α-Galactosylceramide modulates the brain's inflammatory microenvironment to counteract learning and memory dysfunction in Aβ_(1–42)model mice  

α-半乳糖神经酰胺(α-Galcer)调节脑内炎症微环境改善Aβ_(1–42)模型小鼠学习记忆功能的机制研究

作　　者：Guangchan Jing Jingting Kang Chao Ji 景光婵;康静婷;纪超(中国医学科学院基础医学研究所,北京协和医学院基础学院,基础医学国家级实验教学示范中心,北京100005;中国医学科学院,北京协和医院中医科,北京100730)

机构地区：[1]National Demonstration Center for Experimental Basic Medical Education(Peking Union Medical College),Institute of Basic Medical Sciences,Chinese Academy of Medical Sciences&School of Basic Medicine,Peking Union Medical College,Beijing 100005,China [2]Department of Traditional Chinese Medicine,Peking Union Medical College Hospital,Peking Union Medical College and Chinese Academy of Medical Sciences,Beijing 100730,China

出　　处：《Journal of Chinese Pharmaceutical Sciences》2024年第12期1110-1117,共8页中国药学(英文版)

基　　金：National Natural Science Foundation of China(Grant No.81100801)。

摘　　要：Alzheimer's disease(AD)is the most prevalent neurodegenerative disorder affecting the elderly.Among its pathological mechanisms,neuroinflammation triggered by amyloid-β(Aβ)aggregation is considered a key contributor.Alternatively activated(M2)macrophages and microglia have been shown to play a pivotal role in curbing neuroinflammation,thereby offering neuroprotective effects in neurodegenerative diseases.In the present study,we explored the therapeutic potential ofα-galactosylceramide(α-Galcer)in enhancing learning and memory functions in AD model mice while delving into its underlying mechanisms.Our findings demonstrated thatα-Galcer administration lowered the interferon regulatory factor(IRF)5/IRF4 ratio,leading to a higher proportion of M2 microglia and macrophages.These beneficial effects were achieved by modulating the expression of inflammation-related cytokines in the brains of AD model mice,thereby accelerating the resolution of neuroinflammation and ultimately enhancing cognitive performance.阿尔茨海默病(Alzheimer’s disease,AD)是老年人群中最常见的神经退行性疾病。β-淀粉样蛋白(amyloid-β,Aβ)聚集诱导的神经炎症被认为是AD病理机制的关键因素。据报道,选择性激活的(M2)巨噬细胞/小胶质细胞可以及时终止神经炎症,从而在神经退行性疾病中发挥神经保护作用。本研究探讨了α-Galcer对AD模型小鼠学习记忆功能的改善作用及其机制。实验结果显示α-Galcer给药后诱导干扰素调节因子(IRF)5/IRF4的比值降低,从而促进M2型小胶质细胞比例增加。α-Galcer的这些作用主要是通过影响AD模型小鼠脑内炎症相关细胞因子的表达,从而诱导神经炎症反应的适时终止,最终发挥认知功能的改善作用。

关 键 词：Alzheimer’s disease Α-GALCER M2 microglia/macrophage NEUROINFLAMMATION Microglial polarization 

分 类 号：R962.1[医药卫生—药理学]