Microglial activation and age-related dopaminergic neurodegeneration in MPTP-treated SAMP8 mice.
Senescence-accelerated mouse prone 8 (SAMP8) has an early onset of senility and a shorter life span, providing with cognitive impairment. Contrasted with C57BL/6 mouse, which is most commonly used in the study of Parkinson's disease (PD), SAMP8 needs shorter period of breeding and might be good candidate for the investigation of cognitive impairment in PD. Studies had shown the increase of sensibility to 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) with aging in C57BL/6 mouse. However, the sensitivity of MPTP neurotoxicity depends on the strains of animal and the exact mechanisms of the progression of PD promoted by aging is lack of consensus. Here, we showed after MPTP injection, the spontaneous activity of both young (3-month-old) and old (6-month-old) SAMP8 decreased dramatically, and the old mice required longer recovery time. Immunohistochemical and immunoblot analysis revealed that old mice displayed significant reductions in the dopaminergic neuron numbers and tyrosine hydroxylase (TH) protein. Microglia protein (CD11b) in the striatum of old mice increased more pronouncedly than that in the young mice from 24 h to 3 days. Inducible nitric oxide synthase (iNOS) in the striatum remarkably increased, however, no discernible difference between the two groups was found. These results suggested that the sensibility to MPTP increased with aging in SAMP8. A greater increase of microglial activation in old mice may be a possible mechanism to explain how advancing age predisposes the dopamine system to parkinsonism. The MPTP-SAMP8 model will start a new consideration for the study of PD.
Liu
Jing
J
The First Hospital of Hebei Medical University, Brain Aging and Cognitive Neuroscience Laboratory of Hebei Province, Shijiazhuang, China.
Wang
Ming-Wei
MW
Gu
Ping
P
Ma
Qin-Ying
QY
Wang
Yan-Yong
YY
Geng
Yuan
Y
Yuan
Zhen-Yun
ZY
Cui
Dong-Sheng
DS
Zhang
Zhong-Xia
ZX
Ma
Lin
L
Zhang
Bao-Hua
BH
Zhou
Mei-Gang
MG
Zhu
Ai-Ping
AP
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000375:Aging / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D039481:CD11b Antigen / Q000378:metabolism; D002452:Cell Count; D003342:Corpus Striatum / Q000378:metabolism / Q000473:pathology; D004298:Dopamine / Q000378:metabolism*; D008297:Male; D008636:Mesencephalon / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008817:Mice, Mutant Strains; D017628:Microglia / Q000378:metabolism* / Q000473:pathology; D009043:Motor Activity; D009410:Nerve Degeneration / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D020734:Parkinsonian Disorders / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D013997:Time Factors; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D039481:CD11b Antigen; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine