Effects of cysteamine on MPTP-induced dopaminergic neurodegeneration in mice.
Cysteamine is a degradation product of the amino acid cysteine and a reduced form of cystamine. Cysteamine exhibits strong antioxidant activity and has been implicated in the treatment of neurodegenerative disorders such as Huntington's disease. In the present study, we investigated whether cysteamine confers protection against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)-induced toxicity in the dopaminergic neurons in a mouse model for Parkinson's disease (PD). The loss of dopaminergic (DA) neurons and reduction in striatal DA concentrations induced by MPTP was ameliorated to a significant extent by pretreatment with low (20mg/kg/day), but not high (75mg/kg/day), dose of cysteamine 4days prior to and subsequently along with the MPTP treatment. Consistently, the increased production of pro-oxidants, such as reactive oxygen species (ROS) and malondialdehyde (MDA), was significantly suppressed by low dose of cysteamine. Conversely, the reduction in GSH level caused by MPTP exposure was significantly attenuated by pretreatment of cysteamine. In addition, the inhibited secretion of the brain-derived neurotrophic factor (BDNF) by neurons derived from substantia nigra pars compact (SNpc) of MPTP-treated mice was significantly restored by cysteamine administration. Our results demonstrate that cysteamine at low dose confers potent neuroprotection against MPTP-induced toxicity of dopaminergic neurons, and may become a potential therapeutic strategy for PD.
Sun
Linjuan
L
Department of Neurobiology and Neurology, Key Laboratory for Neurodegenerative Diseases of Ministry of Education, Xuanwu Hospital of Capital Medical University, #45 Changchun Street, Beijing 100053, China.
Xu
Shengli
S
Zhou
Ming
M
Wang
Chaodong
C
Wu
Yanchuan
Y
Chan
Piu
P
D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000187:drug effects / Q000378:metabolism; D003543:Cysteamine / Q000494:pharmacology* / Q000627:therapeutic use; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009410:Nerve Degeneration / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D020734:Parkinsonian Disorders / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D017382:Reactive Oxygen Species / Q000378:metabolism; D013378:Substantia Nigra / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D016896:Treatment Outcome
D019208:Brain-Derived Neurotrophic Factor; D018696:Neuroprotective Agents; D017382:Reactive Oxygen Species; D008315:Malondialdehyde; D003543:Cysteamine; D005978:Glutathione; D004298:Dopamine