Melatonin attenuates mptp-induced neurotoxicity via preventing cdk5-mediated autophagy and SNCA/α-synuclein aggregation

Autophagy

Volumn 11, Issue 10, 2015, Pages 1745-1759

  Su, Ling Yan ^a,b   Li, Hao ^a,b   Lv, Li ^a,b   Feng, Yue Mei ^a   Li, Guo Dong ^a,b,c   Luo, Rongcan ^a   Zhou, He Jiang ^a   Lei, Xiao Guang ^a   Ma, Liang ^a,b   Li, Jia Li ^a   Xu, Lin ^a,d   Hu, Xin Tian ^a,d   Yao, Yong Gang ^a,b,d  

^a KUNMING INSTITUTE OF ZOOLOGY   (China)

^b UNIVERSITY OF CHINESE ACADEMY OF SCIENCES   (China)

^c ANHUI UNIVERSITY   (China)

^d Chinese Academy of Sciences   (China)

Author keywords

Autophagy; CDK5; Melatonin; MPTP; SNCA; TH

Indexed keywords

1,2,3,6 TETRAHYDRO 1 METHYL 4 PHENYLPYRIDINE; ALPHA SYNUCLEIN; CYCLIN DEPENDENT KINASE 5; MELATONIN; NEUROPROTECTIVE AGENT; DOPAMINE; NEUROTOXIN;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; AUTOPHAGY; BRAIN NERVE CELL; BRAIN PROTECTION; BRAIN TISSUE; CONTROLLED STUDY; DENDRITIC CELL; DOPAMINERGIC NERVE CELL; GENE SILENCING; HAPLORHINI; MALE; MOUSE; NEUROTOXICITY; NONHUMAN; PROTEIN AGGREGATION; UPREGULATION; ANIMAL; DISEASE MODEL; DRUG EFFECTS; METABOLISM; PARKINSON DISEASE; PHYSIOLOGY;

1-METHYL-4-PHENYL-1,2,3,6-TETRAHYDROPYRIDINE; ALPHA-SYNUCLEIN; ANIMALS; AUTOPHAGY; CYCLIN-DEPENDENT KINASE 5; DISEASE MODELS, ANIMAL; DOPAMINE; DOPAMINERGIC NEURONS; HAPLORHINI; MELATONIN; MICE; NEUROTOXINS; PARKINSON DISEASE;

EID: 84953873759     PISSN: 15548627     EISSN: 15548635     Source Type: Journal    
DOI: 10.1080/15548627.2015.1082020     Document Type: Article

References (76)

