Long-term aerobic exercise improves learning memory capacity and effects on oxidative stress levels and Keap1/Nrf2/GPX4 pathway in the hippocampus of APP/PS1 mice

ObjectiveTo examine the effects of long-term aerobic exercise on oxidative stress and learning memory ability of APP/PS1 mice, focusing on the hippocampal Keap1, Nrf2, HO-1, and GPX4 proteins.MethodsThirty APP/PS1 double transgenic AD mice were randomly divided into three groups: model group, short-...

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Main Authors: Shiyan Wang, Ye Zhou, Yucheng Wu, Yali Lang, Yajun Mao, Guoyuan Pan, Zhenzhen Gao
Format: Article
Language:English
Published: Frontiers Media S.A. 2024-11-01
Series:Frontiers in Neuroscience
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Online Access:https://www.frontiersin.org/articles/10.3389/fnins.2024.1505650/full
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author Shiyan Wang
Ye Zhou
Yucheng Wu
Yali Lang
Yajun Mao
Guoyuan Pan
Zhenzhen Gao
author_facet Shiyan Wang
Ye Zhou
Yucheng Wu
Yali Lang
Yajun Mao
Guoyuan Pan
Zhenzhen Gao
author_sort Shiyan Wang
collection DOAJ
description ObjectiveTo examine the effects of long-term aerobic exercise on oxidative stress and learning memory ability of APP/PS1 mice, focusing on the hippocampal Keap1, Nrf2, HO-1, and GPX4 proteins.MethodsThirty APP/PS1 double transgenic AD mice were randomly divided into three groups: model group, short-term exercise group, and long-term exercise group, with 10 mice in each group. Male non-transgenic mice of the same age served as the control group. The groups underwent swimming training for 6 weeks and 12 weeks, respectively. After the intervention, cognitive abilities were assessed using the Morris water maze test. Hippocampal tissue samples were analyzed for changes in superoxide dismutase (SOD) activity and malondialdehyde (MDA) content. ROS expression was observed using dihydroethidium probe, and Keap1, Nrf2, HO-1, and GPX4 protein levels were detected by Western blot analysis.ResultsAerobic exercise significantly reduced the escape latency and increased both the time spent in the target quadrant and the number crossing the platform compared to the model group (p < 0.05). In the hippocampus, aerobic exercise significantly reduced the MDA content, while significantly increased SOD activity (p < 0.05). The level of ROS in the hippocampal region was significantly reduced by aerobic exercise (p < 0.05), with decreased Keap1 protein expression of and increased Nrf2, HO-1, GPX4 protein expression (p < 0.05).ConclusionAerobic exercise enhances memory and learning abilities, improves cognitive function, and reduces the oxidative stress levels in the hippocampus of AD mice, which involves in the activation of Keap1/Nrf2/GPX4 pathway.
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spelling doaj-art-31d0bab55ff546589f8a435147a33ac32025-08-20T01:53:25ZengFrontiers Media S.A.Frontiers in Neuroscience1662-453X2024-11-011810.3389/fnins.2024.15056501505650Long-term aerobic exercise improves learning memory capacity and effects on oxidative stress levels and Keap1/Nrf2/GPX4 pathway in the hippocampus of APP/PS1 miceShiyan Wang0Ye Zhou1Yucheng Wu2Yali Lang3Yajun Mao4Guoyuan Pan5Zhenzhen Gao6Department of Rehabilitation Medicine, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, ChinaDepartment of Rehabilitation Medicine, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, ChinaDepartment of Rehabilitation Medicine, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, ChinaDepartment of Rehabilitation Medicine, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, ChinaDepartment of Rehabilitation Medicine, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, ChinaTongde Hospital of Zhejiang Province, Hangzhou, ChinaDepartment of Rehabilitation Medicine, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, ChinaObjectiveTo examine the effects of long-term aerobic exercise on oxidative stress and learning memory ability of APP/PS1 mice, focusing on the hippocampal Keap1, Nrf2, HO-1, and GPX4 proteins.MethodsThirty APP/PS1 double transgenic AD mice were randomly divided into three groups: model group, short-term exercise group, and long-term exercise group, with 10 mice in each group. Male non-transgenic mice of the same age served as the control group. The groups underwent swimming training for 6 weeks and 12 weeks, respectively. After the intervention, cognitive abilities were assessed using the Morris water maze test. Hippocampal tissue samples were analyzed for changes in superoxide dismutase (SOD) activity and malondialdehyde (MDA) content. ROS expression was observed using dihydroethidium probe, and Keap1, Nrf2, HO-1, and GPX4 protein levels were detected by Western blot analysis.ResultsAerobic exercise significantly reduced the escape latency and increased both the time spent in the target quadrant and the number crossing the platform compared to the model group (p < 0.05). In the hippocampus, aerobic exercise significantly reduced the MDA content, while significantly increased SOD activity (p < 0.05). The level of ROS in the hippocampal region was significantly reduced by aerobic exercise (p < 0.05), with decreased Keap1 protein expression of and increased Nrf2, HO-1, GPX4 protein expression (p < 0.05).ConclusionAerobic exercise enhances memory and learning abilities, improves cognitive function, and reduces the oxidative stress levels in the hippocampus of AD mice, which involves in the activation of Keap1/Nrf2/GPX4 pathway.https://www.frontiersin.org/articles/10.3389/fnins.2024.1505650/fullAlzheimer’s diseaseaerobic exerciseoxidative stressNrf2hippocampus
spellingShingle Shiyan Wang
Ye Zhou
Yucheng Wu
Yali Lang
Yajun Mao
Guoyuan Pan
Zhenzhen Gao
Long-term aerobic exercise improves learning memory capacity and effects on oxidative stress levels and Keap1/Nrf2/GPX4 pathway in the hippocampus of APP/PS1 mice
Frontiers in Neuroscience
Alzheimer’s disease
aerobic exercise
oxidative stress
Nrf2
hippocampus
title Long-term aerobic exercise improves learning memory capacity and effects on oxidative stress levels and Keap1/Nrf2/GPX4 pathway in the hippocampus of APP/PS1 mice
title_full Long-term aerobic exercise improves learning memory capacity and effects on oxidative stress levels and Keap1/Nrf2/GPX4 pathway in the hippocampus of APP/PS1 mice
title_fullStr Long-term aerobic exercise improves learning memory capacity and effects on oxidative stress levels and Keap1/Nrf2/GPX4 pathway in the hippocampus of APP/PS1 mice
title_full_unstemmed Long-term aerobic exercise improves learning memory capacity and effects on oxidative stress levels and Keap1/Nrf2/GPX4 pathway in the hippocampus of APP/PS1 mice
title_short Long-term aerobic exercise improves learning memory capacity and effects on oxidative stress levels and Keap1/Nrf2/GPX4 pathway in the hippocampus of APP/PS1 mice
title_sort long term aerobic exercise improves learning memory capacity and effects on oxidative stress levels and keap1 nrf2 gpx4 pathway in the hippocampus of app ps1 mice
topic Alzheimer’s disease
aerobic exercise
oxidative stress
Nrf2
hippocampus
url https://www.frontiersin.org/articles/10.3389/fnins.2024.1505650/full
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