Neuroprotective effects of melatonin on the nigrostriatal dopamine system in the zitter rat

Ken ichi Hashimoto, Shuichi Ueda*, Ayuka Ehara, Shin ichi Sakakibara, Kanji Yoshimoto, Koichi Hirata


研究成果: Article査読

17 被引用数 (Scopus)


Melatonin has ubiquitous actions, both as a direct free-radical scavenger and as an indirect anti-oxidant. The present study examined in vivo neuroprotective effects of melatonin on the nigrostriatal dopaminergic system in zitter (zi/. zi) rat, which displays abnormal metabolism of superoxide leading to age-related degeneration of the dopaminergic system. For up to 9 months after weaning, zi/. zi rats had ad libitum access to drinking water containing melatonin. Chronic treatment with melatonin attenuated the decreases of dopamine and its metabolite in zi/. zi rat caudate-putamen (CPU). Immunohistochemistry for tyrosine hydroxylase (TH) was consistent with neurochemical data in the CPU and demonstrated substantial sparing of the reduction of TH-immunoreactive neurons in the substantia nigra pars compacta. Quantitative polymerase chain reaction (qPCR) was performed to analyze mRNA expressions of pro-inflammatory cytokines (IL-1β and TNF-α) and the anti-oxidant enzymes (catalase (CAT), superoxide dismutase (SOD) 1 and 2, and glutathione peroxidase (GPx1)) in the striatum and midbrain in order to examine the neuroprotective effect of melatonin. IL-1β and TNF-α mRNA expressions were significantly increased in both areas of 3-month-old zi/. zi rats, whereas there was a significant decrease in CAT mRNA expression in the striatum of 6-month-old zi/. zi rat as compared to age-matched controls. With the exception of the high TNF-α mRNA expression in 3-month-old zi/. zi midbrains, chronic treatment of melatonin attenuated expressional changes of IL-1β, CAT, SOD1, and GPx1. These results suggest that besides its direct scavenger effects, chronic melatonin treatment provides a neuroprotective effect against dopaminergic degeneration by suppressing pro-inflammatory cytokines and up-regulating anti-oxidant enzyme expression.

ジャーナルNeuroscience Letters
出版ステータスPublished - 2012 1月 6

ASJC Scopus subject areas

  • 神経科学一般


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