title: Neuroprotective effects of melatonin on the nigrostriatal dopamine system in the zitter rat.
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.
authors: Department of Histology and Neurobiology, Dokkyo Medical University School of Medicine, Mubu, Tochigi 321-0293, Japan.
authors: Ken-Ichi
authors: K
authors: Hashimoto
authors: Shuichi
authors: S
authors: Ueda
authors: Ayuka
authors: A
authors: Ehara
authors: Shin-Ichi
authors: S
authors: Sakakibara
authors: Kanji
authors: K
authors: Yoshimoto
authors: Koichi
authors: K
authors: Hirata
mesh_terms: D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism*; D059290:Dopaminergic Neurons / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects; D008550:Melatonin / Q000627:therapeutic use*; D008636:Mesencephalon / Q000187:drug effects / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D051381:Rats; D011922:Rats, Mutant Strains; D017207:Rats, Sprague-Dawley; D020955:Striatonigral Degeneration / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D016207:Cytokines; D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents; D015102:3,4-Dihydroxyphenylacetic Acid; D014446:Tyrosine 3-Monooxygenase; D008550:Melatonin; D004298:Dopamine