Hippocampal SIRT1 signaling mediates the ameliorative effect of treadmill exercise on anxiety- and depression-like behavior in APP/PS1 mice
ObjectiveAnxiety and depression-like symptoms occur in the early stages of Alzheimer’s disease. Hippocampal Sirtuin 1 (SIRT1) signaling mediates anxiety- and depression-like behavior. Exercise training improves anxiety and depression-like behavior in various disease models, such as the rat chronic r...
Saved in:
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2024-12-01
|
| Series: | Frontiers in Aging Neuroscience |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fnagi.2024.1489214/full |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850065365262925824 |
|---|---|
| author | Yarong Wang Yarong Wang Rongxing Zhang Yumin Jiang Jingwen Liao Jingwen Liao Lianwei Mu Lianwei Mu Min Hu Min Hu |
| author_facet | Yarong Wang Yarong Wang Rongxing Zhang Yumin Jiang Jingwen Liao Jingwen Liao Lianwei Mu Lianwei Mu Min Hu Min Hu |
| author_sort | Yarong Wang |
| collection | DOAJ |
| description | ObjectiveAnxiety and depression-like symptoms occur in the early stages of Alzheimer’s disease. Hippocampal Sirtuin 1 (SIRT1) signaling mediates anxiety- and depression-like behavior. Exercise training improves anxiety and depression-like behavior in various disease models, such as the rat chronic restraint stress model, rat model of posttraumatic stress disorder, and rat model of fetal alcohol spectrum disorders. Here, we aimed to investigate whether exercise ameliorates anxiety- and depression like behaviors in APP/PS1 mice and explore the potential mechanisms.MethodsAfter eight weeks of exercise intervention, we assessed anxiety- and depression-like behaviors in Alzheimer’s disease (AD) model mice. We then measured the levels of SIRT1, peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC1α), nuclear respiratory factor 1 (NRF1), mitochondrial transcription factor A (TFAM), and mitochondrial biogenesis (CO2, ATP6, and mitochondrial content) using immunofluorescence, reverse transcription-quantitative real-time PCR, and transmission electron microscopy. Finally, we investigated the effects of pharmacological activation of SIRT1 on anxiety- and depression-like behaviors, the SIRT1/PGC-1α/NRF1/TFAM signaling axis, and mitochondrial biogenesis.ResultsWe first observed that treadmill exercise improved anxiety- and depression-like behaviors in six-month-old APP/PS1 mice and increased SIRT1 levels in the hippocampus. Pharmacological activation of hippocampal SIRT1 function also reduced anxiety and depression-like behaviors in APP/PS1 mice. Meanwhile, both treadmill exercise and pharmacological activation of hippocampal SIRT1 increased the levels of PGC1α, NRF1, TFAM, and enhanced mitochondrial biogenesis (CO2, ATP6, or mitochondrial content) in the hippocampus of APP/PS1 mice.ConclusionThese findings reveal that treadmill exercise reduces anxiety- and depression-like behaviors in six-month-old APP/PS1 mice by enhancing the SIRT1-dependent PGC-1α/NRF1/TFAM axis, promoting mitochondrial biogenesis in the hippocampus. |
| format | Article |
| id | doaj-art-7db28f5900904d58b7a3ea2f9332bca9 |
| institution | DOAJ |
| issn | 1663-4365 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Aging Neuroscience |
| spelling | doaj-art-7db28f5900904d58b7a3ea2f9332bca92025-08-20T02:49:01ZengFrontiers Media S.A.Frontiers in Aging Neuroscience1663-43652024-12-011610.3389/fnagi.2024.14892141489214Hippocampal SIRT1 signaling mediates the ameliorative effect of treadmill exercise on anxiety- and depression-like behavior in APP/PS1 miceYarong Wang0Yarong Wang1Rongxing Zhang2Yumin Jiang3Jingwen Liao4Jingwen Liao5Lianwei Mu6Lianwei Mu7Min Hu8Min Hu9Scientific Research Center, Guangzhou Sport University, Guangzhou, ChinaGuangdong Provincial Key Laboratory of Physical Activity and Health Promotion, Guangzhou Sport University, Guangzhou, ChinaScientific Research Center, Guangzhou Sport University, Guangzhou, ChinaScientific Research Center, Guangzhou Sport University, Guangzhou, ChinaScientific Research Center, Guangzhou Sport University, Guangzhou, ChinaGuangdong Provincial Key Laboratory of Physical Activity and Health Promotion, Guangzhou Sport University, Guangzhou, ChinaScientific Research Center, Guangzhou Sport University, Guangzhou, ChinaGuangdong Provincial Key Laboratory of Physical Activity and Health Promotion, Guangzhou Sport University, Guangzhou, ChinaScientific Research Center, Guangzhou Sport University, Guangzhou, ChinaGuangdong Provincial Key Laboratory of Physical Activity and Health Promotion, Guangzhou Sport University, Guangzhou, ChinaObjectiveAnxiety and depression-like symptoms occur in the early stages of Alzheimer’s disease. Hippocampal Sirtuin 1 (SIRT1) signaling mediates anxiety- and depression-like behavior. Exercise training improves anxiety