書誌： Neuroscience Letters , 2012
Neuroscience Letters 506 (2012) 79–83
Ken-ichi Hashimoto, Shuichi Ueda, Ayuka Ehara, Shin-ichi Sakakibara, Kanji Yoshimoto, Koichi Hirata
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-relateddegeneration ofthe dopaminergic system. For up to 9months afterweaning, zi/zi rats had ad libitumaccessto drinking water containing melatonin. Chronic treatment with melatonin attenuated the decreases ofdopamine and its metabolite in zi/zi rat caudate-putamen (CPU). Immunohistochemistry for tyrosinehydroxylase (TH) was consistent with neurochemical data in the CPU and demonstrated substantialsparing 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-inflammatorycytokines (IL-1ˇ and TNF-˛) 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-1ˇ and TNF-˛ mRNA expressions were significantly increased in bothareas of 3-month-old zi/zi rats, whereas there was a significant decrease in CAT mRNA expression inthe striatum of 6-month-old zi/zi rat as compared to age-matched controls. With the exception of thehigh TNF-˛ mRNA expression in 3-month-old zi/zi midbrains, chronic treatment of melatonin attenuatedexpressional changes of IL-1ˇ, CAT, SOD1, and GPx1. These results suggestthat besides its direct scavengereffects, chronic melatonin treatment provides a neuroprotective effect against dopaminergic degeneration by suppressing pro-inflammatory cytokines and up-regulating anti-oxidant enzyme expression.