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

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

    Research output: Contribution to journalArticle

    11 Citations (Scopus)

    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-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.

    Original languageEnglish
    Pages (from-to)79-83
    Number of pages5
    JournalNeuroscience Letters
    Volume506
    Issue number1
    DOIs
    Publication statusPublished - 2012 Jan 6

    Fingerprint

    Neuroprotective Agents
    Melatonin
    Dopamine
    Interleukin-1
    Oxidants
    Catalase
    Messenger RNA
    Putamen
    Tyrosine 3-Monooxygenase
    Mesencephalon
    Cytokines
    Free Radical Scavengers
    Enzymes
    Glutathione Peroxidase
    Weaning
    Superoxides
    Drinking Water
    Therapeutics
    Immunohistochemistry
    Neurons

    Keywords

    • Degeneration
    • Dopamine
    • Melatonin
    • Neuroprotection
    • Oxidative stress
    • PD model

    ASJC Scopus subject areas

    • Neuroscience(all)

    Cite this

    Neuroprotective effects of melatonin on the nigrostriatal dopamine system in the zitter rat. / Hashimoto, Ken ichi; Ueda, Shuichi; Ehara, Ayuka; Sakakibara, Shinichi; Yoshimoto, Kanji; Hirata, Koichi.

    In: Neuroscience Letters, Vol. 506, No. 1, 06.01.2012, p. 79-83.

    Research output: Contribution to journalArticle

    Hashimoto, Ken ichi ; Ueda, Shuichi ; Ehara, Ayuka ; Sakakibara, Shinichi ; Yoshimoto, Kanji ; Hirata, Koichi. / Neuroprotective effects of melatonin on the nigrostriatal dopamine system in the zitter rat. In: Neuroscience Letters. 2012 ; Vol. 506, No. 1. pp. 79-83.
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