and depression-like behavior in various disease models, such as the rat chronic restraint stress model, rat model of posttraumatic stress disorder, and rat model of fetal alcohol spectrum disorders. Here, we aimed to investigate whether exercise ameliorates anxiety- and depression like behaviors in APP/PS1 mice and explore the potential mechanisms.MethodsAfter eight weeks of exercise intervention, we assessed anxiety- and depression-like behaviors in Alzheimer’s disease (AD) model mice. We then measured the levels of SIRT1, peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC1α), nuclear respiratory factor 1 (NRF1), mitochondrial transcription factor A (TFAM), and mitochondrial biogenesis (CO2, ATP6, and mitochondrial content) using immunofluorescence, reverse transcription-quantitative real-time PCR, and transmission electron microscopy. Finally, we investigated the effects of pharmacological activation of SIRT1 on anxiety- and depression-like behaviors, the SIRT1/PGC-1α/NRF1/TFAM signaling axis, and mitochondrial biogenesis.ResultsWe first observed that treadmill exercise improved anxiety- and depression-like behaviors in six-month-old APP/PS1 mice and increased SIRT1 levels in the hippocampus. Pharmacological activation of hippocampal SIRT1 function also reduced anxiety and depression-like behaviors in APP/PS1 mice. Meanwhile, both treadmill exercise and pharmacological activation of hippocampal SIRT1 increased the levels of PGC1α, NRF1, TFAM, and enhanced mitochondrial biogenesis (CO2, ATP6, or mitochondrial content) in the hippocampus of APP/PS1 mice.ConclusionThese findings reveal that treadmill exercise reduces anxiety- and depression-like behaviors in six-month-old APP/PS1 mice by enhancing the SIRT1-dependent PGC-1α/NRF1/TFAM axis, promoting mitochondrial biogenesis in the hippocampus.https://www.frontiersin.org/articles/10.3389/fnagi.2024.1489214/fullSIRT1treadmill exerciseanxiety-and depression-like behaviorsmitochondrialAPP/PS1 mice |
| spellingShingle | Yarong Wang Yarong Wang Rongxing Zhang Yumin Jiang Jingwen Liao Jingwen Liao Lianwei Mu Lianwei Mu Min Hu Min Hu Hippocampal SIRT1 signaling mediates the ameliorative effect of treadmill exercise on anxiety- and depression-like behavior in APP/PS1 mice Frontiers in Aging Neuroscience SIRT1 treadmill exercise anxiety-and depression-like behaviors mitochondrial APP/PS1 mice |
| title | Hippocampal SIRT1 signaling mediates the ameliorative effect of treadmill exercise on anxiety- and depression-like behavior in APP/PS1 mice |
| title_full | Hippocampal SIRT1 signaling mediates the ameliorative effect of treadmill exercise on anxiety- and depression-like behavior in APP/PS1 mice |
| title_fullStr | Hippocampal SIRT1 signaling mediates the ameliorative effect of treadmill exercise on anxiety- and depression-like behavior in APP/PS1 mice |
| title_full_unstemmed | Hippocampal SIRT1 signaling mediates the ameliorative effect of treadmill exercise on anxiety- and depression-like behavior in APP/PS1 mice |
| title_short | Hippocampal SIRT1 signaling mediates the ameliorative effect of treadmill exercise on anxiety- and depression-like behavior in APP/PS1 mice |
| title_sort | hippocampal sirt1 signaling mediates the ameliorative effect of treadmill exercise on anxiety and depression like behavior in app ps1 mice |
| topic | SIRT1 treadmill exercise anxiety-and depression-like behaviors mitochondrial APP/PS1 mice |
| url | https://www.frontiersin.org/articles/10.3389/fnagi.2024.1489214/full |
| work_keys_str_mv | AT yarongwang hippocampalsirt1signalingmediatestheameliorativeeffectoftreadmillexerciseonanxietyanddepressionlikebehaviorinappps1mice AT yarongwang hippocampalsirt1signalingmediatestheameliorativeeffectoftreadmillexerciseonanxietyanddepressionlikebehaviorinappps1mice AT rongxingzhang hippocampalsirt1signalingmediatestheameliorativeeffectoftreadmillexerciseonanxietyanddepressionlikebehaviorinappps1mice AT yuminjiang hippocampalsirt1signalingmediatestheameliorativeeffectoftreadmillexerciseonanxietyanddepressionlikebehaviorinappps1mice AT jingwenliao hippocampalsirt1signalingmediatestheameliorativeeffectoftreadmillexerciseonanxietyanddepressionlikebehaviorinappps1mice AT jingwenliao hippocampalsirt1signalingmediatestheameliorativeeffectoftreadmillexerciseonanxietyanddepressionlikebehaviorinappps1mice AT lianweimu hippocampalsirt1signalingmediatestheameliorativeeffectoftreadmillexerciseonanxietyanddepressionlikebehaviorinappps1mice AT lianweimu hippocampalsirt1signalingmediatestheameliorativeeffectoftreadmillexerciseonanxietyanddepressionlikebehaviorinappps1mice AT minhu hippocampalsirt1signalingmediatestheameliorativeeffectoftreadmillexerciseonanxietyanddepressionlikebehaviorinappps1mice AT minhu hippocampalsirt1signalingmediatestheameliorativeeffectoftreadmillexerciseonanxietyanddepressionlikebehaviorinappps1mice |