Interdependence of neural network dysfunction and microglial alterations in Alzheimer’s disease-related models

Summary: Nonconvulsive epileptiform activity and microglial alterations have been detected in people with Alzheimer’s disease (AD) and related mouse models. However, the relationship between these abnormalities remains to be elucidated. We suppressed epileptiform activity by treatment with the antie...

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Autores principales:	Melanie Das, Wenjie Mao, Eric Shao, Soniya Tamhankar, Gui-Qiu Yu, Xinxing Yu, Kaitlyn Ho, Xin Wang, Jiaming Wang, Lennart Mucke
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	Neuroscience Molecular neuroscience Clinical neuroscience Science Q
Acceso en línea:	https://doaj.org/article/e869c5ad52c44f1d85777a893829f213
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spelling	oai:doaj.org-article:e869c5ad52c44f1d85777a893829f2132021-11-20T05:08:49ZInterdependence of neural network dysfunction and microglial alterations in Alzheimer’s disease-related models2589-004210.1016/j.isci.2021.103245https://doaj.org/article/e869c5ad52c44f1d85777a893829f2132021-11-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S258900422101213Xhttps://doaj.org/toc/2589-0042Summary: Nonconvulsive epileptiform activity and microglial alterations have been detected in people with Alzheimer’s disease (AD) and related mouse models. However, the relationship between these abnormalities remains to be elucidated. We suppressed epileptiform activity by treatment with the antiepileptic drug levetiracetam or by genetic ablation of tau and found that these interventions reversed or prevented aberrant microglial gene expression in brain tissues of aged human amyloid precursor protein transgenic mice, which simulate several key aspects of AD. The most robustly modulated genes included multiple factors previously implicated in AD pathogenesis, including TREM2, the hypofunction of which increases disease risk. Genetic reduction of TREM2 exacerbated epileptiform activity after mice were injected with kainate. We conclude that AD-related epileptiform activity markedly changes the molecular profile of microglia, inducing both maladaptive and adaptive alterations in their activities. Increased expression of TREM2 seems to support microglial activities that counteract this type of network dysfunction.Melanie DasWenjie MaoEric ShaoSoniya TamhankarGui-Qiu YuXinxing YuKaitlyn HoXin WangJiaming WangLennart MuckeElsevierarticleNeuroscienceMolecular neuroscienceClinical neuroscienceScienceQENiScience, Vol 24, Iss 11, Pp 103245- (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Neuroscience Molecular neuroscience Clinical neuroscience Science Q
spellingShingle	Neuroscience Molecular neuroscience Clinical neuroscience Science Q Melanie Das Wenjie Mao Eric Shao Soniya Tamhankar Gui-Qiu Yu Xinxing Yu Kaitlyn Ho Xin Wang Jiaming Wang Lennart Mucke Interdependence of neural network dysfunction and microglial alterations in Alzheimer’s disease-related models
description	Summary: Nonconvulsive epileptiform activity and microglial alterations have been detected in people with Alzheimer’s disease (AD) and related mouse models. However, the relationship between these abnormalities remains to be elucidated. We suppressed epileptiform activity by treatment with the antiepileptic drug levetiracetam or by genetic ablation of tau and found that these interventions reversed or prevented aberrant microglial gene expression in brain tissues of aged human amyloid precursor protein transgenic mice, which simulate several key aspects of AD. The most robustly modulated genes included multiple factors previously implicated in AD pathogenesis, including TREM2, the hypofunction of which increases disease risk. Genetic reduction of TREM2 exacerbated epileptiform activity after mice were injected with kainate. We conclude that AD-related epileptiform activity markedly changes the molecular profile of microglia, inducing both maladaptive and adaptive alterations in their activities. Increased expression of TREM2 seems to support microglial activities that counteract this type of network dysfunction.
format	article
author	Melanie Das Wenjie Mao Eric Shao Soniya Tamhankar Gui-Qiu Yu Xinxing Yu Kaitlyn Ho Xin Wang Jiaming Wang Lennart Mucke
author_facet	Melanie Das Wenjie Mao Eric Shao Soniya Tamhankar Gui-Qiu Yu Xinxing Yu Kaitlyn Ho Xin Wang Jiaming Wang Lennart Mucke
author_sort	Melanie Das
title	Interdependence of neural network dysfunction and microglial alterations in Alzheimer’s disease-related models
title_short	Interdependence of neural network dysfunction and microglial alterations in Alzheimer’s disease-related models
title_full	Interdependence of neural network dysfunction and microglial alterations in Alzheimer’s disease-related models
title_fullStr	Interdependence of neural network dysfunction and microglial alterations in Alzheimer’s disease-related models
title_full_unstemmed	Interdependence of neural network dysfunction and microglial alterations in Alzheimer’s disease-related models
title_sort	interdependence of neural network dysfunction and microglial alterations in alzheimer’s disease-related models
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/e869c5ad52c44f1d85777a893829f213
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Interdependence of neural network dysfunction and microglial alterations in Alzheimer’s disease-related models

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