膳食补充芝麻素对APP/PS1转基因小鼠认知障碍的改善作用及机制

The Preventive Effects and Mechanism of Supplementation of Sesamin on Cognitive Deficits in APP/PS1 Transgenic Mice

目的:芝麻素是我国重要油料作物芝麻中的木脂素类活性成分,具有抗氧化、抗炎、抗抑郁等多种生理功能。本文旨在研究其对阿尔兹海默症等神经退行性变化中的认知功能障碍的改善作用及潜在机制。方法:选取6月龄APP/PS1转基因小鼠进行膳食补充芝麻素(质量分数0.05%)干预3个月,利用莫里斯水迷宫实验研究小鼠认知功能的变化;通过免疫荧光及免疫组化实验检测小鼠脑部各区域IBA-1及PSD-95蛋白的表达;利用免疫印迹及qRT-PCR技术对相关基因及信号通路蛋白进行检测;结果:芝麻素有效改善了小鼠的认知功能,降低了脑内β-淀粉样蛋白(Aβ)的聚集,增加了突触相关蛋白PSD-95的表达;同时芝麻素减少了小胶质细胞标志物IBA-1的表达,抑制了脑内神经炎症的发生,减少了APP蛋白的表达并激活AKT/IDE通路。结论:芝麻素改善了APP/PS1转基因小鼠的认知功能障碍。本研究为深入探索芝麻素的神经保护作用及其应用提供了一定的理论基础。

Objective:Sesamin is a lignan food functional component from sesame seed and possess multiple bioactives,including antioxidant,anti-inflammatory and anti-depression.Here,we investigated the neuroprotective effects sesamin on preventing cognitive deficits in Alzheimer’s disease(AD)mouse model.Methods:The 6-month old female APP/PS1 transgenic mice were dietary supplemented with sesamin(0.05%,weight/weight)for 3 months.Results:It has been found that dietary supplementation of sesamin alleviated the cognitive impairment.Sesamin reduced Aβaccumulation and the expression of PSD-95 in mice brain.In addition,sesamin suppressed the microglial activation by inhibiting IBA-1 expression in hippocampus.Moreover,sesamin treatment significantly downregulated APP expression and activated the AKT/IDE signaling in the cortex.Conclusion:The results indicated that sesamin could alleviated the cognitive disorders in APP/PS1 mice.This study provides a clue for the potential beneficial neuroprotective effects for sesamin supplementation.