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Reduction of Amyloid Burden by Proliferated Homeostatic Microglia in Toxoplasma gondii-Infected Alzheimer’s Disease Model Mice
In this study, we confirmed that the number of resident homeostatic microglia increases during chronic Toxoplasma gondii infection. Given that the progression of Alzheimer’s disease (AD) worsens with the accumulation of amyloid β (Aβ) plaques, which are eliminated through microglial phagocytosis, we...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7975980/ https://www.ncbi.nlm.nih.gov/pubmed/33803262 http://dx.doi.org/10.3390/ijms22052764 |
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author | Shin, Ji-Hun Hwang, Young Sang Jung, Bong-Kwang Seo, Seung-Hwan Ham, Do-Won Shin, Eun-Hee |
author_facet | Shin, Ji-Hun Hwang, Young Sang Jung, Bong-Kwang Seo, Seung-Hwan Ham, Do-Won Shin, Eun-Hee |
author_sort | Shin, Ji-Hun |
collection | PubMed |
description | In this study, we confirmed that the number of resident homeostatic microglia increases during chronic Toxoplasma gondii infection. Given that the progression of Alzheimer’s disease (AD) worsens with the accumulation of amyloid β (Aβ) plaques, which are eliminated through microglial phagocytosis, we hypothesized that T. gondii-induced microglial proliferation would reduce AD progression. Therefore, we investigated the association between microglial proliferation and Aβ plaque burden using brain tissues isolated from 5XFAD AD mice (AD group) and T. gondii-infected AD mice (AD + Toxo group). In the AD + Toxo group, amyloid plaque burden significantly decreased compared with the AD group; conversely, homeostatic microglial proliferation, and number of plaque-associated microglia significantly increased. As most plaque-associated microglia shifted to the disease-associated microglia (DAM) phenotype in both AD and AD + Toxo groups and underwent apoptosis after the lysosomal degradation of phagocytosed Aβ plaques, this indicates that a sustained supply of homeostatic microglia is required for alleviating Aβ plaque burden. Thus, chronic T. gondii infection can induce microglial proliferation in the brains of mice with progressed AD; a sustained supply of homeostatic microglia is a promising prospect for AD treatment. |
format | Online Article Text |
id | pubmed-7975980 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-79759802021-03-20 Reduction of Amyloid Burden by Proliferated Homeostatic Microglia in Toxoplasma gondii-Infected Alzheimer’s Disease Model Mice Shin, Ji-Hun Hwang, Young Sang Jung, Bong-Kwang Seo, Seung-Hwan Ham, Do-Won Shin, Eun-Hee Int J Mol Sci Article In this study, we confirmed that the number of resident homeostatic microglia increases during chronic Toxoplasma gondii infection. Given that the progression of Alzheimer’s disease (AD) worsens with the accumulation of amyloid β (Aβ) plaques, which are eliminated through microglial phagocytosis, we hypothesized that T. gondii-induced microglial proliferation would reduce AD progression. Therefore, we investigated the association between microglial proliferation and Aβ plaque burden using brain tissues isolated from 5XFAD AD mice (AD group) and T. gondii-infected AD mice (AD + Toxo group). In the AD + Toxo group, amyloid plaque burden significantly decreased compared with the AD group; conversely, homeostatic microglial proliferation, and number of plaque-associated microglia significantly increased. As most plaque-associated microglia shifted to the disease-associated microglia (DAM) phenotype in both AD and AD + Toxo groups and underwent apoptosis after the lysosomal degradation of phagocytosed Aβ plaques, this indicates that a sustained supply of homeostatic microglia is required for alleviating Aβ plaque burden. Thus, chronic T. gondii infection can induce microglial proliferation in the brains of mice with progressed AD; a sustained supply of homeostatic microglia is a promising prospect for AD treatment. MDPI 2021-03-09 /pmc/articles/PMC7975980/ /pubmed/33803262 http://dx.doi.org/10.3390/ijms22052764 Text en © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Shin, Ji-Hun Hwang, Young Sang Jung, Bong-Kwang Seo, Seung-Hwan Ham, Do-Won Shin, Eun-Hee Reduction of Amyloid Burden by Proliferated Homeostatic Microglia in Toxoplasma gondii-Infected Alzheimer’s Disease Model Mice |
title | Reduction of Amyloid Burden by Proliferated Homeostatic Microglia in Toxoplasma gondii-Infected Alzheimer’s Disease Model Mice |
title_full | Reduction of Amyloid Burden by Proliferated Homeostatic Microglia in Toxoplasma gondii-Infected Alzheimer’s Disease Model Mice |
title_fullStr | Reduction of Amyloid Burden by Proliferated Homeostatic Microglia in Toxoplasma gondii-Infected Alzheimer’s Disease Model Mice |
title_full_unstemmed | Reduction of Amyloid Burden by Proliferated Homeostatic Microglia in Toxoplasma gondii-Infected Alzheimer’s Disease Model Mice |
title_short | Reduction of Amyloid Burden by Proliferated Homeostatic Microglia in Toxoplasma gondii-Infected Alzheimer’s Disease Model Mice |
title_sort | reduction of amyloid burden by proliferated homeostatic microglia in toxoplasma gondii-infected alzheimer’s disease model mice |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7975980/ https://www.ncbi.nlm.nih.gov/pubmed/33803262 http://dx.doi.org/10.3390/ijms22052764 |
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