Intermittent hypoxia treatment alleviates memory impairment in the 6-month-old APPswe/PS1dE9 mice and reduces amyloid beta accumulation and inflammation in the brain

Abstract Background Alzheimer’s disease (AD) is a progressive, degenerative, and terminal disease without cure. There is an urgent need for a new strategy to treat AD. The aim of this study was to investigate the effects of intermittent hypoxic treatment (IHT) on cognitive functions in a mouse model...

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Autores principales:	Xiangpei Yue, Yanzhao Zhou, Meng Qiao, Xingnan Zhao, Xin Huang, Tong Zhao, Xiang Cheng, Ming Fan, Yongqi Zhao, Ruoli Chen, Lingling Zhu
Formato:	article
Lenguaje:	EN
Publicado:	BMC 2021
Materias:	Alzheimer’s disease APPswe/PS1dE9 mice Intermittent hypoxia treatment Amyloid beta BACE1 Neuroinflammation Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Neurology. Diseases of the nervous system RC346-429
Acceso en línea:	https://doaj.org/article/ed26adcda63d4b01a593c7eb25408643
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spelling	oai:doaj.org-article:ed26adcda63d4b01a593c7eb254086432021-12-05T12:24:31ZIntermittent hypoxia treatment alleviates memory impairment in the 6-month-old APPswe/PS1dE9 mice and reduces amyloid beta accumulation and inflammation in the brain10.1186/s13195-021-00935-z1758-9193https://doaj.org/article/ed26adcda63d4b01a593c7eb254086432021-11-01T00:00:00Zhttps://doi.org/10.1186/s13195-021-00935-zhttps://doaj.org/toc/1758-9193Abstract Background Alzheimer’s disease (AD) is a progressive, degenerative, and terminal disease without cure. There is an urgent need for a new strategy to treat AD. The aim of this study was to investigate the effects of intermittent hypoxic treatment (IHT) on cognitive functions in a mouse model of AD and unravel the mechanism of action of IHT. Methods Six-month-old APPswe/PS1dE9 (APP/PS1) male mice were exposed to hypoxic environment (14.3% O2) 4 h/day for 14 days or 28 days. Cognitive functions were measured by Morris water maze test after either 14 days or 42 days of interval. Thereafter the distribution of amyloid plaque and microglial activation were determined by mouse brain immunohistochemistry, while the amyloid beta (Aβ) and inflammatory cytokines were measured by ELISA and Western Blot. Microarray was used for studying gene expressions in the hippocampus. Results IHT for 14 days or 28 days significantly improved the spatial memory ability of the 6-month-old APP/PS1 mice. The memory improvement by 14 days IHT lasted to 14 days, but not to 42 days. The level of Aβ plaques and neurofilament accumulations was reduced markedly after the IHT exposure. IHT reduced the pro-inflammatory cytokines IL-1β, IL-6 levels, and β-secretase cleavage of APP processing which implies reduced Aβ production. Microarray analysis revealed a large number of genes in the hippocampus were significantly altered which are known to be metabolism-regulated genes. Conclusions This study provides evidence of the beneficial effect of IHT on the progression of AD by alleviating memory impairment, reducing Aβ accumulation and inflammation in the brain. IHT can be developed as a novel measure to relieve the progression of AD by targeting multiple pathways in the AD pathogenesis.Xiangpei YueYanzhao ZhouMeng QiaoXingnan ZhaoXin HuangTong ZhaoXiang ChengMing FanYongqi ZhaoRuoli ChenLingling ZhuBMCarticleAlzheimer’s diseaseAPPswe/PS1dE9 miceIntermittent hypoxia treatmentAmyloid betaBACE1NeuroinflammationNeurosciences. Biological psychiatry. NeuropsychiatryRC321-571Neurology. Diseases of the nervous systemRC346-429ENAlzheimer’s Research & Therapy, Vol 13, Iss 1, Pp 1-16 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Alzheimer’s disease APPswe/PS1dE9 mice Intermittent hypoxia treatment Amyloid beta BACE1 Neuroinflammation Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Neurology. Diseases of the nervous system RC346-429
