Age-related severity of dopaminergic neurodegeneration to MPTP neurotoxicity causes motor dysfunction in C57BL/6 mice.
This study investigated the influence of advancing age on dopaminergic neuronal degeneration induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) intoxication from the perspective concerning the relationship between dopaminergic function and behavioral features. Young (10 weeks) and older (14-15 months) C57BL/6 mice were treated with one to four injections of MPTP (20 mg/kg at 2h intervals). Although young mice showed no mortality in either MPTP treatment, older mice exhibited mortality from only two injections of MPTP during the experimental period. An extensive dopaminergic cell loss was found in both the striatum and substantia nigra of older mice given one and two injections of MPTP with marked decrease in striatal dopamine (DA) levels, but not young mice. We also found a behavioral change in the tail suspension test associated with the extent of decrease in striatal DA levels in MPTP-treated older mice, but not in young mice. These results clearly present age-related vulnerability to MPTP neurotoxicity in C57BL/6 mice and strongly support our previous report showing that there is a critical threshold level of the decrement in striatal DA contents causing motor dysfunction in this mouse model of Parkinson's disease.
Research Unit for Neurological Diseases, Second Institute of New Drug Discovery, Otsuka Pharmaceutical Co., Ltd., 463-10 Kagasuno, Kawauchi-cho, Tokushima 771-0192, Japan.
Satoshi
S
Ohashi
Atsushi
A
Mori
Naoki
N
Kurihara
Yasuhide
Y
Mitsumoto
Masami
M
Nakai
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000009:adverse effects; D000367:Age Factors; D000375:Aging / Q000378:metabolism / Q000473:pathology*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000473:pathology* / Q000503:physiopathology*; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D003342:Corpus Striatum / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D018450:Disease Progression; D004298:Dopamine / Q000378:metabolism; D004409:Dyskinesia, Drug-Induced / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009410:Nerve Degeneration / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D020734:Parkinsonian Disorders / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology*; D013378:Substantia Nigra / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D004298:Dopamine