Altered expression of glycan patterns and glycan-related genes in the medial prefrontal cortex of the valproic acid rat model of autism

Autism spectrum disorders (ASD) represent a group of neurodevelopmental defects characterized by social deficits and repetitive behaviors. Alteration in Glycosylation patterns could influence the nervous system development and contribute to the molecular mechanism of ASD. Interaction of environmenta...

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Main Authors: Yingxun Liu, Yuanyuan Di, Qi Zheng, Zhaoqiang Qian, Juan Fan, Wei Ren, Zhaoming Wei, Yingfang Tian
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-12-01
Series:Frontiers in Cellular Neuroscience
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fncel.2022.1057857/full
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author Yingxun Liu
Yingxun Liu
Yingxun Liu
Yuanyuan Di
Qi Zheng
Zhaoqiang Qian
Juan Fan
Juan Fan
Wei Ren
Zhaoming Wei
Zhaoming Wei
Yingfang Tian
Yingfang Tian
author_facet Yingxun Liu
Yingxun Liu
Yingxun Liu
Yuanyuan Di
Qi Zheng
Zhaoqiang Qian
Juan Fan
Juan Fan
Wei Ren
Zhaoming Wei
Zhaoming Wei
Yingfang Tian
Yingfang Tian
author_sort Yingxun Liu
collection DOAJ
description Autism spectrum disorders (ASD) represent a group of neurodevelopmental defects characterized by social deficits and repetitive behaviors. Alteration in Glycosylation patterns could influence the nervous system development and contribute to the molecular mechanism of ASD. Interaction of environmental factors with susceptible genes may affect expressions of glycosylation-related genes and thus result in abnormal glycosylation patterns. Here, we used an environmental factor-induced model of autism by a single intraperitoneal injection of 400 mg/kg valproic acid (VPA) to female rats at day 12.5 post-conception. Following confirmation of reduced sociability and increased self-grooming behaviors in VPA-treated offspring, we analyzed the alterations in the expression profile of glycan patterns and glycan-related genes by lectin microarrays and RNA-seq, respectively. Lectin microarrays detected 14 significantly regulated lectins in VPA rats, with an up-regulation of high-mannose with antennary and down-regulation of Siaα2-3 Gal/GalNAc. Based on the KEGG and CAZy resources, we assembled a comprehensive list of 961 glycan-related genes to focus our analysis on specific genes. Of those, transcription results revealed that there were 107 differentially expressed glycan-related genes (DEGGs) after VPA treatment. Functional analysis of DEGGs encoding anabolic enzymes revealed that the process trimming to form core structure and glycan extension from core structure primarily changed, which is consistent with the changes in glycan patterns. In addition, the DEGGs encoding glycoconjugates were mainly related to extracellular matrix and axon guidance. This study provides insights into the underlying molecular mechanism of aberrant glycosylation after prenatal VPA exposure, which may serve as potential biomarkers for the autism diagnosis.
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spelling doaj.art-3cb22dea4bac4cbba6a7a33220706c152022-12-22T03:49:25ZengFrontiers Media S.A.Frontiers in Cellular Neuroscience1662-51022022-12-011610.3389/fncel.2022.10578571057857Altered expression of glycan patterns and glycan-related genes in the medial prefrontal cortex of the valproic acid rat model of autismYingxun Liu0Yingxun Liu1Yingxun Liu2Yuanyuan Di3Qi Zheng4Zhaoqiang Qian5Juan Fan6Juan Fan7Wei Ren8Zhaoming Wei9Zhaoming Wei10Yingfang Tian11Yingfang Tian12Key Laboratory of Ministry of Education for Medicinal Plant Resource and Natural Pharmaceutical Chemistry, National Engineering Laboratory for Resource Developing of Endangered Chinese Crude Drugs in Northwest of China, College of Life Sciences, Shaanxi Normal University, Xi’an, Shaanxi, ChinaCollege of Life Sciences, Shaanxi Normal University, Xi’an, Shaanxi, ChinaGenetic Engineering Laboratory, College of Biological and Environmental Engineering, Xi’an University, Xi’an, Shaanxi, ChinaCollege of Life Sciences, Shaanxi Normal University, Xi’an, Shaanxi, ChinaCollege of Life Sciences, Shaanxi Normal University, Xi’an, Shaanxi, ChinaCollege of Life Sciences, Shaanxi Normal University, Xi’an, Shaanxi, ChinaKey Laboratory of Ministry of Education for Medicinal Plant Resource and Natural Pharmaceutical Chemistry, National Engineering Laboratory for Resource Developing of