Retinoic acid administration normalizes aberrant microglial activation via regulating TREM2 transcription in the PFC of valproic acid induced autism rat

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

作者地址："[Luo, Lijuan; Li, Tingyu; Wu, Qionghui; Yuan, Binlin; Hu, Chaoqun; Yang, Ting; Wei, Hua; Chen, Jie] Childrens Hosp Chongqing Med Univ, Childrens Nutr Res Ctr, Natl Clin Res Ctr Child Hlth & Disorders, Chongqing Key Lab Child Nutr & Hlth,Minist Educ Ke, Chongqing, Peoples R China; [Li, Tingyu; Wei, Hua] Childrens Hosp Chongqing Med Univ, Dept Child Hlth Care, Chongqing, Peoples R China; [Wei, Hua; Chen, Jie] Childrens Hosp Chongqing Med Univ, Childrens Nutr Res Ctr, Chongqing 400014, Peoples R China"

通信作者："Wei, H; Chen, J (通讯作者)，Childrens Hosp Chongqing Med Univ, Childrens Nutr Res Ctr, Chongqing 400014, Peoples R China."

来源：NEUROSCIENCE LETTERS

ESI学科分类：NEUROSCIENCE & BEHAVIOR

WOS号：WOS:000957239800001

JCR分区：Q3

影响因子：2.5

年份：2023

卷号：803

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：Autism spectrum disorder; Retinoic acid; Retinoic acid receptor ?; Microglial activation; Triggering receptor expressed on myeloid cells

摘要："Autism spectrum disorder (ASD) is a complex neurodevelopmental disease with an unclear underlying patho-genesis. Disruption of retinoic acid (RA)-retinoic acid receptor alpha (RAR alpha) signaling and aberrant microglial activation were reported to be involved in the pathogenesis of ASD. However, the effect of RA-RAR alpha signaling on microglial activation in ASD and the underlying mechanisms are unknown. Herein, we found inhibited RA-RAR alpha signaling and increased microglial activation in valproic acid (VPA)-induced autism rats. Furthermore, we administered RA to VPA rats and found that RA ameliorated autism-like behaviors, inhibited microglial acti-vation and normalized microglial polarization in VPA rats. Additionally, the expression levels of RAR alpha and triggering receptor expressed on myeloid cells 2 (TREM2) were increased in the prefrontal cortex (PFC) of VPA rats given RA. Chromatin immunoprecipitation (ChIP) and dual luciferase reporter assays confirmed that RAR alpha can regulate the transcriptional activity of the TREM2 gene by binding to its promoter. We conclude that RA administration ameliorates autism-like behaviors in VPA rats by inhibiting microglial activation and normalizing microglial polarization through the regulation of TREM2 transcription by RAR alpha."

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) ."