Melatonin ameliorates Aβ1-42-induced Alzheimer's cognitive deficits in mouse model

Abstract

Objectives The objective of this study was to evaluate whether melatonin could ameliorate cognitive function in Ab 1-42 -induced mouse model and its underlying mechanisms. Methods Series behaviour tests were performed to demonstrate the amelioration of cognitive function of the Alzheimer's disease (AD) mice induced by Ab 1-42 . Additionally, enzyme-linked immunosorbent assay was applied to detect the expression of Ab 1-42 , BACE1 and p-tau protein in the brain of the AD mice. JC-1 was performed to investigate the role in alleviating mitochondrial damage by melatonin in vitro. Western blot was used to detect the expression of melatonin on apoptosis-related factors caspase-3 and Bcl-2, as well as the expressions of GSK-3b and PP2A to further determine the mechanisms of melatonin on the expression of p-tau protein.Key findings Melatonin significantly ameliorated the cognitive function and mitochondrial damage in AD mice, reduced the expression levels of GSK-3b, caspase-3, Ab 1-42 , BACE1, p-tau protein and increased the expressions of PP2A and Bcl-2. Conclusion From the overall results, we concluded that melatonin alleviated the mitochondrial damage effectively and decreased the expressions of the p-tau and some key proteins of apoptosis, leading to the improvement of cognitive function of the mice induced by Ab 1-42 .

Effects of the drug combination memantine and melatonin on impaired memory and brain neuronal deficits in an amyloid-predominant mouse model of Alzheimer's disease

“…[23,[49][50][51] Memantine as well as melatonin has been previously associated with improvement in cognitive performance in animal models of AD. [52][53][54] In this study, melatonin given alone improved episodic memory (object recognition test) in 5xFAD mice, whereas administration of memantine did not produce a statistically significant effect. The combination of memantine + melatonin significantly enhanced memory performance in transgenic animals compared with memantine or melatonin given alone.…”

“…Memantine as well as melatonin has been previously associated with improvement in cognitive performance in animal models of AD . In this study, melatonin given alone improved episodic memory (object recognition test) in 5xFAD mice, whereas administration of memantine did not produce a statistically significant effect.…”

Melatonin induces mechanisms of brain resilience against neurodegeneration

“…Cell culture studies have unveiled that antiamyloid effects of melatonin are mediated by antioxidant mechanisms and by stimulation of the nonamyloidogenic processing of APP . Protection against oxidative stress and related mitochondrial dysfunction by chronic dosing of melatonin is well documented in several mouse models and previously shown in 3xTg‐AD mice . Melatonin did not induce changes in ADAM10 and BACE1 secretases, suggesting a lack of enzymatic modulation of APP processing in 3xTg‐AD mice after the chronic treatment.…”

“…Further studies in AD transgenic mice might help to discern whether there is a long‐term normalization of these enzymes once the amyloid pathology has ceased to exist. Melatonin‐induced decrease in p‐tau is attained through the modulation of the glycogen synthase kinase 3β or other tau kinases such as cyclin‐dependent kinase 5 . We then investigated the role of melatonin on protein degradation pathways.…”

“…Furthermore, although its effect on life extension has not been fully documented, melatonin exerts multiple protective actions against processes of cellular senescence and organismal aging . Experimental treatment with melatonin has been demonstrated to be neuroprotective in aging and AD rodent models, as its administration decreased the accumulation of Aβ and hyperphosphorylated tau (p‐tau), improved neuroplasticity and neuron survival, prevented learning and memory impairment, and ameliorated anxiety and depression‐like behavior …”