1. Ferrer I, Martinez A, Blanco R, Dalfo E, Carmona M. Neuropathology of sporadic Parkinson disease before the appearance of parkinsonism: preclinical Parkinson disease. J Neural Transm 2011; 118:821-39; PMID:20862500; http://dx.doi.org/10.1007/s00702-010-0482-8
2. Dawson TM, Dawson VL. Molecular pathways of neurodegeneration in Parkinson disease. Science 2003; 302:819-22; PMID:14593166; http://dx.doi.org/10.1126/science.1087753
3. Betarbet R, Sherer TB, MacKenzie G, Garcia-Osuna M, Panov AV, Greenamyre JT. Chronic systemic pesticide exposure reproduces features of Parkinson disease. Nat Neurosci 2000; 3:1301-6; PMID:11100151; http://dx.doi.org/10.1038/81834
4. Collier TJ, Kanaan NM, Kordower JH. Ageing as a primary risk factor for Parkinson disease: evidence from studies of non-human primates. Nature reviews. Neuroscience 2011; 12:359-66; PMID:21587290; http://dx.doi.org/10.1038/nrn3039
5. Braak H, Del Tredici K, Rub U, de Vos RA, Jansen Steur EN, Braak E. Staging of brain pathology related to sporadic Parkinson disease. Neurobiol Aging 2003; 24:197-211; PMID:12498954; http://dx.doi.org/10.1016/S0197-4580(02)00065-9
6. Burns RS, Chiueh CC, Markey SP, Ebert MH, Jacobowitz DM, Kopin IJ. A primate model of parkinsonism: selective destruction of dopaminergic neurons in the pars compacta of the substantia nigra by N-methyl-4- phenyl-1,2,3,6-tetrahydropyridine. Proc Natl Acad Sci U S A 1983; 80:4546-50; PMID:6192438; http://dx.doi.org/10.1073/pnas.80.14.4546
7. Bandopadhyay R, de Belleroche J. Pathogenesis of Parkinson disease: emerging role of molecular chaperones. Trends Mol Med 2009; 16:27-36; PMID:20036196; http://dx.doi.org/10.1016/j.molmed.2009.11.004
8. Przedborski S, Jackson-Lewis V, Naini AB, Jakowec M, Petzinger G, Miller R, Akram M. The parkinsonian toxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP): a technical review of its utility and safety. J Neurochem 2001; 76:1265-74; PMID:11238711; http://dx.doi.org/10.1046/j.1471-4159.2001.00183.x
9. Lang AE, Lozano AM. Parkinson disease. First of two parts. N Engl J Med 1998; 339:1044-53; PMID:9761807; http://dx.doi.org/10.1056/NEJM199810083391506
10. Gong X, Tang X, Wiedmann M, Wang X, Peng J, Zheng D, Blair LA, Marshall J, Mao Z. Cdk5-mediated inhibition of the protective effects of transcription factor MEF2 in neurotoxicity-induced apoptosis. Neuron 2003; 38:33-46; PMID:12691662; http://dx.doi.org/10.1016/S0896-6273(03)00191-0
11. Huang E, Qu D, Zhang Y, Venderova K, Haque ME, Rousseaux MW, Slack RS, Woulfe JM, Park DS. The role of Cdk5-mediated apurinic/apyrimidinic endonuclease 1 phosphorylation in neuronal death. Nat Cell Biol 2010; 12:563-71; PMID:20473298; http://dx.doi.org/10.1038/ncb2058
12. Smith PD, Crocker SJ, Jackson-Lewis V, Jordan- Sciutto KL, Hayley S, Mount MP, O’Hare MJ, Callaghan S, Slack RS, Przedborski S, et al. Cyclin-dependent kinase 5 is a mediator of dopaminergic neuron loss in a mouse model of Parkinson disease. Proc Natl Acad Sci U S A 2003; 100:13650-5; PMID:14595022; http://dx.doi.org/10.1073/pnas.2232515100
13. Tsai LH, Delalle I, Caviness VS Jr, Chae T, Harlow E. p35 is a neural-specific regulatory subunit of cyclin-dependent kinase 5. Nature 1994; 371:419-23; PMID:8090221; http://dx.doi.org/10.1038/371419a0
14. Wen Z, Shu Y, Gao C, Wang X, Qi G, Zhang P, Li M, Shi J, Tian B. CDK5-mediated phosphorylation and autophagy of RKIP regulate neuronal death in Parkinson disease. Neurobiol Aging 2014; 35:2870-80; PMID:25104559; http://dx.doi.org/10.1016/j.neurobiolaging.2014.05.034
15. Tang X, Wang X, Gong X, Tong M, Park D, Xia Z, Mao Z. Cyclin-dependent kinase 5 mediates neurotoxin- induced degradation of the transcription factor myocyte enhancer factor 2. J Neurosci 2005; 25:4823-34; PMID:15888658; http://dx.doi.org/10.1523/JNEUROSCI.1331-05.2005
