
|
| 10 |
Carrasco E, Casper D, Werner P (2007). PGE(2) receptor EP1 renders dopaminergic neurons selectively vulnerable to low-level oxidative stress and direct PGE(2) neurotoxicity. J Neurosci Res, 85(14): 3109–3117
|
| 11 |
Castaño A, Herrera A J, Cano J, Machado A (1998). Lipopolysaccharide intranigral injection induces inflammatory reaction and damage in nigrostriatal dopaminergic system. J Neurochem, 70(4): 1584–1592
|
| 12 |
Choi D Y, Liu M, Hunter R L, Cass W A, Pandya J D, Sullivan P G, Shin E J, Kim H C, Gash D M, Bing G (2009). Striatal neuroinflammation promotes Parkinsonism in rats. PLoS ONE, 4(5): e5482
|
| 13 |
Choi W S, Eom D S, Han B S, Kim W K, Han B H, Choi E J, Oh T H, Markelonis G J, Cho J W, Oh Y J (2004). Phosphorylation of p38 MAPK induced by oxidative stress is linked to activation of both caspase-8- and-9-mediated apoptotic pathways in dopaminergic neurons. J Biol Chem, 279(19): 20451–20460
|
| 14 |
Dehmer T, Lindenau J, Haid S, Dichgans J, Schulz J B (2000). Deficiency of inducible nitric oxide synthase protects against MPTP toxicity in vivo. J Neurochem, 74(5): 2213–2216
|
| 15 |
Du Y, Ma Z, Lin S, Dodel R C, Gao F, Bales K R, Triarhou L C, Chernet E, Perry K W, Nelson D L, Luecke S, Phebus L A, Bymaster F P, Paul S M (2001). Minocycline prevents nigrostriatal dopaminergic neurodegeneration in the MPTP model of Parkinson’s disease. Proc Natl Acad Sci USA, 98(25): 14669–14674
|
| 16 |
Fontaine V, Mohand-Said S (2002). Neurodegenerative and neuroprotective effects of tumor necrosis factor (TNF) in retinal ischemia: opposite roles of TNF receptor 1 and TNF receptor 2. The Journal of neuroscience, 22(7): RC216
|
| 17 |
Gao H M, Jiang J, Wilson B, Zhang W, Hong J S, Liu B (2002). Microglial activation-mediated delayed and progressive degeneration of rat nigral dopaminergic neurons: relevance to Parkinson’s disease. J Neurochem, 81(6): 1285–1297
|
| 18 |
Gao H M, Kotzbauer P T (2008). Neuroinflammation and oxidation/nitration of alpha-synuclein linked to dopaminergic neurodegeneration. The Journal of neuroscience, 28(30): 7687–7698
|
| 19 |
Gao H M, Zhou H (2011). HMGB1 acts on microglia Mac1 to mediate chronic neuroinflammation that drives progressive neurodegeneration.” J Neurosci, 31(3): 1081–1092
|
| 20 |
Gao L, Zackert W E, Hasford J J, Danekis M E, Milne G L, Remmert C, Reese J, Yin H, Tai H H, Dey S K, Porter N A, Morrow J D (2003). Formation of prostaglandins E2 and D2 via the isoprostane pathway: a mechanism for the generation of bioactive prostaglandins independent of cyclooxygenase. J Biol Chem, 278(31): 28479–28489
|
| 21 |
Gayle D A, Ling Z, Tong C, Landers T, Lipton J W, Carvey P M (2002). Lipopolysaccharide (LPS)-induced dopamine cell loss in culture: roles of tumor necrosis factor-alpha, interleukin-1beta, and nitric oxide. Brain Res Dev Brain Res, 133(1): 27–35
|
| 22 |
Ghatan S, Larner S, Kinoshita Y, Hetman M, Patel L, Xia Z, Youle R J, Morrison R S (2000). p38 MAP kinase mediates bax translocation in nitric oxide-induced apoptosis in neurons. J Cell Biol, 150(2): 335–347
|
| 23 |
Gomez-Lazaro M, Galindo M F, Concannon C G, Segura M F, Fernandez-Gomez F J, Llecha N, Comella J X, Prehn J H, Jordan J (2008). 6-Hydroxydopamine activates the mitochondrial apoptosis pathway through p38 MAPK-mediated, p53-independent activation of Bax and PUMA. J Neurochem, 104(6): 1599–1612
|
| 24 |
Good P F, Hsu A, Werner P, Perl D P, Olanow C W (1998). Protein nitration in Parkinson’s disease. J Neuropathol Exp Neurol, 57(4): 338–342
|
| 25 |
Hald A, Lotharius J (2005). Oxidative stress and inflammation in Parkinson’s disease: is there a causal link? Exp Neurol, 193(2): 279–290
|
| 26 |
