AUTHOR=Yang Liqin , Xia Zhixiong , Feng Jianhua , Zhang Menghuan , Miao Pu , Nie Yingjie , Zhang Xiangyan , Hao Zijian , Hu Ronggui 

TITLE=Retinoic Acid Supplementation Rescues the Social Deficits in Fmr1 Knockout Mice

JOURNAL=Frontiers in Genetics

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2022.928393

DOI=10.3389/fgene.2022.928393

ISSN=1664-8021

ABSTRACT=<p>Autism spectrum disorder (ASD) is a heritable neurodevelopmental disorder with the underlying etiology yet incompletely understood and no cure treatment. Patients of fragile X syndrome (FXS) also manifest symptoms, e.g. deficits in social behaviors, that are core traits with ASD. Several studies demonstrated that a mutual defect in retinoic acid (RA) signaling was observed in FXS and ASD. However, it is still unknown whether RA replenishment could pose a positive effect on autistic-like behaviors in FXS. Herein, we found that RA signaling was indeed down-regulated when the expression of <italic>FMR1</italic> was impaired in SH-SY5Y cells. Furthermore, RA supplementation rescued the atypical social novelty behavior, but failed to alleviate the defects in sociability behavior or hyperactivity, in <italic>Fmr1</italic> knock-out (KO) mouse model. The repetitive behavior and motor coordination appeared to be normal. The RNA sequencing results of the prefrontal cortex in <italic>Fmr1</italic> KO mice indicated that deregulated expression of <italic>Foxp2, Tnfsf10, Lepr</italic> and other neuronal genes was restored to normal after RA treatment. Gene ontology terms of metabolic processes, extracellular matrix organization and behavioral pathways were enriched. Our findings provided a potential therapeutic intervention for social novelty defects in FXS.</p>