16. Qu D, Rashidian J, Mount MP, Aleyasin H, Parsanejad M, Lira A, Haque E, Zhang Y, Callaghan S, Daigle M, et al. Role of Cdk5-mediated phosphorylation of Prx2 in MPTP toxicity and Parkinson disease. Neuron 2007; 55:37-52; PMID:17610816; http://dx.doi.org/10.1016/j.neuron.2007.05.033
17. Mizushima N, Yoshimori T, Levine B. Methods in mammalian autophagy research. Cell 2010; 140:313-26; PMID:20144757; http://dx.doi.org/10.1016/j.cell.2010.01.028
18. Klionsky DJ, Abdalla FC, Abeliovich H, Abraham RT, Acevedo-Arozena A, Adeli K, Agholme L, Agnello M, Agostinis P, Aguirre-Ghiso JA, et al. Guidelines for the use and interpretation of assays for monitoring autophagy. Autophagy 2012; 8:445-544; PMID:22966490; http://dx.doi.org/10.4161/auto.19496
19. Mizushima N, Yoshimori T. How to interpret LC3 immunoblotting. Autophagy 2007; 3:542-5; PMID:17611390; http://dx.doi.org/10.4161/auto.4600
20. Levine B, Kroemer G. Autophagy in the pathogenesis of disease. Cell 2008; 132:27-42; PMID:18191218; http://dx.doi.org/10.1016/j.cell.2007.12.018
21. Cheung ZH, Ip NY. Autophagy deregulation in neurodegenerative diseases - recent advances and future perspectives. J Neurochem 2011; 118:317-25; PMID:21599666; http://dx.doi.org/10.1111/j.1471-4159.2011.07314.x
22. Rubinsztein DC, DiFiglia M, Heintz N, Nixon RA, Qin ZH, Ravikumar B, Stefanis L, Tolkovsky A. Autophagy and its possible roles in nervous system diseases, damage and repair. Autophagy 2005; 1:11-22; PMID:16874045; http://dx.doi.org/10.4161/auto.1.1.1513
23. Zhu JH, Guo F, Shelburne J, Watkins S, Chu CT. Localization of phosphorylated ERK/MAP kinases to mitochondria and autophagosomes in Lewy body diseases. Brain Pathol 2003; 13:473-81; PMID:14655753; http://dx.doi.org/10.1111/j.1750-3639.2003.tb00478.x
24. Anglade P, Vyas S, Javoy-Agid F, Herrero MT, Michel PP, Marquez J, Mouatt-Prigent A, Ruberg M, Hirsch EC, Agid Y. Apoptosis and autophagy in nigral neurons of patients with Parkinson disease. Histol Histopathol 1997; 12:25-31; PMID:9046040
25. Dehay B, Bove J, Rodriguez-Muela N, Perier C, Recasens A, Boya P, Vila M. Pathogenic lysosomal depletion in Parkinson disease. J Neurosci 2010; 30:12535-44; PMID:20844148; http://dx.doi.org/10.1523/JNEUROSCI.1920-10.2010
26. Koh H, Chung J. PINK1 and Parkin to control mitochondria remodeling. Anat Cell Biol 2010; 43:179-84; PMID:21212857; http://dx.doi.org/10.5115/acb.2010.43.3.179
27. Cuervo AM, Stefanis L, Fredenburg R, Lansbury PT, Sulzer D. Impaired degradation of mutant a-synuclein by chaperone-mediated autophagy. Science 2004; 305:1292-5; PMID:15333840; http://dx.doi.org/10.1126/science.1101738
28. Vogiatzi T, Xilouri M, Vekrellis K, Stefanis L. Wild type a-synuclein is degraded by chaperonemediated autophagy and macroautophagy in neuronal cells. J Biol Chem 2008; 283:23542-56; PMID:18566453; http://dx.doi.org/10.1074/jbc.M801992200
29. Yang Q, She H, Gearing M, Colla E, Lee M, Shacka JJ, Mao Z. Regulation of neuronal survival factor MEF2D by chaperone-mediated autophagy. Science 2009; 323:124-7; PMID:19119233; http://dx.doi.org/10.1126/science.1166088
30. Nopparat C, Porter JE, Ebadi M, Govitrapong P. One- Methyl-4-phenylpyridinium-induced cell death via autophagy through a Bcl ¡ 2/Beclin 1 complex-dependent pathway. Neurochem Res 2014; 39:225-32; PMID:24326530; http://dx.doi.org/10.1007/s11064-013-1208-8
31. Wong AS, Lee RH, Cheung AY, Yeung PK, Chung SK, Cheung ZH, Ip NY. Cdk5-mediated phosphorylation of endophilin B1 is required for induced autophagy in models of Parkinson disease. Nat Cell Biol 2011; 13:568-79; PMID:21499257; http://dx.doi.org/10.1038/ncb2217
