著者
榊原伸一
所属
題材
生体
被検体
ラット
データ収集方法
実験
専門分野
分子生物学
評価指標
生理指標
キーワード
neuroprotectionmelatoninPD modeloxidative stressdegenerationdopamine
概要

書誌: Neuroscience Letters , 2012

Hashimoto K, Ueda S, Ehara A, Sakakibara S, Yoshimoto K, Hirata K. (2012). Neurosci Lett. 506:79-83.

abstract 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-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 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-˛ mRNA expression in 3-month-old zi/zi midbrains, chronic treatment of melatonin attenuated expressional changes of IL-1ˇ, 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. 

Keywords: Oxidative stress, Dopamine, Melatonin, Neuroprotection, Degeneration, PD model 

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2015年02月02日 00:06
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