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DNA Hypermethylation Induced by L-Methionine Leads to Oligodendroglial and Myelin Deficits and Schizophrenia-Like Behaviors in Adolescent Mice

Increasing evidence has demonstrated that in addition to dysfunction of neuronal circuitry, oligodendroglial dysfunction and/or disruption of white matter integrity are found in the brains of patients with schizophrenia. DNA methylation, a well-established risk factor for schizophrenia, has been dem...

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Autores principales: Chen, Xianjun, Huang, Nan-Xin, Cheng, Yong-Jie, Cai, Qi-Yan, Tian, Yan-Ping, Chen, Xing-Shu, Xiao, Lan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8095669/
https://www.ncbi.nlm.nih.gov/pubmed/33958986
http://dx.doi.org/10.3389/fnins.2021.659853
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author Chen, Xianjun
Huang, Nan-Xin
Cheng, Yong-Jie
Cai, Qi-Yan
Tian, Yan-Ping
Chen, Xing-Shu
Xiao, Lan
author_facet Chen, Xianjun
Huang, Nan-Xin
Cheng, Yong-Jie
Cai, Qi-Yan
Tian, Yan-Ping
Chen, Xing-Shu
Xiao, Lan
author_sort Chen, Xianjun
collection PubMed
description Increasing evidence has demonstrated that in addition to dysfunction of neuronal circuitry, oligodendroglial dysfunction and/or disruption of white matter integrity are found in the brains of patients with schizophrenia. DNA methylation, a well-established risk factor for schizophrenia, has been demonstrated to cause neuronal dysfunction; however, whether dysregulation of DNA methylation contributes to oligodendroglial/myelin deficits in the pathogenesis of schizophrenia remains unclear. In the present study, by using L-methionine-treated mice, we confirmed that mice with DNA hypermethylation exhibited an anxious phenotype, impaired sociability, and sensorimotor gating deficits. Notably, DNA hypermethylation in oligodendroglial cells led to dysregulation of multiple oligodendroglia-specific transcription factors, which indicated disruption of the transcriptional architecture. Furthermore, DNA hypermethylation caused a reduction of oligodendroglial lineage cells and myelin integrity in the frontal white matter of mice. Taken together, these results indicate that DNA hypermethylation leads to oligodendroglial and/or myelin deficits, which may, at least in part, contribute to schizophrenia-like behaviors in mice. This study provides new insights into the possibility that precise modulation of DNA methylation status in oligodendroglia could be beneficial for the white matter pathology in schizophrenia.
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spelling pubmed-80956692021-05-05 DNA Hypermethylation Induced by L-Methionine Leads to Oligodendroglial and Myelin Deficits and Schizophrenia-Like Behaviors in Adolescent Mice Chen, Xianjun Huang, Nan-Xin Cheng, Yong-Jie Cai, Qi-Yan Tian, Yan-Ping Chen, Xing-Shu Xiao, Lan Front Neurosci Neuroscience Increasing evidence has demonstrated that in addition to dysfunction of neuronal circuitry, oligodendroglial dysfunction and/or disruption of white matter integrity are found in the brains of patients with schizophrenia. DNA methylation, a well-established risk factor for schizophrenia, has been demonstrated to cause neuronal dysfunction; however, whether dysregulation of DNA methylation contributes to oligodendroglial/myelin deficits in the pathogenesis of schizophrenia remains unclear. In the present study, by using L-methionine-treated mice, we confirmed that mice with DNA hypermethylation exhibited an anxious phenotype, impaired sociability, and sensorimotor gating deficits. Notably, DNA hypermethylation in oligodendroglial cells led to dysregulation of multiple oligodendroglia-specific transcription factors, which indicated disruption of the transcriptional architecture. Furthermore, DNA hypermethylation caused a reduction of oligodendroglial lineage cells and myelin integrity in the frontal white matter of mice. Taken together, these results indicate that DNA hypermethylation leads to oligodendroglial and/or myelin deficits, which may, at least in part, contribute to schizophrenia-like behaviors in mice. This study provides new insights into the possibility that precise modulation of DNA methylation status in oligodendroglia could be beneficial for the white matter pathology in schizophrenia. Frontiers Media S.A. 2021-04-20 /pmc/articles/PMC8095669/ /pubmed/33958986 http://dx.doi.org/10.3389/fnins.2021.659853 Text en Copyright © 2021 Chen, Huang, Cheng, Cai, Tian, Chen and Xiao. 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 Neuroscience
Chen, Xianjun
Huang, Nan-Xin
Cheng, Yong-Jie
Cai, Qi-Yan
Tian, Yan-Ping
Chen, Xing-Shu
Xiao, Lan
DNA Hypermethylation Induced by L-Methionine Leads to Oligodendroglial and Myelin Deficits and Schizophrenia-Like Behaviors in Adolescent Mice
title DNA Hypermethylation Induced by L-Methionine Leads to Oligodendroglial and Myelin Deficits and Schizophrenia-Like Behaviors in Adolescent Mice
title_full DNA Hypermethylation Induced by L-Methionine Leads to Oligodendroglial and Myelin Deficits and Schizophrenia-Like Behaviors in Adolescent Mice
title_fullStr DNA Hypermethylation Induced by L-Methionine Leads to Oligodendroglial and Myelin Deficits and Schizophrenia-Like Behaviors in Adolescent Mice
title_full_unstemmed DNA Hypermethylation Induced by L-Methionine Leads to Oligodendroglial and Myelin Deficits and Schizophrenia-Like Behaviors in Adolescent Mice
title_short DNA Hypermethylation Induced by L-Methionine Leads to Oligodendroglial and Myelin Deficits and Schizophrenia-Like Behaviors in Adolescent Mice
title_sort dna hypermethylation induced by l-methionine leads to oligodendroglial and myelin deficits and schizophrenia-like behaviors in adolescent mice
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8095669/
https://www.ncbi.nlm.nih.gov/pubmed/33958986
http://dx.doi.org/10.3389/fnins.2021.659853
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