32. Singhal NK, Srivastava G, Agrawal S, Jain SK, Singh MP. Melatonin as a neuroprotective agent in the rodent models of Parkinson disease: is it all set to irrefutable clinical translation? Mol Neurobiol 2012; 45:186-99; PMID:22198804; http://dx.doi.org/10.1007/s12035-011-8225-x
33. Hardeland R. Melatonin and the theories of aging: a critical appraisal of melatonin’s role in antiaging mechanisms. J Pineal Res 2013; 55:325-56; PMID:24112071; http://dx.doi.org/10.1111/jpi.12090
34. Rodriguez C, Mayo JC, Sainz RM, Antolin I, Herrera F, Martin V, Reiter RJ. Regulation of antioxidant enzymes: a significant role for melatonin. J Pineal Res 2004; 36:1-9; PMID:14675124; http://dx.doi.org/10.1046/j.1600-079X.2003.00092.x
35. Vega-Naredo I, Caballero B, Sierra V, Garcia-Macia M, de Gonzalo-Calvo D, Oliveira PJ, Rodriguez- Colunga MJ, Coto-Montes A. Melatonin modulates autophagy through a redox-mediated action in female Syrian hamster Harderian gland controlling cell types and gland activity. J Pineal Res 2011; 52:80-92; PMID:21771054; http://dx.doi.org/10.1111/j.1600-079X.2011.00922.x
36. Khaldy H, Escames G, Leon J, Bikjdaouene L, Acuna- Castroviejo D. Synergistic effects of melatonin and deprenyl against MPTP-induced mitochondrial damage and DA depletion. Neurobiol Aging 2003; 24:491-500; PMID:12600724; http://dx.doi.org/10.1016/S0197-4580(02)00133-1
37. Chen ST, Chuang JI, Hong MH, Li EI. Melatonin attenuates MPPC-induced neurodegeneration and glutathione impairment in the nigrostriatal dopaminergic pathway. J Pineal Res 2002; 32:262-9; PMID:11982797; http://dx.doi.org/10.1034/j.1600-079X.2002.01871.x
38. Li XJ, Gu J, Lu SD, Sun FY. Melatonin attenuates MPTP-induced dopaminergic neuronal injury associated with scavenging hydroxyl radical. J Pineal Res 2002; 32:47-52; PMID:11841600; http://dx.doi.org/10.1034/j.1600-079x.2002.10831.x
39. Absi E, Ayala A, Machado A, Parrado J. Protective effect of melatonin against the 1-methyl-4-phenylpyridinium- induced inhibition of complex I of the mitochondrial respiratory chain. J Pineal Res 2000; 29:40-7; PMID:10949539; http://dx.doi.org/10.1034/j.1600-079X.2000.290106.x
40. Jin BK, Shin DY, Jeong MY, Gwag MR, Baik HW, Yoon KS, Cho YH, Joo WS, Kim YS, Baik HH. Melatonin protects nigral dopaminergic neurons from 1-methyl-4-phenylpyridinium (MPPC) neurotoxicity in rats. Neurosci Lett 1998; 245:61-4; PMID:9605485; http://dx.doi.org/10.1016/S0304-3940(98)00170-0
41. Chuang JI, Chen TH. Effect of melatonin on temporal changes of reactive oxygen species and glutathione after MPP(C) treatment in human astrocytoma U373MG cells. J Pineal Res 2004; 36:117-25; PMID:14962063; http://dx.doi.org/10.1046/j.1600-079X.2003.00107.x
42. Thomas B, Mohanakumar KP. Melatonin protects against oxidative stress caused by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine in the mouse nigrostriatum. J Pineal Res 2004; 36:25-32; PMID:14675127; http://dx.doi.org/10.1046/j.1600-079X.2003.00096.x
43. Ortiz GG, Crespo-Lopez ME, Moran-Moguel C, Garcia JJ, Reiter RJ, Acuna-Castroviejo D. Protective role of melatonin against MPTP-induced mouse brain cell DNA fragmentation and apoptosis in vivo. Neuro Endocrinol Lett 2001; 22:101-8; PMID:11335886; http://dx.doi.org/NEL220201A04.
44. Capitelli C, Sereniki A, Lima MM, Reksidler AB, Tufik S, Vital MA. Melatonin attenuates tyrosine hydroxylase loss and hypolocomotion in MPTP-lesioned rats. Eur J Pharmacol 2008; 594:101-8; PMID:18674531; http://dx.doi.org/10.1016/j.ejphar.2008.07.022
45. Feng YM, Jia YF, Su LY, Wang D, Lv L, Xu L, Yao YG. Decreased mitochondrial DNA copy number in the hippocampus and peripheral blood during opiate addiction is mediated by autophagy and can be salvaged by melatonin. Autophagy 2013; 9:1395-406; PMID:23800874; http://dx.doi.org/10.4161/auto.25468
