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

EXCLI Journal
Anorut JenwitheesukPiyarat Govitrapong

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 i...Continue Reading

Citations

Dec 2, 2017·The Journal of Experimental Medicine·Mark Y JengMelanie Ott
Dec 19, 2018·Frontiers in Pharmacology·Peter PetschnerGyorgy Bagdy

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Methods Mentioned

BETA
ubiquitination
reverse transcription PCR
PCR
protein assay
acetylation
nuclear translocation

Software Mentioned

GraphPad Prism
Gene Tools
Scion image

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