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AD7c-NTP Impairs Adult Striatal Neurogenesis by Affecting the Biological Function of MeCP2 in APP/PSl Transgenic Mouse Model of Alzheimer's Disease

The processes by which neural stem cells (NSCs) and neural precursor cells (NPCs) transform into the characteristic lineages observed in Alzheimer's disease (AD) are poorly characterized. Understanding these processes is of critical importance due to the increased prevalence of AD and the lack...

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Autores principales: Li, Pan, Quan, Wei, Wang, Zengguang, Chen, Yuan, Zhang, Huihong, Zhou, Yuying
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7855712/
https://www.ncbi.nlm.nih.gov/pubmed/33551790
http://dx.doi.org/10.3389/fnagi.2020.616614
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author Li, Pan
Quan, Wei
Wang, Zengguang
Chen, Yuan
Zhang, Huihong
Zhou, Yuying
author_facet Li, Pan
Quan, Wei
Wang, Zengguang
Chen, Yuan
Zhang, Huihong
Zhou, Yuying
author_sort Li, Pan
collection PubMed
description The processes by which neural stem cells (NSCs) and neural precursor cells (NPCs) transform into the characteristic lineages observed in Alzheimer's disease (AD) are poorly characterized. Understanding these processes is of critical importance due to the increased prevalence of AD and the lack of effective AD strategies. Here, we used immunohistochemistry and Western blot to find out if MeCP2 was phosphorylated at a specific amino acid residue, Serine 421 (S421), and activated in response to AD-induced damage in amyloid precursor protein (APP)/PSl transgenic mice, altering its nuclear to cytoplasmic shuttling. Epigenetic examinations combined with chromatin immunoprecipitation and methylated DNA immunoprecipitation revealed that the translocation of MeCP2 from the nucleus to cytoplasm led to the loss of lineage-specific gene promoters (such as Gfap, Nestin, and Dcx), decreased transcriptional repression, and the activation of gene expression. Immunofluorescence data demonstrated that neurogenic progenitors with high levels of active phosphorylated MeCP2 at S421 (MeCP2 pS421) possessed a high probability of development into doublecortin (DCX)-expressing cells. AD7c-NTP will control neurogenic progenitor regeneration through its effects on MeCP2 pS421, leading to altered lineage-specific gene expression. This adds to the growing list of biological effects of AD7c-NTP in the brain and highlights MeCP2 as relevant to the plasticity of neural cells in the AD mice striatum.
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spelling pubmed-78557122021-02-04 AD7c-NTP Impairs Adult Striatal Neurogenesis by Affecting the Biological Function of MeCP2 in APP/PSl Transgenic Mouse Model of Alzheimer's Disease Li, Pan Quan, Wei Wang, Zengguang Chen, Yuan Zhang, Huihong Zhou, Yuying Front Aging Neurosci Neuroscience The processes by which neural stem cells (NSCs) and neural precursor cells (NPCs) transform into the characteristic lineages observed in Alzheimer's disease (AD) are poorly characterized. Understanding these processes is of critical importance due to the increased prevalence of AD and the lack of effective AD strategies. Here, we used immunohistochemistry and Western blot to find out if MeCP2 was phosphorylated at a specific amino acid residue, Serine 421 (S421), and activated in response to AD-induced damage in amyloid precursor protein (APP)/PSl transgenic mice, altering its nuclear to cytoplasmic shuttling. Epigenetic examinations combined with chromatin immunoprecipitation and methylated DNA immunoprecipitation revealed that the translocation of MeCP2 from the nucleus to cytoplasm led to the loss of lineage-specific gene promoters (such as Gfap, Nestin, and Dcx), decreased transcriptional repression, and the activation of gene expression. Immunofluorescence data demonstrated that neurogenic progenitors with high levels of active phosphorylated MeCP2 at S421 (MeCP2 pS421) possessed a high probability of development into doublecortin (DCX)-expressing cells. AD7c-NTP will control neurogenic progenitor regeneration through its effects on MeCP2 pS421, leading to altered lineage-specific gene expression. This adds to the growing list of biological effects of AD7c-NTP in the brain and highlights MeCP2 as relevant to the plasticity of neural cells in the AD mice striatum. Frontiers Media S.A. 2021-01-20 /pmc/articles/PMC7855712/ /pubmed/33551790 http://dx.doi.org/10.3389/fnagi.2020.616614 Text en Copyright © 2021 Li, Quan, Wang, Chen, Zhang and Zhou. http://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
Li, Pan
Quan, Wei
Wang, Zengguang
Chen, Yuan
Zhang, Huihong
Zhou, Yuying
AD7c-NTP Impairs Adult Striatal Neurogenesis by Affecting the Biological Function of MeCP2 in APP/PSl Transgenic Mouse Model of Alzheimer's Disease
title AD7c-NTP Impairs Adult Striatal Neurogenesis by Affecting the Biological Function of MeCP2 in APP/PSl Transgenic Mouse Model of Alzheimer's Disease
title_full AD7c-NTP Impairs Adult Striatal Neurogenesis by Affecting the Biological Function of MeCP2 in APP/PSl Transgenic Mouse Model of Alzheimer's Disease
title_fullStr AD7c-NTP Impairs Adult Striatal Neurogenesis by Affecting the Biological Function of MeCP2 in APP/PSl Transgenic Mouse Model of Alzheimer's Disease
title_full_unstemmed AD7c-NTP Impairs Adult Striatal Neurogenesis by Affecting the Biological Function of MeCP2 in APP/PSl Transgenic Mouse Model of Alzheimer's Disease
title_short AD7c-NTP Impairs Adult Striatal Neurogenesis by Affecting the Biological Function of MeCP2 in APP/PSl Transgenic Mouse Model of Alzheimer's Disease
title_sort ad7c-ntp impairs adult striatal neurogenesis by affecting the biological function of mecp2 in app/psl transgenic mouse model of alzheimer's disease
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7855712/
https://www.ncbi.nlm.nih.gov/pubmed/33551790
http://dx.doi.org/10.3389/fnagi.2020.616614
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