摘要
三氯生(triclosan,TCS)作为抗菌剂被广泛用于日常用品中,其潜在的神经毒性效应日益受到关注。本研究旨在探讨断奶后TCS暴露对小鼠神经社会行为的影响及其相关机制。将3周龄雄性和雌性ICR小鼠随机分为溶媒(Vehicle)组和TCS组,进行为期21 d[出生后(postnatal day,PND)21~42]的TCS(0、100 mg·kg^(-1))饮水暴露,随后进行一系列行为学测试,包括:旷场测试(OFT)和新环境抑制摄食测试(NSF)评价焦虑样行为,悬尾测试(TST)和强迫游泳测试(FST)评价抑郁样行为,社会等级测试(SDT)、社会交互测试(SIT)、垫料偏好测试(BPT)和性偏好测试(SPT)评价社会行为。进一步,通过透射电镜(transmission electron microscopy,TEM)观察小鼠海马神经元和突触的超微结构。行为学结果显示,在TST和FST中,雄性TCS组的不动时间显著高于Vehicle组;在SDT中,雄性和雌性TCS组的获胜率均下降;在SIT中,雌性TCS组的嗅探指数显著降低;TEM结果显示,与Vehicle组相比,雄性和雌性TCS组的突触间隙增宽及突触后致密物(postsynaptic density,PSD)厚度下降。这些结果表明,断奶期饮用水TCS暴露会导致小鼠海马CA1区神经元和突触结构受损,并引发一系列神经社会行为异常,包括雌雄小鼠社会等级下降、雄性抑郁样行为增加以及雌性社交互动减少。
Triclosan(TCS),an antimicrobial agent commonly used in household products,has raised concerns due to its potential neurotoxic effects.This study investigated the effects and underlying mechanisms of post-weaning TCS exposure on neurobehavioral and social behaviors in mice.Three-week-old male and female ICR mice were randomly assigned to Vehicle and TCS groups,and exposed to TCS(0,100 mg·kg^(-1))via drinking water for 21 days[postnatal day(PND)21-42],respectively.Subsequently,a series of neurobehavioral tests were performed,i ncluding the open field test(OFT)and novelty-suppressed feeding task(NSF)to assess anxiety-like behavior,the tail suspension test(TST)and forced swimming test(FST)to evaluate depression-like behavior,and the social dominance test(SDT),social interaction test(SIT),bedding preference test(BPT),and sexual preference test(SPT)to evaluate social behaviors.Transmission electron microscopy(TEM)was used to examine the ultrastructural changes of neurons and synapses in the hippocampus of mice.The behavioral results indicated that the immobility time of male TCS group was significantly higher than that of Vehicle group in both TST and FST.In the SDT,TCS exposure reduced the winning rate of both sexes.In the SIT,the social interaction index of female mice in the TCS group was significantly reduced.TEM analysis revealed that compared to the Vehicle group,the TCS group showed a widened synaptic cleft and decreased thickness of the postsynaptic density(PSD)of both sexes.These findings indicate that TCS exposure via drinking water during the post-weaning period leads to structural impairments in the neurons and synapses of the hippocampal CA1 region of mice,and precipitates a series of neurosocial behavioral abnormalities,including reduced social dominance in both sexes,increased depression-like behaviors in males,and diminished social interaction in females.
作者
郝颖
黄博雅
赵烨
杜玉茹
郭向飞
李云罗
闫姝
尹希
史海水
HAO Ying;HUANG Boya;ZHAO Ye;DU Yuru;GUO Xiangfei;LI Yunluo;YAN Shu;YIN Xi;SHI Haishui(Hebei Key Laboratory of Early Life Health Promotion(SZX202419),Hebei Medical University,Shijiazhuang 050031,China;Clinical Biobank,The First Hospital of Hebei Medical University,Shijiazhuang 050031,China;Department of Functional Region of Diagnosis,Fourth Hospital of Hebei Medical University,Shijiazhuang 050011,China;Neuroscience Research Center,Institute of Medical and Health Science,Hebei Medical University,Shijiazhuang 050017,China)
出处
《生态毒理学报》
北大核心
2025年第6期312-321,共10页
Asian Journal of Ecotoxicology
基金
国家自然科学基金面上项目(82171536)
河北省中央引导地方科技发展基金项目(246Z7746G)
河北医科大学第一医院星火项目(XH202518)。
关键词
三氯生
断奶期
社会等级
抑郁
突触可塑性
triclosan
post-weaning
social dominance
depression
synaptic plasticity
