中国病理生理杂志2024，Vol.40Issue(12)：2254-2261,8.DOI:10.3969/j.issn.1000-4718.2024.12.008
小鼠青春期香烟暴露通过前额叶小胶质细胞介导的炎症反应影响成年后学习记忆功能
Smoke exposure during adolescence affects learning and memory abili-ties of mice in adulthood via prefrontal microglia-mediated inflammation
摘要
Abstract
AIM:To investigate the effects of cigarette smoke exposure during adolescence on the inflammato-ry response mediated by microglia in the prefrontal cortex of mice,and its impact on learning and memory functions in adulthood.METHODS:72 two-week-old healthy male Kunming mice,with each weighing(11.0±1.5)g,were random-ly divided into control and cigarette exposure groups(n=36 per group).The mice in the cigarette exposure group were pas-sively exposed to 6 cigarettes daily for 10 weeks.At three time points of 4-week-old(infancy),8-week-old(adoles-cence),and 12-week-old(adulthood),six mice were selected from each group to have their neurobehavioral and patholog-ical changes examined.In particular,the step-down test,three-chamber social interaction test,and novel object recogni-tion test were used to detect changes in learning and memory abilities and cognitive behavior.Immunofluorescence testing was performed to detect the morphology,number of synapses,and expression of inflammatory factor apoptosis-associated speck-like protein containing a CARD(ASC)around the microglial cells in the prefrontal cortex of mice in each group.Western blot was performed to assess the expression levels of synaptophysin(SYP)and postsynaptic density protein-95(PSD-95)in the cerebral cortex of mice in each group.Enzyme-linked immunosorbent assay(ELISA)was performed to detect the protein expression of tumor necrosis factor-α(TNF-α),interleukin 1β(IL-1β),and IL-6 in the prefrontal cor-tex.RESULTS:(1)In the step-down test,the latency of mice at 8 and 12 weeks of age was significantly shortened,and the number of errors was significantly increased in the cigarette exposure group compared with the age-matched control group(P＜0.01).In addition,the social recognition time and exploration time for novel objects were prolonged(P＜0.05).(2)Immunofluorescence assays revealed that exposure to cigarette smoke in mice,at both 8 and 12 weeks of age,resulted in a reduction of SYP-positive puncta within the prefrontal cortex.Concurrently,there was an observed increase in the number of Iba1-positive microglia,which exhibited an activated phenotype,as well as an elevation in ASC-positive puncta in proximity to the microglia.Western blot further revealed reduced expression of synaptophysin protein SYP and PSD-95 in the cerebral cortex of the mice at 8 and 12 weeks of age in the cigarette exposure group(P＜0.05).(3)ELISA showed increased levels of inflammatory factors TNF-α,IL-1β,and IL-6 in the prefrontal cortex of the mice at 8 and 12 weeks of age in the cigarette exposure group(P＜0.05).CONCLUSION:Exposure to cigarette smoke during adoles-cence in mice may result in the enhanced secretion of inflammatory factors through the activation of microglia in the pre-frontal cortex.This activation can alter microglial function and induce synaptic damage,consequently impairing learning,memory,and cognitive abilities in adulthood.关键词
香烟暴露/前额叶皮质/小胶质细胞/认知/炎症Key words
cigarette exposure/prefrontal cortex/microglia/cognition/inflammation分类
医药卫生引用本文复制引用
范文娟,陈彦锋,段子朋,孙缦利,陈旭东..小鼠青春期香烟暴露通过前额叶小胶质细胞介导的炎症反应影响成年后学习记忆功能[J].中国病理生理杂志,2024,40(12):2254-2261,8.基金项目
河南省自然科学基金资助项目(No.222300420246) （No.222300420246）
河南省重点研发与推广专项(No.232102310501) （No.232102310501）
漯河医专科技创新项目(No.2023ZD08 （）
No.2023ZD04) （）
