Stress-induced GHS-R1a expression in medial prefrontal cortical neurons promotes vulnerability to anxiety in mice
Abstract The neural basis of anxiety is unclear, which hinders the treatment of anxiety disorders. Here, we found that αCaMKII+ neurons in the medial prefrontal cortex (mPFCαCaMKII+) responded to stressors with increased activity both under physiological conditions and after repeated restraint stres...
Saved in:
| Main Authors: | , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2025-03-01
|
| Series: | Communications Biology |
| Online Access: | https://doi.org/10.1038/s42003-025-07802-9 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849311036580036608 |
|---|---|
| author | Liu Yang Meng Zhang Xiaomin Sun Anqi Du Jiajia Jia Nan Li Gonghui Hu Yingchang Lu Sihan Wang Jingsai Zhang Wenjie Chen Hanbing Yu Yu Zhou |
| author_facet | Liu Yang Meng Zhang Xiaomin Sun Anqi Du Jiajia Jia Nan Li Gonghui Hu Yingchang Lu Sihan Wang Jingsai Zhang Wenjie Chen Hanbing Yu Yu Zhou |
| author_sort | Liu Yang |
| collection | DOAJ |
| description | Abstract The neural basis of anxiety is unclear, which hinders the treatment of anxiety disorders. Here, we found that αCaMKII+ neurons in the medial prefrontal cortex (mPFCαCaMKII+) responded to stressors with increased activity both under physiological conditions and after repeated restraint stress (RRS) in mice. Chemogenetic activation of mPFCαCaMKII+ neurons ameliorated stress-induced anxiety. A delayed increase in the expression of growth hormone secretagogue receptor 1a (GHS-R1a), the receptor of the peripheral metabolic hormone ghrelin, in mPFCαCaMKII+ neurons coincided with reduced excitatory synaptic transmission and the development of RRS-induced enhancement of anxiety-related behavior. Virus-mediated GHS-R1a upregulation in mPFCαCaMKII+ neurons exaggerated the excitation/inhibition (E/I) imbalance and promoted anxiety-related behavior, whereas GHS-R1a knockdown had the opposite effect. We conclude that GHS-R1a signaling contributes to the development of stress-induced anxiety by shaping synaptic activity of mPFCαCaMKII+ neurons. GHS-R1a may be a new therapeutic target for treating anxiety disorders. |
| format | Article |
| id | doaj-art-88e247e7d6c245709367fa5148b42fc0 |
| institution | Kabale University |
| issn | 2399-3642 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Communications Biology |
| spelling | doaj-art-88e247e7d6c245709367fa5148b42fc02025-08-20T03:53:32ZengNature PortfolioCommunications Biology2399-36422025-03-018111210.1038/s42003-025-07802-9Stress-induced GHS-R1a expression in medial prefrontal cortical neurons promotes vulnerability to anxiety in miceLiu Yang0Meng Zhang1Xiaomin Sun2Anqi Du3Jiajia Jia4Nan Li5Gonghui Hu6Yingchang Lu7Sihan Wang8Jingsai Zhang9Wenjie Chen10Hanbing Yu11Yu Zhou12Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Qingdao UniversityDepartment of Physiology and Pathophysiology, School of Basic Medical Sciences, Qingdao UniversityDepartment of Physiology and Pathophysiology, School of Basic Medical Sciences, Qingdao UniversityDepartment of Physiology and Pathophysiology, School of Basic Medical Sciences, Qingdao UniversityDepartment of Physiology and Pathophysiology, School of Basic Medical Sciences, Qingdao UniversityDepartment of Health and Life Sciences, University of Health and Rehabilitation SciencesDepartment of Physiology and Pathophysiology, School of Basic Medical Sciences, Qingdao UniversityDepartment of Physiology and Pathophysiology, School of Basic Medical Sciences, Qingdao UniversityDepartment of Physiology and Pathophysiology, School of Basic Medical Sciences, Qingdao UniversityDepartment of Physiology and Pathophysiology, School of Basic Medical Sciences, Qingdao UniversityDepartment of Physiology and Pathophysiology, School of Basic Medical Sciences, Qingdao UniversityDepartment of Physiology and Pathophysiology, School of Basic