Melatonin regulates the aging mouse hippocampal homeostasis via the sirtuin1-FOXO1 pathway

Authors

  • Anorut Jenwitheesuk Research Center for Neuroscience, Institute of Molecular Biosciences, Mahidol University, Salaya, Nakornpathom, Thailand
  • Parichart Boontem Chulabhorn Graduate Institute, Chulabhorn Royal Academy, Bangkok 10210, Thailand
  • Prapimpun Wongchitrat Center for Research and Innovation, Faculty of Medical Technology, Mahidol University, Salaya, Nakon Pathom 73170, Thailand
  • Jiraporn Tocharus Department of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand
  • Sujira Mukda Research Center for Neuroscience, Institute of Molecular Biosciences, Mahidol University, Salaya, Nakornpathom, Thailand
  • Piyarat Govitrapong Research Center for Neuroscience, Institute of Molecular Biosciences, Mahidol University, Salaya, Nakornpathom, Thailand; Chulabhorn Graduate Institute, Chulabhorn Royal Academy, Bangkok 10210, Thailand; Center for Neuroscience and Department of Pharmacology, Faculty of Science, Mahidol University, Bangkok, Thailand

DOI:

https://doi.org/10.17179/excli2016-852

Keywords:

melatonin, aging, hippocampus, sirtuin1, FOXO1, melatonin receptor

Abstract

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.

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Published

2017-03-23

How to Cite

Jenwitheesuk, A., Boontem, P., Wongchitrat, P., Tocharus, J., Mukda, S., & Govitrapong, P. (2017). Melatonin regulates the aging mouse hippocampal homeostasis via the sirtuin1-FOXO1 pathway. EXCLI Journal, 16, 340–353. https://doi.org/10.17179/excli2016-852

Issue

Vol. 16 (2017)

Section

Original articles

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