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.