Medical Sciences, Qingdao UniversityDepartment of Physiology and Pathophysiology, School of Basic Medical Sciences, Qingdao UniversityAbstract The neural basis of anxiety is unclear, which hinders the treatment of anxiety disorders. Here, we found that αCaMKII+ neurons in the medial prefrontal cortex (mPFCαCaMKII+) responded to stressors with increased activity both under physiological conditions and after repeated restraint stress (RRS) in mice. Chemogenetic activation of mPFCαCaMKII+ neurons ameliorated stress-induced anxiety. A delayed increase in the expression of growth hormone secretagogue receptor 1a (GHS-R1a), the receptor of the peripheral metabolic hormone ghrelin, in mPFCαCaMKII+ neurons coincided with reduced excitatory synaptic transmission and the development of RRS-induced enhancement of anxiety-related behavior. Virus-mediated GHS-R1a upregulation in mPFCαCaMKII+ neurons exaggerated the excitation/inhibition (E/I) imbalance and promoted anxiety-related behavior, whereas GHS-R1a knockdown had the opposite effect. We conclude that GHS-R1a signaling contributes to the development of stress-induced anxiety by shaping synaptic activity of mPFCαCaMKII+ neurons. GHS-R1a may be a new therapeutic target for treating anxiety disorders.https://doi.org/10.1038/s42003-025-07802-9 |
| spellingShingle | Liu Yang Meng Zhang Xiaomin Sun Anqi Du Jiajia Jia Nan Li Gonghui Hu Yingchang Lu Sihan Wang Jingsai Zhang Wenjie Chen Hanbing Yu Yu Zhou Stress-induced GHS-R1a expression in medial prefrontal cortical neurons promotes vulnerability to anxiety in mice Communications Biology |
| title | Stress-induced GHS-R1a expression in medial prefrontal cortical neurons promotes vulnerability to anxiety in mice |
| title_full | Stress-induced GHS-R1a expression in medial prefrontal cortical neurons promotes vulnerability to anxiety in mice |
| title_fullStr | Stress-induced GHS-R1a expression in medial prefrontal cortical neurons promotes vulnerability to anxiety in mice |
| title_full_unstemmed | Stress-induced GHS-R1a expression in medial prefrontal cortical neurons promotes vulnerability to anxiety in mice |
| title_short | Stress-induced GHS-R1a expression in medial prefrontal cortical neurons promotes vulnerability to anxiety in mice |
| title_sort | stress induced ghs r1a expression in medial prefrontal cortical neurons promotes vulnerability to anxiety in mice |
| url | https://doi.org/10.1038/s42003-025-07802-9 |
| work_keys_str_mv | AT liuyang stressinducedghsr1aexpressioninmedialprefrontalcorticalneuronspromotesvulnerabilitytoanxietyinmice AT mengzhang stressinducedghsr1aexpressioninmedialprefrontalcorticalneuronspromotesvulnerabilitytoanxietyinmice AT xiaominsun stressinducedghsr1aexpressioninmedialprefrontalcorticalneuronspromotesvulnerabilitytoanxietyinmice AT anqidu stressinducedghsr1aexpressioninmedialprefrontalcorticalneuronspromotesvulnerabilitytoanxietyinmice AT jiajiajia stressinducedghsr1aexpressioninmedialprefrontalcorticalneuronspromotesvulnerabilitytoanxietyinmice AT nanli stressinducedghsr1aexpressioninmedialprefrontalcorticalneuronspromotesvulnerabilitytoanxietyinmice AT gonghuihu stressinducedghsr1aexpressioninmedialprefrontalcorticalneuronspromotesvulnerabilitytoanxietyinmice AT yingchanglu stressinducedghsr1aexpressioninmedialprefrontalcorticalneuronspromotesvulnerabilitytoanxietyinmice AT sihanwang stressinducedghsr1aexpressioninmedialprefrontalcorticalneuronspromotesvulnerabilitytoanxietyinmice AT jingsaizhang stressinducedghsr1aexpressioninmedialprefrontalcorticalneuronspromotesvulnerabilitytoanxietyinmice AT wenjiechen stressinducedghsr1aexpressioninmedialprefrontalcorticalneuronspromotesvulnerabilitytoanxietyinmice AT hanbingyu stressinducedghsr1aexpressioninmedialprefrontalcorticalneuronspromotesvulnerabilitytoanxietyinmice AT yuzhou stressinducedghsr1aexpressioninmedialprefrontalcorticalneuronspromotesvulnerabilitytoanxietyinmice |