Damage to the nigrostriatal system in the MPTP-treated SAMP8 mouse.
Application of aged animals to studies of Parkinson's disease (PD) will be beneficial to improve the understanding of its pathogenesis. The senescence-accelerated mouse prone8 (SAMP8) mouse has an early onset of senility and a short life span, characterized by learning and memory impairment, and affective disturbance in the aging process. There is no animal currently being used as a PD model that exhibits these characteristics. Application of the SAMP8 mouse to PD research may have several merits. For the first time, we have investigated damage of the nigrostriatal system in the SAMP8 mouse induced by 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP). Male SAMP8 mice (12 weeks) were treated with four subcutaneous injections of MPTP (20mg/kg at 2h intervals): spontaneous activity decreased significantly after the third injection, and recovered 48h after the first injection. In MPTP-SAMP8 mice, the tyrosine hydroxylase (TH)-positive neuronal loss at 6h (7.06%), 24h (12.79%), 3 days (22.49%), and 8 days (42.39%), while striatal dopamine (DA) levels decreased at 6h by 79.09%, at 24h by 80.33%, at 3 days by 83.86%, and at 8 days by 80.14%. These results indicated that there were marked decreases in striatal DA levels and a loss of dopaminergic neurons in the substantia nigra, with the behavior change following shortly thereafter, in MPTP-SAMP8 mice. On the basis of the current findings, the SAMP8 mouse is also vulnerable to neurotoxic effects of MPTP. These data suggest that the SAMP8 mouse may be utilized in PD research.
Liu
Jing
J
Department of Neurology, The First Hospital of Hebei Medical University, Brain Aging and Cognitive Neuroscience Laboratory of Hebei Province, Shijiazhuang 050017, China.
Wang
Yan-Yong
YY
Liu
Li
L
Wang
Quan-Dong
QD
Yuan
Zhen-Yun
ZY
Zhang
Zhong-Xia
ZX
Gu
Ping
P
Wang
Ming-Wei
MW
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000494:pharmacology*; D000375:Aging; D000704:Analysis of Variance; D000818:Animals; D016923:Cell Death; D003342:Corpus Striatum / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D007150:Immunohistochemistry; D051379:Mice; D008806:Mice, Inbred AKR; D008822:Mice, Transgenic; D009043:Motor Activity / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D009498:Neurotoxins / Q000494:pharmacology / Q000633:toxicity; D010300:Parkinson Disease / Q000473:pathology / Q000503:physiopathology; D020734:Parkinsonian Disorders / Q000473:pathology / Q000503:physiopathology; D013378:Substantia Nigra / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D009498:Neurotoxins; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine