Aerobic Exercise Ameliorates Alzheimer’s Disease-Like Pathology by Regulating Hepatic Phagocytosis of Aβ

Background: Alzheimer’s disease (AD) is a neurodegenerative disease which significantly and negatively affects families and society. Aerobic exercise serves as a non-pharmacological strategy, potentially safeguarding against cognitive decline and lowering the risk of AD. However,...

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Main Authors: Qing Wang, Feng-Rui Hu, Xing-Chun Gou, Shan Wang, Nai-Chun Ji
Format: Article
Language:English
Published: IMR Press 2025-04-01
Series:Frontiers in Bioscience-Landmark
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Online Access:https://www.imrpress.com/journal/FBL/30/4/10.31083/FBL36597
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author Qing Wang
Feng-Rui Hu
Xing-Chun Gou
Shan Wang
Nai-Chun Ji
author_facet Qing Wang
Feng-Rui Hu
Xing-Chun Gou
Shan Wang
Nai-Chun Ji
author_sort Qing Wang
collection DOAJ
description Background: Alzheimer’s disease (AD) is a neurodegenerative disease which significantly and negatively affects families and society. Aerobic exercise serves as a non-pharmacological strategy, potentially safeguarding against cognitive decline and lowering the risk of AD. However, how aerobic exercise ameliorates AD remains unknown. This study investigated the effects of two types of aerobic exercise, including aerobic interval training (AIT) and aerobic continuous training (ACT), on cognitive and exploratory function, brain histopathology, and hepatic amyloid beta (Aβ) clearance in amyloid precursor protein/presenilin-1 double transgenic (APP/PS1) transgenic mice. Methods: Twenty-four six-month-old male APP/PS1 transgenic mice (body weight: 20–22 g) were used to establish the AD model. APP/PS1 transgenic mice were randomly assigned to one of the three groups: rest (AD group, n = 8), aerobic interval training (AIT group, n = 8), and aerobic continuous training (ACT group, n = 8). The exploration ability and anxiety of AD mice were measured using the open-field test. Learning and memory of AD mice were detected using the novel object recognition test, Y-maze test, and Morris water maze test. Neuronal damage was analyzed using hematoxylin and eosin staining and Nissl staining. Aβ deposition in the brain was detected using a thioflavin-S fluorescence assay and immunofluorescence. The mechanisms underlying hepatic Aβ clearance were investigated using an immunofluorescence assay and western blotting. Data were analyzed using one-way ANOVA with Tukey’s post hoc test, and p < 0.05 was deemed statistically significant. Results: The results revealed that both AIT and ACT improved the recognition memory and exploration ability of mice after 8 weeks of intervention. Additionally, both forms of aerobic exercise significantly mitigated neuronal damage and Aβ deposition in the brain and improved the hepatic clearance of Aβ. Conclusions: Our findings indicated that AIT and ACT can improve cognitive deficits in APP/PS1 mice, potentially by increasing the hepatic phagocytic capacity of Aβ. Hepatic clearance of Aβ may serve as a supplementary mechanism by which aerobic exercise can improve AD.
