Microglia-Based Sex-Biased Neuropathology in Early-Stage Alzheimer’s Disease Model Mice and the Potential Pharmacologic Efficacy of Dioscin

Alzheimer’s disease (AD), the most common form of dementia, is characterized by amyloid-β (Aβ) accumulation, microglia-associated neuroinflammation, and synaptic loss. The detailed neuropathologic characteristics in early-stage AD, however, are largely unclear. We evaluated the pathologic brain alte...

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Autores principales:	Xiao Liu, Qian Zhou, Jia-He Zhang, Ke-Yong Wang, Takashi Saito, Takaomi C. Saido, Xiaoying Wang, Xiumei Gao, Kagaku Azuma
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	Alzheimer’s disease <i>A</i><i>pp<sup>NL-G-F</sup></i> dioscin amyloid-β synaptic dysfunction microglia Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/0f374323079340529d0aaedd0f68f9b4
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spelling	oai:doaj.org-article:0f374323079340529d0aaedd0f68f9b42021-11-25T17:13:24ZMicroglia-Based Sex-Biased Neuropathology in Early-Stage Alzheimer’s Disease Model Mice and the Potential Pharmacologic Efficacy of Dioscin10.3390/cells101132612073-4409https://doaj.org/article/0f374323079340529d0aaedd0f68f9b42021-11-01T00:00:00Zhttps://www.mdpi.com/2073-4409/10/11/3261https://doaj.org/toc/2073-4409Alzheimer’s disease (AD), the most common form of dementia, is characterized by amyloid-β (Aβ) accumulation, microglia-associated neuroinflammation, and synaptic loss. The detailed neuropathologic characteristics in early-stage AD, however, are largely unclear. We evaluated the pathologic brain alterations in young adult App knock-in model <i>App<sup>NL-G-F</sup></i> mice at 3 and 6 months of age, which corresponds to early-stage AD. At 3 months of age, microglia expression in the cortex and hippocampus was significantly decreased. By the age of 6 months, the number and function of the microglia increased, accompanied by progressive amyloid-β deposition, synaptic dysfunction, neuroinflammation, and dysregulation of β-catenin and NF-κB signaling pathways. The neuropathologic changes were more severe in female mice than in male mice. Oral administration of dioscin, a natural product, ameliorated the neuropathologic alterations in young <i>App<sup>NL-G-F</sup></i> mice. Our findings revealed microglia-based sex-differential neuropathologic changes in a mouse model of early-stage AD and therapeutic efficacy of dioscin on the brain lesions. Dioscin may represent a potential treatment for AD.Xiao LiuQian ZhouJia-He ZhangKe-Yong WangTakashi SaitoTakaomi C. SaidoXiaoying WangXiumei GaoKagaku AzumaMDPI AGarticleAlzheimer’s disease<i>A</i><i>pp<sup>NL-G-F</sup></i>dioscinamyloid-βsynaptic dysfunctionmicrogliaBiology (General)QH301-705.5ENCells, Vol 10, Iss 3261, p 3261 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Alzheimer’s disease <i>A</i><i>pp<sup>NL-G-F</sup></i> dioscin amyloid-β synaptic dysfunction microglia Biology (General) QH301-705.5
spellingShingle	Alzheimer’s disease <i>A</i><i>pp<sup>NL-G-F</sup></i> dioscin amyloid-β synaptic dysfunction microglia Biology (General) QH301-705.5 Xiao Liu Qian Zhou Jia-He Zhang Ke-Yong Wang Takashi Saito Takaomi C. Saido Xiaoying Wang Xiumei Gao Kagaku Azuma Microglia-Based Sex-Biased Neuropathology in Early-Stage Alzheimer’s Disease Model Mice and the Potential Pharmacologic Efficacy of Dioscin
description	Alzheimer’s disease (AD), the most common form of dementia, is characterized by amyloid-β (Aβ) accumulation, microglia-associated neuroinflammation, and synaptic loss. The detailed neuropathologic characteristics in early-stage AD, however, are largely unclear. We evaluated the pathologic brain alterations in young adult App knock-in model <i>App<sup>NL-G-F</sup></i> mice at 3 and 6 months of age, which corresponds to early-stage AD. At 3 months of age, microglia expression in the cortex and hippocampus was significantly decreased. By the age of 6 months, the number and function of the microglia increased, accompanied by progressive amyloid-β deposition, synaptic dysfunction, neuroinflammation, and dysregulation of β-catenin and NF-κB signaling pathways. The neuropathologic changes were more severe in female mice than in male mice. Oral administration of dioscin, a natural product, ameliorated the neuropathologic alterations in young <i>App<sup>NL-G-F</sup></i> mice. Our findings revealed microglia-based sex-differential neuropathologic changes in a mouse model of early-stage AD and therapeutic efficacy of dioscin on the brain lesions. Dioscin may represent a potential treatment for AD.
format	article
author	Xiao Liu Qian Zhou Jia-He Zhang Ke-Yong Wang Takashi Saito Takaomi C. Saido Xiaoying Wang Xiumei Gao Kagaku Azuma
author_facet	Xiao Liu Qian Zhou Jia-He Zhang Ke-Yong Wang Takashi Saito Takaomi C. Saido Xiaoying Wang Xiumei Gao Kagaku Azuma
author_sort	Xiao Liu
title	Microglia-Based Sex-Biased Neuropathology in Early-Stage Alzheimer’s Disease Model Mice and the Potential Pharmacologic Efficacy of Dioscin
title_short	Microglia-Based Sex-Biased Neuropathology in Early-Stage Alzheimer’s Disease Model Mice and the Potential Pharmacologic Efficacy of Dioscin
title_full	Microglia-Based Sex-Biased Neuropathology in Early-Stage Alzheimer’s Disease Model Mice and the Potential Pharmacologic Efficacy of Dioscin
title_fullStr	Microglia-Based Sex-Biased Neuropathology in Early-Stage Alzheimer’s Disease Model Mice and the Potential Pharmacologic Efficacy of Dioscin
title_full_unstemmed	Microglia-Based Sex-Biased Neuropathology in Early-Stage Alzheimer’s Disease Model Mice and the Potential Pharmacologic Efficacy of Dioscin
title_sort	microglia-based sex-biased neuropathology in early-stage alzheimer’s disease model mice and the potential pharmacologic efficacy of dioscin
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/0f374323079340529d0aaedd0f68f9b4
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Microglia-Based Sex-Biased Neuropathology in Early-Stage Alzheimer’s Disease Model Mice and the Potential Pharmacologic Efficacy of Dioscin

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