Melatonin regulates the aging mouse hippocampal homeostasis via the sirtuin1-foxo1 pathway

© 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,...

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Main Authors: Anorut Jenwitheesuk, Parichart Boontem, Prapimpun Wongchitrat, Jiraporn Tocharus, Sujira Mukda, Piyarat Govitrapong
Format: Journal
Published: 2018
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http://cmuir.cmu.ac.th/jspui/handle/6653943832/56543
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Institution: Chiang Mai University
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spelling th-cmuir.6653943832-565432018-09-05T03:51:53Z Melatonin regulates the aging mouse hippocampal homeostasis via the sirtuin1-foxo1 pathway Anorut Jenwitheesuk Parichart Boontem Prapimpun Wongchitrat Jiraporn Tocharus Sujira Mukda Piyarat Govitrapong Agricultural and Biological Sciences Biochemistry, Genetics and Molecular Biology Pharmacology, Toxicology and Pharmaceutics © 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. 2018-09-05T03:27:24Z 2018-09-05T03:27:24Z 2017-03-23 Journal 16112156 2-s2.0-85019683931 10.17179/excli2016-852 https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85019683931&origin=inward http://cmuir.cmu.ac.th/jspui/handle/6653943832/56543
institution Chiang Mai University
building Chiang Mai University Library
country Thailand
collection CMU Intellectual Repository
topic Agricultural and Biological Sciences
Biochemistry, Genetics and Molecular Biology
Pharmacology, Toxicology and Pharmaceutics
spellingShingle Agricultural and Biological Sciences
Biochemistry, Genetics and Molecular Biology
Pharmacology, Toxicology and Pharmaceutics
Anorut Jenwitheesuk
Parichart Boontem
Prapimpun Wongchitrat
Jiraporn Tocharus
Sujira Mukda
Piyarat Govitrapong
Melatonin regulates the aging mouse hippocampal homeostasis via the sirtuin1-foxo1 pathway
description © 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.
format Journal
author Anorut Jenwitheesuk
Parichart Boontem
Prapimpun Wongchitrat
Jiraporn Tocharus
Sujira Mukda
Piyarat Govitrapong
author_facet Anorut Jenwitheesuk
Parichart Boontem
Prapimpun Wongchitrat
Jiraporn Tocharus
Sujira Mukda
Piyarat Govitrapong
author_sort Anorut Jenwitheesuk
title Melatonin regulates the aging mouse hippocampal homeostasis via the sirtuin1-foxo1 pathway
title_short Melatonin regulates the aging mouse hippocampal homeostasis via the sirtuin1-foxo1 pathway
title_full Melatonin regulates the aging mouse hippocampal homeostasis via the sirtuin1-foxo1 pathway
title_fullStr Melatonin regulates the aging mouse hippocampal homeostasis via the sirtuin1-foxo1 pathway
title_full_unstemmed Melatonin regulates the aging mouse hippocampal homeostasis via the sirtuin1-foxo1 pathway
title_sort melatonin regulates the aging mouse hippocampal homeostasis via the sirtuin1-foxo1 pathway
publishDate 2018
url https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85019683931&origin=inward
http://cmuir.cmu.ac.th/jspui/handle/6653943832/56543
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