Hartmann A, Troadec J D, Hunot S, Kikly K, Faucheux B A, Mouatt-Prigent A, Ruberg M, Agid Y, Hirsch E C (2001). Caspase-8 is an effector in apoptotic death of dopaminergic neurons in Parkinson’s disease, but pathway inhibition results in neuronal necrosis. J Neurosci, 21(7): 2247–2255
|
| 27 |
He Y, Appel S, Le W (2001). Minocycline inhibits microglial activation and protects nigral cells after 6-hydroxydopamine injection into mouse striatum. Brain Res, 909(1–2): 187–193
|
| 28 |
Herrera A J, Castaño A, Venero J L, Cano J, Machado A (2000). The single intranigral injection of LPS as a new model for studying the selective effects of inflammatory reactions on dopaminergic system. Neurobiol Dis, 7(4): 429–447
|
| 29 |
Hodara R, Norris E H, Giasson B I, Mishizen-Eberz A J, Lynch D R, Lee V M, Ischiropoulos H (2004). Functional consequences of alpha-synuclein tyrosine nitration: diminished binding to lipid vesicles and increased fibril formation. J Biol Chem, 279(46): 47746–47753
|
| 30 |
Hunot S, Boissière F, Faucheux B, Brugg B, Mouatt-Prigent A, Agid Y, Hirsch E C (1996). Nitric oxide synthase and neuronal vulnerability in Parkinson’s disease. Neuroscience, 72(2): 355–363
|
| 31 |
Hunot S, Dugas N (1999). FcepsilonRII/CD23 is expressed in Parkinson's disease and induces, in vitro, production of nitric oxide and tumor necrosis factor-alpha in glial cells. The Journal of neuroscience, 19(9): 3440–3447
|
| 32 |
Hunter R L, Cheng B, Choi D Y, Liu M, Liu S, Cass W A, Bing G (2009). Intrastriatal lipopolysaccharide injection induces parkinsonism in C57/B6 mice. J Neurosci Res, 87(8): 1913–1921
|
| 33 |
Hunter R L, Dragicevic N, Seifert K, Choi D Y, Liu M, Kim H C, Cass W A, Sullivan P G, Bing G (2007). Inflammation induces mitochondrial dysfunction and dopaminergic neurodegeneration in the nigrostriatal system. J Neurochem, 100(5): 1375–1386
|
| 34 |
Iravani M M, Kashefi K, Mander P, Rose S, Jenner P (2002). Involvement of inducible nitric oxide synthase in inflammation-induced dopaminergic neurodegeneration. Neuroscience, 110(1): 49–58
|
| 35 |
Jenner P, Olanow C W (1996). Oxidative stress and the pathogenesis of Parkinson’s disease. Neurology, 47(6 Suppl 3): S161–S170
|
| 36 |
Kim W G, Mohney R P (2000). Regional difference in susceptibility to lipopolysaccharide-induced neurotoxicity in the rat brain: role of microglia. J Neurosci, 20(16): 6309–6316
|
| 37 |
Kirik D, Rosenblad C, Björklund A (1998). Characterization of behavioral and neurodegenerative changes following partial lesions of the nigrostriatal dopamine system induced by intrastriatal 6-hydroxydopamine in the rat. Exp Neurol, 152(2): 259–277
|
| 38 |
Knott C, Stern G, Wilkin G P (2000). Inflammatory regulators in Parkinson’s disease: iNOS, lipocortin-1, and cyclooxygenases-1 and-2. Mol Cell Neurosci, 16(6): 724–739
|
| 39 |
Langston J W, Ballard P, Tetrud J W, Irwin I (1983). Chronic Parkinsonism in humans due to a product of meperidine-analog synthesis. Science, 219(4587): 979–980
|
| 40 |
Lapointe N, St-Hilaire M (2004). Rotenone induces non-specific central nervous system and systemic toxicity. FASEB journal, 18(6): 717–719
|
| 41 |
Li R, Yang L (2004). Tumor necrosis factor death receptor signaling cascade is required for amyloid-beta protein-induced neuron death. The Journal of neuroscience, 24(7): 1760–1771
|
| 42 |
Liberatore G T, Jackson-Lewis V, Vukosavic S, Mandir A S, Vila M, McAuliffe W G, Dawson V L, Dawson T M, Przedborski S (1999). Inducible nitric oxide synthase stimulates dopaminergic neurodegeneration in the MPTP model of Parkinson disease. Nat Med, 5(12): 1403–1409
|
| 43 |
Loeffler D A, DeMaggio A J, Juneau P L, Havaich M K, LeWitt P A (1994). Effects of enhanced striatal dopamine turnover in vivo on glutathione oxidation. Clin Neuropharmacol, 17(4): 370–379
|
| 44 |
