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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doaj-7e1c7b3291b74308b9d953528844c89d2021-01-20T06:57:50ZengFrontiers Media S.A.Frontiers in Aging Neuroscience1663-43652021-01-011210.3389/fnagi.2020.616614616614AD7c-NTP Impairs Adult Striatal Neurogenesis by Affecting the Biological Function of MeCP2 in APP/PSl Transgenic Mouse Model of Alzheimer's DiseasePan Li0Pan Li1Wei Quan2Wei Quan3Zengguang Wang4Zengguang Wang5Yuan Chen6Yuan Chen7Huihong Zhang8Huihong Zhang9Yuying Zhou10Yuying Zhou11Department of Neurology, Tianjin Huanhu Hospital Affiliated to Nankai University, Tianjin, ChinaTianjin Key Laboratory of Cerebral Vascular and Neurodegenerative Diseases, Tianjin Neurosurgery Institute, Tianjin Huanhu Hospital Affiliated to Nankai University, Tianjin, ChinaDepartment of Neurosurgery, General Hospital of Tianjin Medical University, Tianjin, ChinaTianjin Key Laboratory of Injuries, Variations and Regeneration of Nervous System, Tianjin Neurological Institute, Tianjin, ChinaDepartment of Neurosurgery, General Hospital of Tianjin Medical University, Tianjin, ChinaTianjin Key Laboratory of Injuries, Variations and Regeneration of Nervous System, Tianjin Neurological Institute, Tianjin, ChinaDepartment of Neurology, Tianjin Huanhu Hospital Affiliated to Nankai University, Tianjin, ChinaTianjin Key Laboratory of Cerebral Vascular and Neurodegenerative Diseases, Tianjin Neurosurgery Institute, Tianjin Huanhu Hospital Affiliated to Nankai University, Tianjin, ChinaDepartment of Neurology, Tianjin Huanhu Hospital Affiliated to Nankai University, Tianjin, ChinaTianjin Key Laboratory of Cerebral Vascular and Neurodegenerative Diseases, Tianjin Neurosurgery Institute, Tianjin Huanhu Hospital Affiliated to Nankai University, Tianjin, ChinaDepartment of Neurology, Tianjin Huanhu Hospital Affiliated to Nankai University, Tianjin, ChinaTianjin Key Laboratory of Cerebral Vascular and Neurodegenerative Diseases, Tianjin Neurosurgery Institute, Tianjin Huanhu Hospital Affiliated to Nankai University, Tianjin, ChinaThe 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.https://www.frontiersin.org/articles/10.3389/fnagi.2020.616614/fullAlzheimer diseaseAD7c-NTPneurogeneisneural plasticityDNA methylationmethyl-CpG binding protein 2 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Pan Li Pan Li Wei Quan Wei Quan Zengguang Wang Zengguang Wang Yuan Chen Yuan Chen Huihong Zhang Huihong Zhang Yuying Zhou Yuying Zhou |
spellingShingle |
Pan Li Pan Li Wei Quan Wei Quan Zengguang Wang Zengguang Wang Yuan Chen Yuan Chen Huihong Zhang Huihong Zhang Yuying Zhou Yuying Zhou AD7c-NTP Impairs Adult Striatal Neurogenesis by Affecting the Biological Function of MeCP2 in APP/PSl Transgenic Mouse Model of Alzheimer's Disease Frontiers in Aging Neuroscience Alzheimer disease AD7c-NTP neurogeneis neural plasticity DNA methylation methyl-CpG binding protein 2 |
author_facet |
Pan Li Pan Li Wei Quan Wei Quan Zengguang Wang Zengguang Wang Yuan Chen Yuan Chen Huihong Zhang Huihong Zhang Yuying Zhou Yuying Zhou |
author_sort |
Pan Li |
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_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_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_sort |
ad7c-ntp impairs adult striatal neurogenesis by affecting the biological function of mecp2 in app/psl transgenic mouse model of alzheimer's disease |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Aging Neuroscience |
issn |
1663-4365 |
publishDate |
2021-01-01 |
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. |
topic |
Alzheimer disease AD7c-NTP neurogeneis neural plasticity DNA methylation methyl-CpG binding protein 2 |
url |
https://www.frontiersin.org/articles/10.3389/fnagi.2020.616614/full |
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