Endangered Chinese Crude Drugs in Northwest of China, College of Life Sciences, Shaanxi Normal University, Xi’an, Shaanxi, ChinaCollege of Life Sciences, Shaanxi Normal University, Xi’an, Shaanxi, ChinaSchool of Education, Shaanxi Normal University, Xi’an, Shaanxi, ChinaKey Laboratory of Ministry of Education for Medicinal Plant Resource and Natural Pharmaceutical Chemistry, National Engineering Laboratory for Resource Developing of Endangered Chinese Crude Drugs in Northwest of China, College of Life Sciences, Shaanxi Normal University, Xi’an, Shaanxi, ChinaCollege of Life Sciences, Shaanxi Normal University, Xi’an, Shaanxi, ChinaKey Laboratory of Ministry of Education for Medicinal Plant Resource and Natural Pharmaceutical Chemistry, National Engineering Laboratory for Resource Developing of Endangered Chinese Crude Drugs in Northwest of China, College of Life Sciences, Shaanxi Normal University, Xi’an, Shaanxi, ChinaCollege of Life Sciences, Shaanxi Normal University, Xi’an, Shaanxi, ChinaAutism spectrum disorders (ASD) represent a group of neurodevelopmental defects characterized by social deficits and repetitive behaviors. Alteration in Glycosylation patterns could influence the nervous system development and contribute to the molecular mechanism of ASD. Interaction of environmental factors with susceptible genes may affect expressions of glycosylation-related genes and thus result in abnormal glycosylation patterns. Here, we used an environmental factor-induced model of autism by a single intraperitoneal injection of 400 mg/kg valproic acid (VPA) to female rats at day 12.5 post-conception. Following confirmation of reduced sociability and increased self-grooming behaviors in VPA-treated offspring, we analyzed the alterations in the expression profile of glycan patterns and glycan-related genes by lectin microarrays and RNA-seq, respectively. Lectin microarrays detected 14 significantly regulated lectins in VPA rats, with an up-regulation of high-mannose with antennary and down-regulation of Siaα2-3 Gal/GalNAc. Based on the KEGG and CAZy resources, we assembled a comprehensive list of 961 glycan-related genes to focus our analysis on specific genes. Of those, transcription results revealed that there were 107 differentially expressed glycan-related genes (DEGGs) after VPA treatment. Functional analysis of DEGGs encoding anabolic enzymes revealed that the process trimming to form core structure and glycan extension from core structure primarily changed, which is consistent with the changes in glycan patterns. In addition, the DEGGs encoding glycoconjugates were mainly related to extracellular matrix and axon guidance. This study provides insights into the underlying molecular mechanism of aberrant glycosylation after prenatal VPA exposure, which may serve as potential biomarkers for the autism diagnosis.https://www.frontiersin.org/articles/10.3389/fncel.2022.1057857/fullglycan-related genesglycan patternsvalproic acidautismmPFC
spellingShingle Yingxun Liu
Yingxun Liu
Yingxun Liu
Yuanyuan Di
Qi Zheng
Zhaoqiang Qian
Juan Fan
Juan Fan
Wei Ren
Zhaoming Wei
Zhaoming Wei
Yingfang Tian
Yingfang Tian
Altered expression of glycan patterns and glycan-related genes in the medial prefrontal cortex of the valproic acid rat model of autism
Frontiers in Cellular Neuroscience
glycan-related genes
glycan patterns
valproic acid
autism
mPFC
title Altered expression of glycan patterns and glycan-related genes in the medial prefrontal cortex of the valproic acid rat model of autism
title_full Altered expression of glycan patterns and glycan-related genes in the medial prefrontal cortex of the valproic acid rat model of autism
title_fullStr Altered expression of glycan patterns and glycan-related genes in the medial prefrontal cortex of the valproic acid rat model of autism
title_full_unstemmed Altered expression of glycan patterns and glycan-related genes in the medial prefrontal cortex of the valproic acid rat model of autism
title_short Altered expression of glycan patterns and glycan-related genes in the medial prefrontal cortex of the valproic acid rat model of autism
title_sort altered expression of glycan patterns and glycan related genes in the medial prefrontal cortex of the valproic acid rat model of autism
topic glycan-related genes
glycan patterns
valproic acid
autism
mPFC
url https://www.frontiersin.org/articles/10.3389/fncel.2022.1057857/full
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