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Isoniazid improves cognitive performance, clears Aβ plaques, and protects dendritic synapses in APP/PS1 transgenic mice

BACKGROUND AND OBJECTIVE: Alzheimer’s disease (AD) is characterized by amyloid β (Aβ) aggregation and neuroinflammation. This study aimed to investigate the therapeutic effect of isoniazid (INH) against AD. METHODS: The APP/PS1 transgenic mouse model of AD was adopted. The APP/PS1 mice received oral...

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Autores principales: Chen, Jiacheng, Guo, Ning, Ruan, Yuting, Mai, Yingren, Liao, Wang, Feng, Yanqing
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9892762/
https://www.ncbi.nlm.nih.gov/pubmed/36743440
http://dx.doi.org/10.3389/fnagi.2023.1105095
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author Chen, Jiacheng
Guo, Ning
Ruan, Yuting
Mai, Yingren
Liao, Wang
Feng, Yanqing
author_facet Chen, Jiacheng
Guo, Ning
Ruan, Yuting
Mai, Yingren
Liao, Wang
Feng, Yanqing
author_sort Chen, Jiacheng
collection PubMed
description BACKGROUND AND OBJECTIVE: Alzheimer’s disease (AD) is characterized by amyloid β (Aβ) aggregation and neuroinflammation. This study aimed to investigate the therapeutic effect of isoniazid (INH) against AD. METHODS: The APP/PS1 transgenic mouse model of AD was adopted. The APP/PS1 mice received oral INH (45 mg/kg/d) for 14 days. The cognitive capability was assessed by the Morris Water Maze test. Amyloid plaques and Aβ levels were determined by immunohistochemistry and ELISA assay. The dendritic spines were analyzed by DiOlistic labeling. Immunofluorescence staining was used to observe the microglia and astrocytes. RESULTS: The Morris Water Maze test suggested that INH administration can effectively attenuate the reference memory deficit and improve the working memory of the APP/PS1 mice compared to the untreated mice (all p < 0.001). INH significantly decreased the Aβ plaques in the hippocampus and cortex and reduced the levels of Aβ(1-40) and Aβ(1-42) in the brain homogenates, cerebrospinal fluid, and serum (all p < 0.001). INH also inhibited enzyme activities of β-site amyloid precursor protein cleaving enzyme 1 (BACE1, p < 0.05) and monoamine oxidase B (Mao-b, p < 0.01). INH significantly increased the protrusion density in the hippocampus (p < 0.01). Immunofluorescence staining revealed that INH significantly reduced the number of activated microglia and astrocytes around the Aβ plaques (both p < 0.01). CONCLUSION: Isoniazid administration effectively improved cognitive performance, cleared Aβ plaques, protected dendritic synapses, and reduced innate immune cells around the Aβ plaques, suggesting that INH could be a potential drug for AD treatment.
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spelling pubmed-98927622023-02-03 Isoniazid improves cognitive performance, clears Aβ plaques, and protects dendritic synapses in APP/PS1 transgenic mice Chen, Jiacheng Guo, Ning Ruan, Yuting Mai, Yingren Liao, Wang Feng, Yanqing Front Aging Neurosci Aging Neuroscience BACKGROUND AND OBJECTIVE: Alzheimer’s disease (AD) is characterized by amyloid β (Aβ) aggregation and neuroinflammation. This study aimed to investigate the therapeutic effect of isoniazid (INH) against AD. METHODS: The APP/PS1 transgenic mouse model of AD was adopted. The APP/PS1 mice received oral INH (45 mg/kg/d) for 14 days. The cognitive capability was assessed by the Morris Water Maze test. Amyloid plaques and Aβ levels were determined by immunohistochemistry and ELISA assay. The dendritic spines were analyzed by DiOlistic labeling. Immunofluorescence staining was used to observe the microglia and astrocytes. RESULTS: The Morris Water Maze test suggested that INH administration can effectively attenuate the reference memory deficit and improve the working memory of the APP/PS1 mice compared to the untreated mice (all p < 0.001). INH significantly decreased the Aβ plaques in the hippocampus and cortex and reduced the levels of Aβ(1-40) and Aβ(1-42) in the brain homogenates, cerebrospinal fluid, and serum (all p < 0.001). INH also inhibited enzyme activities of β-site amyloid precursor protein cleaving enzyme 1 (BACE1, p < 0.05) and monoamine oxidase B (Mao-b, p < 0.01). INH significantly increased the protrusion density in the hippocampus (p < 0.01). Immunofluorescence staining revealed that INH significantly reduced the number of activated microglia and astrocytes around the Aβ plaques (both p < 0.01). CONCLUSION: Isoniazid administration effectively improved cognitive performance, cleared Aβ plaques, protected dendritic synapses, and reduced innate immune cells around the Aβ plaques, suggesting that INH could be a potential drug for AD treatment. Frontiers Media S.A. 2023-01-19 /pmc/articles/PMC9892762/ /pubmed/36743440 http://dx.doi.org/10.3389/fnagi.2023.1105095 Text en Copyright © 2023 Chen, Guo, Ruan, Mai, Liao and Feng. https://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 Aging Neuroscience
Chen, Jiacheng
Guo, Ning
Ruan, Yuting
Mai, Yingren
Liao, Wang
Feng, Yanqing
Isoniazid improves cognitive performance, clears Aβ plaques, and protects dendritic synapses in APP/PS1 transgenic mice
title Isoniazid improves cognitive performance, clears Aβ plaques, and protects dendritic synapses in APP/PS1 transgenic mice
title_full Isoniazid improves cognitive performance, clears Aβ plaques, and protects dendritic synapses in APP/PS1 transgenic mice
title_fullStr Isoniazid improves cognitive performance, clears Aβ plaques, and protects dendritic synapses in APP/PS1 transgenic mice
title_full_unstemmed Isoniazid improves cognitive performance, clears Aβ plaques, and protects dendritic synapses in APP/PS1 transgenic mice
title_short Isoniazid improves cognitive performance, clears Aβ plaques, and protects dendritic synapses in APP/PS1 transgenic mice
title_sort isoniazid improves cognitive performance, clears aβ plaques, and protects dendritic synapses in app/ps1 transgenic mice
topic Aging Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9892762/
https://www.ncbi.nlm.nih.gov/pubmed/36743440
http://dx.doi.org/10.3389/fnagi.2023.1105095
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