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Retinoic Acid Supplementation Rescues the Social Deficits in Fmr1 Knockout Mice
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 dem...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2022
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9247356/ https://www.ncbi.nlm.nih.gov/pubmed/35783275 http://dx.doi.org/10.3389/fgene.2022.928393 |
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author | Yang, Liqin Xia, Zhixiong Feng, Jianhua Zhang, Menghuan Miao, Pu Nie, Yingjie Zhang, Xiangyan Hao, Zijian Hu, Ronggui |
author_facet | Yang, Liqin Xia, Zhixiong Feng, Jianhua Zhang, Menghuan Miao, Pu Nie, Yingjie Zhang, Xiangyan Hao, Zijian Hu, Ronggui |
author_sort | Yang, Liqin |
collection | PubMed |
description | 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 FMR1 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 Fmr1 knock-out (KO) mouse model. The repetitive behavior and motor coordination appeared to be normal. The RNA sequencing results of the prefrontal cortex in Fmr1 KO mice indicated that deregulated expression of Foxp2, Tnfsf10, Lepr 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. |
format | Online Article Text |
id | pubmed-9247356 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-92473562022-07-02 Retinoic Acid Supplementation Rescues the Social Deficits in Fmr1 Knockout Mice Yang, Liqin Xia, Zhixiong Feng, Jianhua Zhang, Menghuan Miao, Pu Nie, Yingjie Zhang, Xiangyan Hao, Zijian Hu, Ronggui Front Genet Genetics 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 FMR1 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 Fmr1 knock-out (KO) mouse model. The repetitive behavior and motor coordination appeared to be normal. The RNA sequencing results of the prefrontal cortex in Fmr1 KO mice indicated that deregulated expression of Foxp2, Tnfsf10, Lepr 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. Frontiers Media S.A. 2022-06-17 /pmc/articles/PMC9247356/ /pubmed/35783275 http://dx.doi.org/10.3389/fgene.2022.928393 Text en Copyright © 2022 Yang, Xia, Feng, Zhang, Miao, Nie, Zhang, Hao and Hu. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Genetics Yang, Liqin Xia, Zhixiong Feng, Jianhua Zhang, Menghuan Miao, Pu Nie, Yingjie Zhang, Xiangyan Hao, Zijian Hu, Ronggui Retinoic Acid Supplementation Rescues the Social Deficits in Fmr1 Knockout Mice |
title | Retinoic Acid Supplementation Rescues the Social Deficits in Fmr1 Knockout Mice |
title_full | Retinoic Acid Supplementation Rescues the Social Deficits in Fmr1 Knockout Mice |
title_fullStr | Retinoic Acid Supplementation Rescues the Social Deficits in Fmr1 Knockout Mice |
title_full_unstemmed | Retinoic Acid Supplementation Rescues the Social Deficits in Fmr1 Knockout Mice |
title_short | Retinoic Acid Supplementation Rescues the Social Deficits in Fmr1 Knockout Mice |
title_sort | retinoic acid supplementation rescues the social deficits in fmr1 knockout mice |
topic | Genetics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9247356/ https://www.ncbi.nlm.nih.gov/pubmed/35783275 http://dx.doi.org/10.3389/fgene.2022.928393 |
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