Biochemical, behavioral and immunohistochemical alterations in MPTP-treated mouse model of Parkinson's disease.
The biochemical, behavioral and immunohistochemical manifestations were investigated in mice subjected to four experimental schedules with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) hydrochloride treatment. The mice were treated intraperitoneally with MPTP (20 mg/kg in saline) four times a day at 2-h intervals showed severe and persistent depletions of dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in the striatum and behavioral deficits, as compared with those (1) treated with MPTP (15 mg/kg in saline ip) once a day for 14 consecutive days; (2) MPTP (30 mg/kg in saline ip) twice a day for five consecutive days; and (3) MPTP (10 mg/kg in saline ip) four times a day at 1-h intervals for two consecutive days. The immunohistochemical study has shown that the acute treatment with MPTP caused severe loss of tyrosine hydroxylase (TH)- and dopamine transporter (DAT)-immunoreactive dopaminergic neurons and marked increase in glial fibrillary acidic protein (GFAP)-immunoreactive astrocytes in the striatum and the substantia nigra. Thus acute treatment of mice with MPTP was accompanied by sustained nigral degeneration and motor abnormalities. Furthermore, our results with Cu/Zn-superoxide dismutase (Cu/Zn-SOD) and manganese superoxide dismutase (Mn-SOD) immunostainings suggest that altered capacity of free radicals quenching may play a key role in the development of the neurons and interneuron damage after MPTP neurotoxicity. Thus, our findings provide valuable information on age-related disease progression and mechanisms of neurodegeneration.
Kurosaki
Rumiko
R
Department of Drug Metabolism and Therapeutics, Graduate School and Faculty of Pharmaceutical Sciences, The University of Tokushima, Tokushima, 1-78, Sho-machi, Tokushima 770-8505, Japan.
Muramatsu
Yasuko
Y
Kato
Hiroyuki
H
Araki
Tsutomu
T
D000818:Animals; D003342:Corpus Striatum / Q000737:chemistry* / Q000378:metabolism*; D007150:Immunohistochemistry; D020267:MPTP Poisoning / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D013378:Substantia Nigra / Q000737:chemistry* / Q000378:metabolism*