Retinoic acid supplementation ameliorates motor incoordination via RAR alpha-CBLN2 in the cerebellum of a prenatal valproic acid-exposed rat autism model

作者全名："Yuan, Binlin; Luo, Lijuan; Hu, Chaoqun; Lin, Fang; Yang, Ting; Chen, Jie; Li, Tingyu"

作者地址："[Yuan, Binlin; Luo, Lijuan; Hu, Chaoqun; Lin, Fang; Yang, Ting; Chen, Jie; Li, Tingyu] Chongqing Med Univ, Childrens Nutr Res Ctr, Chongqing Key Lab Childhood Nutr & Hlth, Minist Educ,Natl Clin Res Ctr Child Hlth & Disorde, Chongqing, Peoples R China"

通信作者："Chen, J; Li, TY (通讯作者)，Chongqing Med Univ, Childrens Nutr Res Ctr, Chongqing Key Lab Childhood Nutr & Hlth, Minist Educ,Natl Clin Res Ctr Child Hlth & Disorde, Chongqing, Peoples R China."

来源：NEUROSCIENCE LETTERS

ESI学科分类：NEUROSCIENCE & BEHAVIOR

WOS号：WOS:001010967500001

JCR分区：Q3

影响因子：2.5

年份：2023

卷号：809

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：Autism spectrum disorder; Motor incoordination; Retinoic acid; Cerebellum

摘要："In addition to their core symptoms, most individuals with autism spectrum disorder (ASD) also experience motor impairments. These impairments are often linked to the cerebellum, which is the focus of the current study. Herein, we utilized a prenatal valproic acid (VPA)-induced rat model of autism and performed RNA sequencing in the cerebellum. Relative to control animals, the VPA-treated offspring demonstrated both abnormal motor coordination and impaired dendritic arborization of Purkinje cells (PCs). Concurrently, we observed a decrease in the cerebellar expression of retinoic acid (RA) synthesis enzymes (RDH10, ALDH1A1), metabolic enzyme (CYP26A2), and lower levels of RA, retinoic acid receptor alpha (RAR alpha), and Cerebellin2 (CBLN2) in the VPA-treated offspring. However, RA supplementation ameliorated these deficits, restoring motor coordination, normalizing PCs dendritic arborization, and increasing the expression of RA, RAR alpha, and CBLN2. Further, ChIP assays confirmed that RA supplementation enhanced RAR alpha's binding capacity to CBLN2 promoters. Collectively, these findings highlight the therapeutic potential of RA for treating motor incoordination in VPA-induced autism, acting through the RAR alpha-CBLN2 pathway."

基金机构："National Natural Science Foundation of China [81771223, 81770526, 31971089]; Chief Medical Expert Studio of Chongqing [YWBF [2018] 263]"

基金资助正文："This work received financial support from the National Natural Science Foundation of China (Grants Nos. 81771223, 81770526, 31971089) and the Chief Medical Expert Studio of Chongqing (Grant No. YWBF [2018] 263) ."