慢性酒精暴露通过激活TLR4/NF-κB通路损伤小鼠学习记忆功能  

Chronic alcohol exposure impaired learning and memory in mice by activating TLR4/NF-κB pathway

作　　者：张鑫磊[1] 王路路 崔亨贞 郑庆蒙 徐晨[1] 孟垚 乔晓孟 ZHANG Xinlei;WANG Lulu;CUI Hengzhen;ZHENG Qingmeng;XU Chen;MENG Yao;QIAO Xiaomeng(Department of Forensic Medicine,Zhengzhou University,Zhengzhou 450001,China;School of Basic Medicine,Zhengzhou University,Zhengzhou 450001,China)

机构地区：[1]郑州大学法医学系,郑州450001 [2]郑州大学基础医学院,郑州450001

出　　处：《神经解剖学杂志》2023年第1期63-70,共8页Chinese Journal of Neuroanatomy

基　　金：国家自然科学基金(82101978);河南省自然科学基金(212300410260);河南省博士后科研启动项目(202002001)。

摘　　要：目的:研究慢性酒精暴露对小鼠空间记忆的影响及其潜在的神经生物学机制。方法:建立小鼠慢性间歇性酒精暴露模型,通过Morris水迷宫检测小鼠空间记忆。采用免疫荧光染色检测小鼠海马中小胶质细胞标记物离子钙接头蛋白1(Iba-1)的激活状态和神经元突触后致密蛋白95(PSD95)的表达。运用Western Blot检测小胶质细胞膜受体toll样受体4(TLR4)及其下游分子核因子κB(NF-κB)、白细胞介素1β(IL-1β)和PSD95的表达。结果:行为学检测结果显示,慢性酒精暴露小鼠逃避潜伏期均长于对照组小鼠,同时在目标象限停留时间显著低于对照组。慢性酒精暴露组小鼠海马中Iba-1平均荧光强度显著高于对照组,TLR4、NF-κB(p65)和IL-1β蛋白表达较对照组显著升高。PSD95的蛋白表达量和平均荧光强度均较对照组低。结论:慢性间歇性酒精暴露诱导小胶质细胞大量激活,通过TLR4/NF-κB通路促进促炎因子IL-1β的表达,下调PSD95的表达,可能损害神经元功能,损害小鼠的空间记忆。Objective:To investigate the effect of chronic alcohol exposure on spatial memory in mice and its underlying neurobiological mechanism.Methods:A mouse model of chronic intermittent alcohol exposure was established,and spatial memory was detected by the Morris water maze(MWM).The activation of microglia markers ionized calcium binding adapter molecule 1(Iba-1)and expression of protein postsynaptic density 95(PSD95)in hippocampus(Hip)of mice were detected by immunofluorescence staining.Microglial cell membrane receptor toll-like receptor 4(TLR4)and its downstream molecule nuclear factor kappa-B(NF-κB),interleukin-1 beta(IL-1β)and PSD95 were detected by Western Blot.Results:Results of the behavioral test showed that the escape latency of the alcohol-exposed group was longer than that of the control group,and the percentage of time in the target quadrant was significantly lower than that of the control group.The average fluorescence intensity of Iba-1 in the Hip of the alcohol-exposed group was significantly higher than that of the control group,and the protein expression of TLR4,NF-κB and IL-1βin the alcohol-exposed group was significantly higher than that of the control group.The protein levels and average fluorescence intensity of of PSD95 were lower than those of control group.Conclusion:Chronic intermittent alcohol exposure induces massive activation of microglia and promotes the expression of proinflammatory factor IL-1βthrough the TLR4/NF-κB pathway,and down-regulates the expression of PSD95,which may impair neuronal function,thereby damaging spatial memory in mice.

关 键 词：慢性间歇性酒精暴露 空间记忆 海马 小胶质细胞 突触后致密蛋白95 小鼠 

分 类 号：R749.62[医药卫生—神经病学与精神病学]