Exercise‐Activated mPFC Tri‐Synaptic Pathway Ameliorates Depression‐Like Behaviors in Mouse
Abstract Exercise is considered as playing a pivotal role in the modulation of emotional responses. However, a precise circuit that mediates the effects of exercise on depression have yet to be elucidated. Here, a molecularly defined tri‐synaptic pathway circuit is identified that correlates motor i...
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| Format: | Article |
| Language: | English |
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Wiley
2025-01-01
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| Series: | Advanced Science |
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| Online Access: | https://doi.org/10.1002/advs.202408618 |
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| author | Tian Lan Ye Li Xiao Chen Wenjing Wang Changmin Wang Haiyan Lou Shihong Chen Shuyan Yu |
| author_facet | Tian Lan Ye Li Xiao Chen Wenjing Wang Changmin Wang Haiyan Lou Shihong Chen Shuyan Yu |
| author_sort | Tian Lan |
| collection | DOAJ |
| description | Abstract Exercise is considered as playing a pivotal role in the modulation of emotional responses. However, a precise circuit that mediates the effects of exercise on depression have yet to be elucidated. Here, a molecularly defined tri‐synaptic pathway circuit is identified that correlates motor inputs with antidepressant effects. With this pathway, initial inputs from neurons within the dorsal root ganglia (DRG) project to excitatory neurons in the gracile nucleus (GR), which in turn connect with 5‐HTergic neurons in the dorsal raphe nucleus (DRN), eventually coursing to excitatory pyramidal neurons within the medial prefrontal cortex (mPFC). Exercise activates this pathway, with the result that depressive‐ and anxiety‐like behaviors in mice are significantly reduced. In addition, it is found that exercise may exert antidepressant effects through regulating synaptic plasticity within this tri‐synaptic pathway. These findings reveal a hindbrain‐to‐forebrain neuronal circuit that specifically modulates depression and provides a potential mechanism for the antidepressant effects of exercise. |
| format | Article |
| id | doaj-art-2f368401f1604485978bc82ce406b363 |
| institution | Kabale University |
| issn | 2198-3844 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj-art-2f368401f1604485978bc82ce406b3632025-01-20T13:04:18ZengWileyAdvanced Science2198-38442025-01-01123n/an/a10.1002/advs.202408618Exercise‐Activated mPFC Tri‐Synaptic Pathway Ameliorates Depression‐Like Behaviors in MouseTian Lan0Ye Li1Xiao Chen2Wenjing Wang3Changmin Wang4Haiyan Lou5Shihong Chen6Shuyan Yu7Shandong Key Laboratory of Mental Disorders and Intelligent Control The Second Hospital of Shandong University School of Basic Medical Sciences Shandong University Jinan Shandong 250012 ChinaShandong Key Laboratory of Mental Disorders and Intelligent Control The Second Hospital of Shandong University School of Basic Medical Sciences Shandong University Jinan Shandong 250012 ChinaShandong Key Laboratory of Mental Disorders and Intelligent Control The Second Hospital of Shandong University School of Basic Medical Sciences Shandong University Jinan Shandong 250012 ChinaShandong Key Laboratory of Mental Disorders and Intelligent Control The Second Hospital of Shandong University School of Basic Medical Sciences Shandong University Jinan Shandong 250012 ChinaShandong Key Laboratory of Mental Disorders and Intelligent Control The Second Hospital of Shandong University School of Basic Medical Sciences Shandong University Jinan Shandong 250012 ChinaShandong Key Laboratory of Mental Disorders and Intelligent Control The Second Hospital of Shandong University School of Basic Medical Sciences Shandong University Jinan Shandong 250012 ChinaDepartment of Endocrinology and Metabolism The Second Hospital of Shandong University Jinan Shandong 250033 ChinaShandong Key Laboratory of Mental Disorders and Intelligent Control The Second Hospital of Shandong University School of Basic Medical Sciences Shandong University Jinan Shandong 250012 ChinaAbstract Exercise is considered as playing a pivotal role in the modulation of emotional responses. However, a precise circuit that mediates the effects of exercise on depression have yet to be elucidated. Here, a molecularly defined tri‐synaptic pathway circuit is identified that correlates motor inputs with antidepressant effects. With this pathway, initial inputs from neurons within the dorsal root ganglia (DRG) project to excitatory neurons in the gracile nucleus (GR), which in turn connect with 5‐HTergic neurons in the dorsal raphe nucleus (DRN), eventually coursing to excitatory pyramidal neurons within the medial prefrontal cortex (mPFC). Exercise activates this pathway, with the result that depressive‐ and anxiety‐like behaviors in mice are significantly reduced. In addition, it is found that exercise may exert antidepressant effects through regulating synaptic plasticity within this tri‐synaptic pathway. These findings reveal a hindbrain‐to‐forebrain neuronal circuit that specifically modulates depression and provides a potential mechanism for the antidepressant effects of exercise.https://doi.org/10.1002/advs.202408618depressiondorsal raphe nucleusexercisemedial prefrontal cortexsynaptic plasticity |
| spellingShingle | Tian Lan Ye Li Xiao Chen Wenjing Wang Changmin Wang Haiyan Lou Shihong Chen Shuyan Yu Exercise‐Activated mPFC Tri‐Synaptic Pathway Ameliorates Depression‐Like Behaviors in Mouse Advanced Science depression dorsal raphe nucleus exercise medial prefrontal cortex synaptic plasticity |
| title | Exercise‐Activated mPFC Tri‐Synaptic Pathway Ameliorates Depression‐Like Behaviors in Mouse |
| title_full | Exercise‐Activated mPFC Tri‐Synaptic Pathway Ameliorates Depression‐Like Behaviors in Mouse |
| title_fullStr | Exercise‐Activated mPFC Tri‐Synaptic Pathway Ameliorates Depression‐Like Behaviors in Mouse |
| title_full_unstemmed | Exercise‐Activated mPFC Tri‐Synaptic Pathway Ameliorates Depression‐Like Behaviors in Mouse |
| title_short | Exercise‐Activated mPFC Tri‐Synaptic Pathway Ameliorates Depression‐Like Behaviors in Mouse |
| title_sort | exercise activated mpfc tri synaptic pathway ameliorates depression like behaviors in mouse |
| topic | depression dorsal raphe nucleus exercise medial prefrontal cortex synaptic plasticity |
| url | https://doi.org/10.1002/advs.202408618 |
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