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Article: Poly(I:C) challenge alters brain expression of oligodendroglia-related genes of adult progeny in a mouse model of maternal immune activation

TitlePoly(I:C) challenge alters brain expression of oligodendroglia-related genes of adult progeny in a mouse model of maternal immune activation
Authors
Keywordsmaternal immune activation (MIA)
poly(I:C)
SOX10
myelin-associated glycoprotein (MAG)
transferrin (Tf)
Issue Date2020
PublisherFrontiers Research Foundation. The Journal's web site is located at http://www.frontiersin.org/molecular_neuroscience/
Citation
Frontiers in Molecular Neuroscience, 2020, v. 13, p. article no. 115 How to Cite?
AbstractBackground: Altered white matter connectivity, as evidenced by pervasive microstructural changes in myelination and axonal integrity in neuroimaging studies, has been implicated in the development of autism spectrum disorder (ASD) and related neurodevelopmental conditions such as schizophrenia. Despite an increasing appreciation that such white matter disconnectivity is linked to social behavior deficits, virtually no etiologically meaningful myelin-related genes have been identified in oligodendrocytes, the key myelinating cells in the CNS, to furnish an account on the causes. The impact of neurodevelopmental perturbations during pregnancy such as maternal immune activation (MIA) on these genes in memory-related neural networks has not been experimentally scrutinized. Methods: In this study, a mouse model of MIA by the viral dsRNA analog poly(I:C) was employed to mimic the effects of inflammation during pregnancy. Transcriptional expression levels of selected myelin- or oligodendroglia-related genes implicated in schizophrenia or ASD development were analyzed by in situ hybridization (ISH) and quantitative real-time PCR (qRT-PCR) with brain samples from MIA and control groups. The analysis focused on SOX-10 (SRY-related HMG-box 10), MAG (myelin-associated glycoprotein), and Tf (transferrin) expression in the hippocampus and the surrounding memory-related cortical regions in either hemisphere. Results: Specifically, ISH reveals that in the brain of prenatal poly(I:C)-exposed mouse offspring in the MIA model (gestation day 9), mRNA expression of the genes SOX10, MAG and Tf were generally reduced in the limbic system including the hippocampus, retrosplenial cortex and parahippocampal gyrus on either side of the hemispheres. qRT-PCR further confirms the reduction of SOX10, MAG, and Tf expression in the medial prefrontal cortex, sensory cortex, amygdala, and hippocampus. Conclusions: Our present results provide direct evidence that prenatal exposure to poly(I:C) elicits profound and long-term changes in transcript level and spatial distribution of myelin-related genes in multiple neocortical and limbic regions, notably the hippocampus and its surrounding memory-related neural networks. Our work demonstrates the potential utility of oligodendroglia-related genes as biomarkers for modeling neurodevelopmental disorders, in agreement with the hypothesis that MIA during pregnancy could lead to compromised white matter connectivity in ASD.
Persistent Identifierhttp://hdl.handle.net/10722/288310
ISSN
2023 Impact Factor: 3.5
2023 SCImago Journal Rankings: 1.223
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorZHANG, XF-
dc.contributor.authorChen, T-
dc.contributor.authorYan, A-
dc.contributor.authorXiao, J-
dc.contributor.authorXie, YL-
dc.contributor.authorYuan, J-
dc.contributor.authorChen, P-
dc.contributor.authorWong, AOL-
dc.contributor.authorZHANG, Y-
dc.contributor.authorWong, NK-
dc.date.accessioned2020-10-05T12:10:58Z-
dc.date.available2020-10-05T12:10:58Z-
dc.date.issued2020-
dc.identifier.citationFrontiers in Molecular Neuroscience, 2020, v. 13, p. article no. 115-
dc.identifier.issn1662-5099-
dc.identifier.urihttp://hdl.handle.net/10722/288310-
dc.description.abstractBackground: Altered white matter connectivity, as evidenced by pervasive microstructural changes in myelination and axonal integrity in neuroimaging studies, has been implicated in the development of autism spectrum disorder (ASD) and related neurodevelopmental conditions such as schizophrenia. Despite an increasing appreciation that such white matter disconnectivity is linked to social behavior deficits, virtually no etiologically meaningful myelin-related genes have been identified in oligodendrocytes, the key myelinating cells in the CNS, to furnish an account on the causes. The impact of neurodevelopmental perturbations during pregnancy such as maternal immune activation (MIA) on these genes in memory-related neural networks has not been experimentally scrutinized. Methods: In this study, a mouse model of MIA by the viral dsRNA analog poly(I:C) was employed to mimic the effects of inflammation during pregnancy. Transcriptional expression levels of selected myelin- or oligodendroglia-related genes implicated in schizophrenia or ASD development were analyzed by in situ hybridization (ISH) and quantitative real-time PCR (qRT-PCR) with brain samples from MIA and control groups. The analysis focused on SOX-10 (SRY-related HMG-box 10), MAG (myelin-associated glycoprotein), and Tf (transferrin) expression in the hippocampus and the surrounding memory-related cortical regions in either hemisphere. Results: Specifically, ISH reveals that in the brain of prenatal poly(I:C)-exposed mouse offspring in the MIA model (gestation day 9), mRNA expression of the genes SOX10, MAG and Tf were generally reduced in the limbic system including the hippocampus, retrosplenial cortex and parahippocampal gyrus on either side of the hemispheres. qRT-PCR further confirms the reduction of SOX10, MAG, and Tf expression in the medial prefrontal cortex, sensory cortex, amygdala, and hippocampus. Conclusions: Our present results provide direct evidence that prenatal exposure to poly(I:C) elicits profound and long-term changes in transcript level and spatial distribution of myelin-related genes in multiple neocortical and limbic regions, notably the hippocampus and its surrounding memory-related neural networks. Our work demonstrates the potential utility of oligodendroglia-related genes as biomarkers for modeling neurodevelopmental disorders, in agreement with the hypothesis that MIA during pregnancy could lead to compromised white matter connectivity in ASD.-
dc.languageeng-
dc.publisherFrontiers Research Foundation. The Journal's web site is located at http://www.frontiersin.org/molecular_neuroscience/-
dc.relation.ispartofFrontiers in Molecular Neuroscience-
dc.rightsThis Document is Protected by copyright and was first published by Frontiers. All rights reserved. It is reproduced with permission.-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subjectmaternal immune activation (MIA)-
dc.subjectpoly(I:C)-
dc.subjectSOX10-
dc.subjectmyelin-associated glycoprotein (MAG)-
dc.subjecttransferrin (Tf)-
dc.titlePoly(I:C) challenge alters brain expression of oligodendroglia-related genes of adult progeny in a mouse model of maternal immune activation-
dc.typeArticle-
dc.identifier.emailYan, A: ayan8@hku.hk-
dc.identifier.emailWong, AOL: olwong@hku.hk-
dc.identifier.authorityYan, A=rp00823-
dc.identifier.authorityWong, AOL=rp00806-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.3389/fnmol.2020.00115-
dc.identifier.pmid32714147-
dc.identifier.pmcidPMC7340146-
dc.identifier.scopuseid_2-s2.0-85087927532-
dc.identifier.hkuros314875-
dc.identifier.volume13-
dc.identifier.spagearticle no. 115-
dc.identifier.epagearticle no. 115-
dc.identifier.isiWOS:000553136300001-
dc.publisher.placeSwitzerland-
dc.identifier.issnl1662-5099-

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