Prenatally VPA exposure is likely to cause autistic-like behavior in the rats offspring via TREM2 down-regulation to affect the microglial activation and synapse alterations

作者全名："Luo, Lijuan; Chen, Jie; Wu, Qionghui; Yuan, Binlin; Hu, Chaoqun; Yang, Ting; Wei, Hua; Li, Tingyu"

作者地址："[Luo, Lijuan; Chen, Jie; Wu, Qionghui; Yuan, Binlin; Hu, Chaoqun; Yang, Ting; Wei, Hua; Li, Tingyu] Chongqing Med Univ, Natl Clin Res Ctr Child Hlth & Disorders, Chongqing Key Lab Child Nutr & Hlth, Key Lab Child Dev & Disorders,Childrens Nutr Res C, Chongqing, Peoples R China; [Wei, Hua; Li, Tingyu] Chongqing Med Univ, Dept Child Hlth Care, Childrens Hosp, Chongqing, Peoples R China"

通信作者："Wei, H; Li, TY (通讯作者)，Chongqing Med Univ, Natl Clin Res Ctr Child Hlth & Disorders, Chongqing Key Lab Child Nutr & Hlth, Key Lab Child Dev & Disorders,Childrens Nutr Res C, Chongqing, Peoples R China."

来源：ENVIRONMENTAL TOXICOLOGY AND PHARMACOLOGY

ESI学科分类：PHARMACOLOGY & TOXICOLOGY

WOS号：WOS:000951815800001

JCR分区：Q1

影响因子：4.2

年份：2023

卷号：99

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：Autism spectrum disorders; Microglial activation; Microglial polarization; Synaptic pruning; Triggering receptor expressed on myeloid cells 2; Valproic acid

摘要："Microglial dysfunction has been reported in the valproic acid (VPA)-induced autism spectrum disorder (ASD) rat models. However, how does prenatal VPA exposure affect microglia remains to be elucidated. The triggering receptor expressed on myeloid cells 2 (TREM2) is revealed to be implicated in a range of microglia functions. However, reports on the association between TREM2 and VPA-induced ASD rat models are scarce. Our results showed that prenatal VPA exposure induced autistic-like behaviors, downregulated the levels of TREM2, upregulated microglial activation, dysregulated microglial polarization, and altered synapse in offspring. TREM2 overexpression partly ameliorated microglia dysfunction and autistic-like behaviors in prenatal VPA-exposed rats. Our findings demonstrated that prenatally VPA exposure is likely to cause autistic-like behavior in the rat offspring via TREM2 down-regulation to affect the microglial activation, microglial polarization and synaptic pruning of microglia for the first time."

基金机构："National Natural Science Foundation of China [82002399, 81771223, 31971089]"

基金资助正文："Funding This work was supported by the National Natural Science Foundation of China (82002399, 81771223, 31971089) ."