Effects Of Alcohol Exposure On The Cognitive Function Of SAMP8 Mice And The Underlying Mechanisms

Background:Alzheimer’s disease（AD）is one of the most common degenerative diseases,with the cognitive dysfunction and behavioral decline as the main clinical manifestations.With the aggravation of the aging society,the incidence of AD is also on the rise,bringing huge economic burden to the family and the society.In addition to genetic factors,smoking,alcohol consumption,and high-salt diet as independent risk factors for AD are receiving more attention.Studies have shown that long-term alcohol exposure can cause cognitive impairment.However,the mechanism of this phenomenon remains unclear.Aims:To observe the effects of alcohol exposure on cognitive function in rapidly aging mice（SAMP8 mice）and to explore the possible mechanism.Methods:SAMP8 mice aged 3 months were randomly divided into drinking group and control group.The drinking group:drinking 20%ethanol for 3 hours a day,alcohol exposure time for 4 weeks,and feeding with double steamed water for the rest of the time;Control group:drinking double steamed water every day.Behavioral tests include open field experiment,water maze and elevated cross experiment.In addition,western blotting,morphology and enzyme-linked immunosorbent assay were also used in this study.Results:After 4 weeks of alcohol exposure,in the open field,water maze,elevated cross and other behavioral tests,the learning and memory ability of mice in the drinking group decreased.In immunofluorescence experiments,we found that the mice hippocampus neuron number does not appear obvious changes,and then using western blot of synapsin protein involved in synaptic were determined,in addition,we found that drinking mice hippocampus microtubule associated protein tau protein phosphorylation of 205 loci levels increase,but there is no obvious changes in total tau protein content.Plasma levels of Aβ_1-42 were also increased.Further investigation revealed activation of the Akt/GSK3βsignaling pathway and increased levels ofγ-secretase in the hippocampus.Conclusions:1.The learning and memory ability of SAMP8 mice was impaired under alcohol exposure;2.The number of neurons in the hippocampus of the drinking group was not significantly decreased,but the expression of synaptic related proteins was decreased.3.Activation of protein kinase GSK3βincreased the phosphorylation level of Tau protein at Thr205 in the hippocampus of mice in the drinking group;4.The expression ofγ-secretase in hippocampus and plasma Aβ1-42 were were not significantly influnenced by alcoholic exposure.Alcohol exposure can promote Tau phosphorylation to induce AD-like pathological changes in SAMP8 mice,and then damage the ability of learning and memory in mice.