Long-Smith C M, Collins L, Toulouse A, Sullivan A M, Nolan Y M (2010). Interleukin-1β contributes to dopaminergic neuronal death induced by lipopolysaccharide-stimulated rat glia in vitro. J Neuroimmunol, 226(1–2): 20–26
|
| 45 |
Lozano A M, Lang A E, Hutchison W D, Dostrovsky J O (1998). New developments in understanding the etiology of Parkinson’s disease and in its treatment. Curr Opin Neurobiol, 8(6): 783–790
|
| 46 |
Marchetti L, Klein M, Schlett K, Pfizenmaier K, Eisel U L (2004). Tumor necrosis factor (TNF)-mediated neuroprotection against glutamate-induced excitotoxicity is enhanced by N-methyl-D-aspartate receptor activation. Essential role of a TNF receptor 2-mediated phosphatidylinositol 3-kinase-dependent NF-kappa B pathway. J Biol Chem, 279(31): 32869–32881
|
| 47 |
McCoy M K, Martinez T N (2006). Blocking soluble tumor necrosis factor signaling with dominant-negative tumor necrosis factor inhibitor attenuates loss of dopaminergic neurons in models of Parkinson's disease. The Journal of neuroscience, 26(37): 9365–9375
|
| 48 |
McGeer P L, Itagaki S, Akiyama H, McGeer E G (1988a). Rate of cell death in parkinsonism indicates active neuropathological process. Ann Neurol, 24(4): 574–576
|
| 49 |
McGeer P L, Itagaki S, Boyes B E, McGeer E G (1988b). Reactive microglia are positive for HLA-DR in the substantia nigra of Parkinson’s and Alzheimer’s disease brains. Neurology, 38(8): 1285–1291
|
| 50 |
McGeer P L, Schwab C, Parent A, Doudet D (2003). Presence of reactive microglia in monkey substantia nigra years after 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine administration. Ann Neurol, 54(5): 599–604
|
| 51 |
Mogi M, Harada M, Kondo T, Riederer P, Inagaki H, Minami M, Nagatsu T (1994a). Interleukin-1 beta, interleukin-6, epidermal growth factor and transforming growth factor-alpha are elevated in the brain from parkinsonian patients. Neurosci Lett, 180(2): 147–150
|
| 52 |
Mogi M, Harada M, Riederer P, Narabayashi H, Fujita K, Nagatsu T (1994b). Tumor necrosis factor-alpha (TNF-alpha) increases both in the brain and in the cerebrospinal fluid from parkinsonian patients. Neurosci Lett, 165(1–2): 208–210
|
| 53 |
Mogi M, Togari A, Kondo T, Mizuno Y, Komure O, Kuno S, Ichinose H, Nagatsu T (2000). Caspase activities and tumor necrosis factor receptor R1 (p55) level are elevated in the substantia nigra from parkinsonian brain. J Neural Transm, 107(3): 335–341
|
| 54 |
Murray J, Taylor S W, Zhang B, Ghosh S S, Capaldi R A (2003). Oxidative damage to mitochondrial complex I due to peroxynitrite: identification of reactive tyrosines by mass spectrometry. J Biol Chem, 278(39): 37223–37230
|
| 55 |
Nagatsu T, Mogi M, Ichinose H, Togari A (2000). Changes in cytokines and neurotrophins in Parkinson’s disease. J Neural Transm Suppl, (60): 277–290
|
| 56 |
Nakamura Y (2002). Regulating factors for microglial activation. Biol Pharm Bull, 25(8): 945–953
|
| 57 |
Olanow C W, Tatton W G (1999). Etiology and pathogenesis of Parkinson’s disease. Annu Rev Neurosci, 22(1): 123–144
|
| 58 |
Pawate S, Shen Q, Fan F, Bhat N R (2004). Redox regulation of glial inflammatory response to lipopolysaccharide and interferongamma. J Neurosci Res, 77(4): 540–551
|
| 59 |
Paxinou E, Chen Q (2001). Induction of alpha-synuclein aggregation by intracellular nitrative insult. The Journal of neuroscience, 21(20): 8053–8061
|
| 60 |
Perese D A, Ulman J, Viola J, Ewing S E, Bankiewicz K S (1989). A 6-hydroxydopamine-induced selective parkinsonian rat model. Brain Res, 494(2): 285–293
|
| 61 |
Przedborski S, Chen Q, Vila M, Giasson B I, Djaldatti R, Vukosavic S, Souza J M, Jackson-Lewis V, Lee V M, Ischiropoulos H (2001). Oxidative post-translational modifications of alpha-synuclein in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of Parkinson’s disease. J Neurochem, 76(2): 637–640
|
| 62 |