46. Alvira D, Tajes M, Verdaguer E, Acuna-Castroviejo D, Folch J, Camins A, Pallas M. Inhibition of the cdk5/ p25 fragment formation may explain the antiapoptotic effects of melatonin in an experimental model of Parkinson disease. J Pineal Res 2006; 40:251-8; PMID:16499562; http://dx.doi.org/10.1111/j.1600-079X.2005.00308.x
47. Patrick GN, Zukerberg L, Nikolic M, de la Monte S, Dikkes P, Tsai LH. Conversion of p35 to p25 deregulates Cdk5 activity and promotes neurodegeneration. Nature 1999; 402:615-22; PMID:10604467; http://dx.doi.org/10.1038/45159
48. Nopparat C, Porter JE, Ebadi M, Govitrapong P. The mechanism for the neuroprotective effect of melatonin against methamphetamine-induced autophagy. J Pineal Res 2010; 49:382-9; PMID:20738755; http://dx.doi.org/10.1111/j.1600-079X.2010.00805.x
49. Stefanis L. a-Synuclein in Parkinson disease. Cold Spring Harb Perspect Med 2012; 2:a009399; PMID:22355802; http://dx.doi.org/10.1101/cshperspect.a009399
50. Vekrellis K, Stefanis L. Targeting intracellular and extracellular a-synuclein as a therapeutic strategy in Parkinson disease and other synucleinopathies. Expert Opin Ther Targets 2012; 16:421-32; PMID:22480256; http://dx.doi.org/10.1517/14728222.2012.674111
51. Jakowec MW, Petzinger GM. One-methyl-4-phenyl- 1,2,3,6-tetrahydropyridine-lesioned model of parkinson’s disease, with emphasis on mice and nonhuman primates. Comp Med 2004; 54:497-513;
52. PMID:15575363
53. Xilouri M, Stefanis L. Autophagic pathways in Parkinson disease and related disorders. Expert Rev Mol Med 2011; 13:e8; PMID:21418705; http://dx.doi.org/10.1017/S1462399411001803
54. Hollerhage M, Goebel JN, de Andrade A, Hildebrandt T, Dolga A, Culmsee C, Oertel WH, Hengerer B, Hoglinger GU. Trifluoperazine rescues human dopaminergic cells from wild-type a-synuclein-induced toxicity. Neurobiol Aging 2014; 35:1700-11; PMID:24559643; http://dx.doi.org/10.1016/j.neurobiolaging.2014.01.027
55. Pan T, Kondo S, Zhu W, Xie W, Jankovic J, Le W. Neuroprotection of rapamycin in lactacystin-induced neurodegeneration via autophagy enhancement. Neurobiol Dis 2008; 32:16-25; PMID:18640276; http://dx.doi.org/10.1016/j.nbd.2008.06.003
56. Xiong N, Xiong J, Jia M, Liu L, Zhang X, Chen Z, Huang J, Zhang Z, Hou L, Luo Z, et al. The role of autophagy in Parkinson disease: rotenone-based modeling. Behav Brain Funct 2013; 9:13; PMID:23497442; http://dx.doi.org/10.1186/1744-9081-9-13
57. Plowey ED, Cherra SJ, Liu YJ, Chu CT. Role of autophagy in G2019S-LRRK2-associated neurite shortening in differentiated SH-SY5Y cells. J Neurochem 2008; 105:1048-56; PMID:18182054; http://dx.doi.org/10.1111/j.1471-4159.2008.05217.x
58. Cherra SJ, Steer E, Gusdon AM, Kiselyov K, Chu CT. Mutant LRRK2 elicits calcium imbalance and depletion of dendritic mitochondria in neurons. Am J Pathol 2013; 182:474-84; PMID:23231918; http://dx.doi.org/10.1016/j.ajpath.2012.10.027
59. Choubey V, Safiulina D, Vaarmann A, Cagalinec M, Wareski P, Kuum M, Zharkovsky A, Kaasik A. Mutant A53T a-synuclein induces neuronal death by increasing mitochondrial autophagy. J Biol Chem 2011; 286:10814-24; PMID:21252228; http://dx.doi.org/10.1074/jbc.M110.132514
60. Li L, Wang X, Fei X, Xia L, Qin Z, Liang Z. Parkinson disease involves autophagy and abnormal distribution of cathepsin L. Neurosci Lett 2011; 489:62-7; PMID:21134415; http://dx.doi.org/10.1016/j.neulet.2010.11.068
61. Chu CT, Plowey ED, Dagda RK, Hickey RW, Cherra SJ, Clark RS. Autophagy in neurite injury and neurodegeneration: in vitro and in vivo models. Methods Enzymol 2009; 453:217-49; PMID:19216909; http://dx.doi.org/10.1016/S0076-6879(08)04011-1
