Biochemical, behavioral and immunohistochemical alterations in MPTP-treated mouse model of Parkinson's disease

• Published in: Pharmacology, biochemistry and behavior biochemistry and behavior, 2004-05, Vol.78 (1), p.143-153
• Main Authors: Kurosaki, Rumiko, Muramatsu, Yasuko, Kato, Hiroyuki, Araki, Tsutomu
• Format: Article
• Language: English
• Subjects: Animals; Behavior; Biological and medical sciences; Corpus Striatum - chemistry; Corpus Striatum - metabolism; Dopamine; Free radicals; Fundamental and applied biological sciences. Psychology; Immunohistochemistry; Male; Medical sciences; Mice; Mice, Inbred C57BL; MPTP; MPTP Poisoning - metabolism; Neuropharmacology; Pharmacology. Drug treatments; Psychology. Psychoanalysis. Psychiatry; Psychology. Psychophysiology; Striatum; Substantia nigra; Substantia Nigra - chemistry; Substantia Nigra - metabolism
• ISSN: 0091-3057; 1873-5177
• DOI: 10.1016/j.pbb.2004.03.006

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.