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spelling doaj-art-0c07fb0ffe6d4f42b0a10de80963f9102025-08-20T03:53:39ZengIMR PressFrontiers in Bioscience-Landmark2768-67012025-04-013043659710.31083/FBL36597S2768-6701(25)01698-3Aerobic Exercise Ameliorates Alzheimer’s Disease-Like Pathology by Regulating Hepatic Phagocytosis of AβQing Wang0Feng-Rui Hu1Xing-Chun Gou2Shan Wang3Nai-Chun Ji4Shaanxi Key Laboratory of Brain Disorders & Institute of Basic and Translational Medicine, Xi’an Medical University, 710021 Xi’an, Shaanxi, ChinaShaanxi Key Laboratory of Brain Disorders & Institute of Basic and Translational Medicine, Xi’an Medical University, 710021 Xi’an, Shaanxi, ChinaShaanxi Key Laboratory of Brain Disorders & Institute of Basic and Translational Medicine, Xi’an Medical University, 710021 Xi’an, Shaanxi, ChinaShaanxi Key Laboratory of Brain Disorders & Institute of Basic and Translational Medicine, Xi’an Medical University, 710021 Xi’an, Shaanxi, ChinaCenter for Blockchain & Healthcare Service, Xi’an Medical University, 710021 Xi’an, Shaanxi, ChinaBackground: Alzheimer’s disease (AD) is a neurodegenerative disease which significantly and negatively affects families and society. Aerobic exercise serves as a non-pharmacological strategy, potentially safeguarding against cognitive decline and lowering the risk of AD. However, how aerobic exercise ameliorates AD remains unknown. This study investigated the effects of two types of aerobic exercise, including aerobic interval training (AIT) and aerobic continuous training (ACT), on cognitive and exploratory function, brain histopathology, and hepatic amyloid beta (Aβ) clearance in amyloid precursor protein/presenilin-1 double transgenic (APP/PS1) transgenic mice. Methods: Twenty-four six-month-old male APP/PS1 transgenic mice (body weight: 20–22 g) were used to establish the AD model. APP/PS1 transgenic mice were randomly assigned to one of the three groups: rest (AD group, n = 8), aerobic interval training (AIT group, n = 8), and aerobic continuous training (ACT group, n = 8). The exploration ability and anxiety of AD mice were measured using the open-field test. Learning and memory of AD mice were detected using the novel object recognition test, Y-maze test, and Morris water maze test. Neuronal damage was analyzed using hematoxylin and eosin staining and Nissl staining. Aβ deposition in the brain was detected using a thioflavin-S fluorescence assay and immunofluorescence. The mechanisms underlying hepatic Aβ clearance were investigated using an immunofluorescence assay and western blotting. Data were analyzed using one-way ANOVA with Tukey’s post hoc test, and p < 0.05 was deemed statistically significant. Results: The results revealed that both AIT and ACT improved the recognition memory and exploration ability of mice after 8 weeks of intervention. Additionally, both forms of aerobic exercise significantly mitigated neuronal damage and Aβ deposition in the brain and improved the hepatic clearance of Aβ. Conclusions: Our findings indicated that AIT and ACT can improve cognitive deficits in APP/PS1 mice, potentially by increasing the hepatic phagocytic capacity of Aβ. Hepatic clearance of Aβ may serve as a supplementary mechanism by which aerobic exercise can improve AD.https://www.imrpress.com/journal/FBL/30/4/10.31083/FBL36597alzheimer’s diseaseaerobic exerciseaβ clearancehepatic phagocytosis
spellingShingle Qing Wang
Feng-Rui Hu
Xing-Chun Gou
Shan Wang
Nai-Chun Ji
Aerobic Exercise Ameliorates Alzheimer’s Disease-Like Pathology by Regulating Hepatic Phagocytosis of Aβ
Frontiers in Bioscience-Landmark
alzheimer’s disease
aerobic exercise
aβ clearance
hepatic phagocytosis
title Aerobic Exercise Ameliorates Alzheimer’s Disease-Like Pathology by Regulating Hepatic Phagocytosis of Aβ
title_full Aerobic Exercise Ameliorates Alzheimer’s Disease-Like Pathology by Regulating Hepatic Phagocytosis of Aβ
title_fullStr Aerobic Exercise Ameliorates Alzheimer’s Disease-Like Pathology by Regulating Hepatic Phagocytosis of Aβ
title_full_unstemmed Aerobic Exercise Ameliorates Alzheimer’s Disease-Like Pathology by Regulating Hepatic Phagocytosis of Aβ
title_short Aerobic Exercise Ameliorates Alzheimer’s Disease-Like Pathology by Regulating Hepatic Phagocytosis of Aβ
title_sort aerobic exercise ameliorates alzheimer s disease like pathology by regulating hepatic phagocytosis of aβ
topic alzheimer’s disease
aerobic exercise
aβ clearance
hepatic phagocytosis
url https://www.imrpress.com/journal/FBL/30/4/10.31083/FBL36597
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