Przedborski S, Levivier M, Jiang H, Ferreira M, Jackson-Lewis V, Donaldson D, Togasaki D M (1995). Dose-dependent lesions of the dopaminergic nigrostriatal pathway induced by intrastriatal injection of 6-hydroxydopamine. Neuroscience, 67(3): 631–647
|
| 63 |
Qin L, Liu Y, Wang T, Wei S J, Block M L, Wilson B, Liu B, Hong J S (2004). NADPH oxidase mediates lipopolysaccharide-induced neurotoxicity and proinflammatory gene expression in activated microglia. J Biol Chem, 279(2): 1415–1421
|
| 64 |
Ransohoff R M, Perry V H (2009). Microglial physiology: unique stimuli, specialized responses. Annu Rev Immunol, 27(1): 119–145
|
| 65 |
Shavali S, Combs C K, Ebadi M (2006). Reactive macrophages increase oxidative stress and alpha-synuclein nitration during death of dopaminergic neuronal cells in co-culture: relevance to Parkinson’s disease. Neurochem Res, 31(1): 85–94
|
| 66 |
Sherer T B, Kim J H, Betarbet R, Greenamyre J T (2003). Subcutaneous rotenone exposure causes highly selective dopaminergic degeneration and alpha-synuclein aggregation. Exp Neurol, 179(1): 9–16
|
| 67 |
Sherer T B, Richardson J R, Testa C M, Seo B B, Panov A V, Yagi T, Matsuno-Yagi A, Miller G W, Greenamyre J T (2007). Mechanism of toxicity of pesticides acting at complex I: relevance to environmental etiologies of Parkinson’s disease. J Neurochem, 100(6): 1469–1479
|
| 68 |
Tiwari M, Lopez-Cruzan M, Morgan W W, Herman B (2011). Loss of caspase-2-dependent apoptosis induces autophagy after mitochondrial oxidative stress in primary cultures of young adult cortical neurons. J Biol Chem, 286(10): 8493–8506
|
| 69 |
Vijitruth R, Liu M, Choi D Y, Nguyen X V, Hunter R L, Bing G (2006). Cyclooxygenase-2 mediates microglial activation and secondary dopaminergic cell death in the mouse MPTP model of Parkinson’s disease. J Neuroinflammation, 3(1): 6
|
| 70 |
Wang, T., Pei, Z.,
|
| 71 |
Wu D C, Jackson-Lewis V, Vila M, Tieu K, Teismann P, Vadseth C, Choi D K, Ischiropoulos H, Przedborski S (2002). Blockade of microglial activation is neuroprotective in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mouse model of Parkinson disease. J Neurosci, 22(5): 1763–1771
|
| 72 |
Wu D C, Teismann P, Tieu K, Vila M, Jackson-Lewis V, Ischiropoulos H, Przedborski S (2003). NADPH oxidase mediates oxidative stress in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine model of Parkinson’s disease. Proc Natl Acad Sci USA, 100(10): 6145–6150
|
| 73 |
Xing B, Liu M, Bing G (2007). Neuroprotection with pioglitazone against LPS insult on dopaminergic neurons may be associated with its inhibition of NF-kappaB and JNK activation and suppression of COX-2 activity. J Neuroimmunol, 192(1–2): 89–98
|
| 74 |
Xing B, Xin T, Hunter R L, Bing G (2008). Pioglitazone inhibition of lipopolysaccharide-induced nitric oxide synthase is associated with altered activity of p38 MAP kinase and PI3K/Akt. J Neuroinflammation, 5(1): 4
|
| 75 |
Zhang F, Shi J S, Zhou H, Wilson B, Hong J S, Gao H M (2010). Resveratrol protects dopamine neurons against lipopolysaccharide-induced neurotoxicity through its anti-inflammatory actions. Mol Pharmacol, 78(3): 466–477
|
| 76 |
Zhang J, Perry G, Smith M A, Robertson D, Olson S J, Graham D G, Montine T J (1999). Parkinson’s disease is associated with oxidative damage to cytoplasmic DNA and RNA in substantia nigra neurons. Am J Pathol, 154(5): 1423–1429
|
| 77 |
Zhang J, Stanton D M, Nguyen X V, Liu M, Zhang Z, Gash D, Bing G (2005). Intrapallidal lipopolysaccharide injection increases iron and ferritin levels in glia of the rat substantia nigra and induces locomotor deficits. Neuroscience, 135(3): 829–838
|
| 78 |
Zhang W, Wang T (2005). Aggregated alpha-synuclein activates microglia: a process leading to disease progression in Parkinson's disease. FASEB journal, 19(6): 533–542
|
/
| 〈 |
|
〉 |