62. Chang CF, Huang HJ, Lee HC, Hung KC, Wu RT, Lin AM. Melatonin attenuates kainic acid-induced neurotoxicity in mouse hippocampus via inhibition of autophagy and a-synuclein aggregation. J Pineal Res 2012; 52:312-21; PMID:22212051; http://dx.doi.org/10.1111/j.1600-079X.2011.00945.x
63. Ma J, Shaw VE, Mitrofanis J. Does melatonin help save dopaminergic cells in MPTP-treated mice? Parkinsonism & Related Disorders. 2009; 15:307-14; PMID:18793863; http://dx.doi.org/10.1016/j.parkreldis.2008.07.008
64. Singhal NK, Srivastava G, Patel DK, Jain SK, Singh MP. Melatonin or silymarin reduces maneb- and paraquat- induced Parkinson disease phenotype in the mouse. J Pineal Res 2011; 50:97-109; PMID:20964710; http://dx.doi.org/10.1111/j.1600-079X.2010.00819.x
65. Jenner P. Oxidative mechanisms in nigral cell death in Parkinson disease. Mov Disord 1998; 13 Suppl 1:24-34; PMID:9613715
66. Danielson SR, Andersen JK. Oxidative and nitrative protein modifications in Parkinson disease. Free Radic Biol Med 2008; 44:1787-94; PMID:18395015; http://dx.doi.org/10.1016/j.freeradbiomed.2008.03.005
67. Vicencio JM, Lavandero S, Szabadkai G. Ca2C ,autophagy and protein degradation: thrown off balance in neurodegenerative disease. Cell Calcium 2010; 47:112-21; PMID:20097418; http://dx.doi.org/10.1016/j.ceca.2009.12.013
68. Smith PD, Mount MP, Shree R, Callaghan S, Slack RS, Anisman H, Vincent I, Wang X, Mao Z, Park DS. Calpain-regulated p35/cdk5 plays a central role in dopaminergic neuron death through modulation of the transcription factor myocyte enhancer factor 2. J Neurosci 2006; 26:440-7; PMID:16407541; http://dx.doi.org/10.1523/JNEUROSCI.2875-05.2006
69. Graham WC, Robertson RG, Sambrook MA, Crossman AR. Injection of excitatory amino acid antagonists into the medial pallidal segment of a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) treated primate reverses motor symptoms of parkinsonism. Life Sci 1990; 47:PL91-7; PMID:2250573; http://dx.doi.org/10.1016/0024-3205(90)90376-3
70. Smith RD, Zhang Z, Kurlan R, McDermott M, Gash DM. Developing a stable bilateral model of parkinsonism in rhesus monkeys. Neuroscience 1993; 52:7-16; PMID:8433810; http://dx.doi.org/10.1016/0306-4522(93)90176-G
71. Ko WK, Pioli E, Li Q, McGuire S, Dufour A, Sherer TB, Bezard E, Facheris MF. Combined fenobam and amantadine treatment promotes robust antidyskinetic effects in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned primate model of Parkinson disease. Mov Disord 2014; 29:772-9; PMID:24610195; http://dx.doi.org/10.1002/mds.25859
72. Kelly MA, Rubinstein M, Phillips TJ, Lessov CN, Burkhart-Kasch S, Zhang G, Bunzow JR, Fang Y, Gerhardt GA, Grandy DK, et al. Locomotor activity in D2 dopamine receptor-deficient mice is determined by gene dosage, genetic background, and developmental adaptations. J Neurosci 1998; 18:3470-9; PMID:9547254
73. Ojha RP, Rastogi M, Devi BP, Agrawal A, Dubey GP. Neuroprotective effect of curcuminoids against inflammation-mediated dopaminergic neurodegeneration in the MPTP model of Parkinson disease. J Neuroimmune Pharmacol 2012; 7:609-18; PMID:22527634; http://dx.doi.org/10.1007/s11481-012-9363-2
74. Manna SS, Umathe SN. Involvement of transient receptor potential vanilloid type 1 channels in the proconvulsant effect of anandamide in pentylenetetrazoleinduced seizures. Epilepsy Res 2012; 100:113-24; PMID:22386872; http://dx.doi.org/10.1016/j.eplepsyres.2012.02.003
75. Paxinos G, Franklin KBJ. The mouse brain in stereotaxic coordinates. 2nd ed (Academic Press, 2001).
76. Schacht V, Kern JS. Basics of immunohistochemistry. J Invest Dermatol 2015; 135:e30; PMID:25666678; http://dx.doi.org/10.1038/jid.2014.541