spellingShingle	Alzheimer’s disease APPswe/PS1dE9 mice Intermittent hypoxia treatment Amyloid beta BACE1 Neuroinflammation Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Neurology. Diseases of the nervous system RC346-429 Xiangpei Yue Yanzhao Zhou Meng Qiao Xingnan Zhao Xin Huang Tong Zhao Xiang Cheng Ming Fan Yongqi Zhao Ruoli Chen Lingling Zhu Intermittent hypoxia treatment alleviates memory impairment in the 6-month-old APPswe/PS1dE9 mice and reduces amyloid beta accumulation and inflammation in the brain
description	Abstract Background Alzheimer’s disease (AD) is a progressive, degenerative, and terminal disease without cure. There is an urgent need for a new strategy to treat AD. The aim of this study was to investigate the effects of intermittent hypoxic treatment (IHT) on cognitive functions in a mouse model of AD and unravel the mechanism of action of IHT. Methods Six-month-old APPswe/PS1dE9 (APP/PS1) male mice were exposed to hypoxic environment (14.3% O2) 4 h/day for 14 days or 28 days. Cognitive functions were measured by Morris water maze test after either 14 days or 42 days of interval. Thereafter the distribution of amyloid plaque and microglial activation were determined by mouse brain immunohistochemistry, while the amyloid beta (Aβ) and inflammatory cytokines were measured by ELISA and Western Blot. Microarray was used for studying gene expressions in the hippocampus. Results IHT for 14 days or 28 days significantly improved the spatial memory ability of the 6-month-old APP/PS1 mice. The memory improvement by 14 days IHT lasted to 14 days, but not to 42 days. The level of Aβ plaques and neurofilament accumulations was reduced markedly after the IHT exposure. IHT reduced the pro-inflammatory cytokines IL-1β, IL-6 levels, and β-secretase cleavage of APP processing which implies reduced Aβ production. Microarray analysis revealed a large number of genes in the hippocampus were significantly altered which are known to be metabolism-regulated genes. Conclusions This study provides evidence of the beneficial effect of IHT on the progression of AD by alleviating memory impairment, reducing Aβ accumulation and inflammation in the brain. IHT can be developed as a novel measure to relieve the progression of AD by targeting multiple pathways in the AD pathogenesis.
format	article
author	Xiangpei Yue Yanzhao Zhou Meng Qiao Xingnan Zhao Xin Huang Tong Zhao Xiang Cheng Ming Fan Yongqi Zhao Ruoli Chen Lingling Zhu
author_facet	Xiangpei Yue Yanzhao Zhou Meng Qiao Xingnan Zhao Xin Huang Tong Zhao Xiang Cheng Ming Fan Yongqi Zhao Ruoli Chen Lingling Zhu
author_sort	Xiangpei Yue
title	Intermittent hypoxia treatment alleviates memory impairment in the 6-month-old APPswe/PS1dE9 mice and reduces amyloid beta accumulation and inflammation in the brain
title_short	Intermittent hypoxia treatment alleviates memory impairment in the 6-month-old APPswe/PS1dE9 mice and reduces amyloid beta accumulation and inflammation in the brain
title_full	Intermittent hypoxia treatment alleviates memory impairment in the 6-month-old APPswe/PS1dE9 mice and reduces amyloid beta accumulation and inflammation in the brain
title_fullStr	Intermittent hypoxia treatment alleviates memory impairment in the 6-month-old APPswe/PS1dE9 mice and reduces amyloid beta accumulation and inflammation in the brain
title_full_unstemmed	Intermittent hypoxia treatment alleviates memory impairment in the 6-month-old APPswe/PS1dE9 mice and reduces amyloid beta accumulation and inflammation in the brain
title_sort	intermittent hypoxia treatment alleviates memory impairment in the 6-month-old appswe/ps1de9 mice and reduces amyloid beta accumulation and inflammation in the brain
publisher	BMC
publishDate	2021
url	https://doaj.org/article/ed26adcda63d4b01a593c7eb25408643
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Intermittent hypoxia treatment alleviates memory impairment in the 6-month-old APPswe/PS1dE9 mice and reduces amyloid beta accumulation and inflammation in the brain

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