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Please use this identifier to cite or link to this item: http://repository.li.mahidol.ac.th/dspace/handle/123456789/41604
Title: Melatonin regulates the aging mouse hippocampal homeostasis via the sirtuin1-foxo1 pathway
Authors: Anorut Jenwitheesuk
Parichart Boontem
Prapimpun Wongchitrat
Jiraporn Tocharus
Sujira Mukda
Piyarat Govitrapong
Mahidol University
Chulabhorn Royal Academy
Chiang Mai University
Keywords: Agricultural and Biological Sciences;Biochemistry, Genetics and Molecular Biology
Issue Date: 23-Mar-2017
Citation: EXCLI Journal. Vol.16, (2017), 340-353
Abstract: © 2017, Leibniz Research Centre for Working Environment and Human Factors. All rights reserved. Sirtuin1 (SIRT1) and forkhead box transcription factor O subfamily 1 (FOXO1) play vital roles in the maintenance of hippocampal neuronal homeostasis during aging. Our previous study showed that melatonin, a hormone mainly secreted by the pineal gland, restored the impaired memory of aged mice. Age-related neuronal energy deficits contribute to the pathogenesis of several neurodegenerative disorders. An attempt has been made to determine whether the effect of melatonin is mediated through the SIRT1-FOXO1 pathways. The present results showed that aged mice (22 months old) exhibited significantly downregulated SIRT1, FOXO1, and melatonin receptors MT1 and MT2 protein expression but upregulated tumor suppressor protein 53 (p53), acetyl-p53 protein (Ac-p53), mouse double minute 2 homolog (MDM2), Dickkopf-1 (DKK1) protein expression in mouse hippocampus compared with the young group. Melatonin treatment (10 mg/kg, daily in drinking water for 6 months) in aged mice significantly attenuated the age-induced downregulation of SIRT1, FOXO1, MT1 and MT2 protein expression and attenuated the age-induced increase in p53, ac-p53, MDM2, and DKK1 protein and mRNA expression. Melatonin decreased p53 and MDM2 expression, which led to a decrease in FOXO1 degradation. These present results suggest that melatonin may help the hippocampal neuronal homeostasis by increasing SIRT1, FOXO1 and melatonin receptors expression while decreasing DKK1 expression in the aging hippocampus. DKK1 can be induced by the accumulation of amyloid β (Aβ) which is the major hallmark of Alzheimer’s disease.
URI: https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85019683931&origin=inward
http://repository.li.mahidol.ac.th/dspace/handle/123456789/41604
ISSN: 16112156
Appears in Collections:Scopus 2016-2017

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