前额叶促肾上腺皮质激素释放因子促进对社会压力的适应能力。

Ya-Tao Wang, Yong Li, Meng-Yun Li, Yue-Ming Zhang, Yue Wang, Qi-Qi Xu, Rong-Yu Liu, Xin-Ya Qin, Qing-Hong Shan, Yu Wang, Jiang-Ning Zhou, Peng Chen
{"title":"前额叶促肾上腺皮质激素释放因子促进对社会压力的适应能力。","authors":"Ya-Tao Wang, Yong Li, Meng-Yun Li, Yue-Ming Zhang, Yue Wang, Qi-Qi Xu, Rong-Yu Liu, Xin-Ya Qin, Qing-Hong Shan, Yu Wang, Jiang-Ning Zhou, Peng Chen","doi":"10.1038/s41386-025-02148-6","DOIUrl":null,"url":null,"abstract":"<p><p>Variations in individual coping styles have been linked to either resilience or vulnerability towards stress, thereby influencing the probability of developing stress-related disorders. The involvement of corticotropin-releasing factor (CRF) neurons within the medial prefrontal cortex (mPFC) plays a crucial role in modulating behavioral responses to stressful situations. In this study utilizing a mouse model of social defeat stress (SDS), we demonstrate how coordinated activation and localized release of CRF within the mPFC contribute to promoting adaptive responses under stressful conditions leading to enhanced resilience against subsequent challenges. Specifically, during SDS exposure, heightened activity levels were observed among mPFC CRF neurons coincide with increased local release triggered by active exploration and defensive behaviors, while decreased responses were detected upon exposure to aggression. Interestingly, the CRF neural activity and local release responding to coping behaviors throughout chronic social defeat stress (CSDS) differed between susceptible and resilient mice. Furthermore, activation of CRF receptor 1 (CRFR1) signaling in the mPFC enhanced active coping behaviors and conferred resilience to CSDS, while inhibition of CRF system promoted passive coping behaviors and induced susceptibility to sub-threshold SDS. Additionally, inhibition of CRFR1 in the mPFC nullified the pro-resilience effect elicited by activation of CRF neurons during CSDS. The collective findings provide evidence supporting the crucial role of local endogenous CRF derived from mPFC CRF neurons in maintaining resilience through active coping styles when confronted with social stress. Moreover, these results suggest that targeting the mPFC CRF system could hold promise as a therapeutic approach for managing stress-related disorders.</p>","PeriodicalId":520722,"journal":{"name":"Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology","volume":" ","pages":""},"PeriodicalIF":0.0000,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Prefrontal corticotropin-releasing factor promotes resilience to social stress.\",\"authors\":\"Ya-Tao Wang, Yong Li, Meng-Yun Li, Yue-Ming Zhang, Yue Wang, Qi-Qi Xu, Rong-Yu Liu, Xin-Ya Qin, Qing-Hong Shan, Yu Wang, Jiang-Ning Zhou, Peng Chen\",\"doi\":\"10.1038/s41386-025-02148-6\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Variations in individual coping styles have been linked to either resilience or vulnerability towards stress, thereby influencing the probability of developing stress-related disorders. The involvement of corticotropin-releasing factor (CRF) neurons within the medial prefrontal cortex (mPFC) plays a crucial role in modulating behavioral responses to stressful situations. In this study utilizing a mouse model of social defeat stress (SDS), we demonstrate how coordinated activation and localized release of CRF within the mPFC contribute to promoting adaptive responses under stressful conditions leading to enhanced resilience against subsequent challenges. Specifically, during SDS exposure, heightened activity levels were observed among mPFC CRF neurons coincide with increased local release triggered by active exploration and defensive behaviors, while decreased responses were detected upon exposure to aggression. Interestingly, the CRF neural activity and local release responding to coping behaviors throughout chronic social defeat stress (CSDS) differed between susceptible and resilient mice. Furthermore, activation of CRF receptor 1 (CRFR1) signaling in the mPFC enhanced active coping behaviors and conferred resilience to CSDS, while inhibition of CRF system promoted passive coping behaviors and induced susceptibility to sub-threshold SDS. Additionally, inhibition of CRFR1 in the mPFC nullified the pro-resilience effect elicited by activation of CRF neurons during CSDS. The collective findings provide evidence supporting the crucial role of local endogenous CRF derived from mPFC CRF neurons in maintaining resilience through active coping styles when confronted with social stress. Moreover, these results suggest that targeting the mPFC CRF system could hold promise as a therapeutic approach for managing stress-related disorders.</p>\",\"PeriodicalId\":520722,\"journal\":{\"name\":\"Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2025-06-10\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1038/s41386-025-02148-6\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1038/s41386-025-02148-6","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0

摘要

个人应对方式的差异与对压力的复原力或脆弱性有关,从而影响发展与压力有关的疾病的可能性。内侧前额叶皮层(mPFC)中的促肾上腺皮质激素释放因子(CRF)神经元在调节应激情境下的行为反应中起着至关重要的作用。本研究利用小鼠社会失败应激(SDS)模型,展示了mPFC中CRF的协调激活和局部释放如何促进应激条件下的适应性反应,从而增强对后续挑战的恢复力。具体而言,在SDS暴露期间,mPFC CRF神经元的活动水平升高与主动探索和防御行为引发的局部释放增加相一致,而暴露于攻击时则检测到反应降低。有趣的是,在慢性社会失败应激(CSDS)中,易感小鼠和弹性小鼠对应对行为的CRF神经活动和局部释放有所不同。此外,mPFC中CRF受体1 (CRFR1)信号的激活增强了主动应对行为并赋予了对CSDS的恢复力,而CRF系统的抑制促进了被动应对行为并诱导了对亚阈值SDS的易感性。此外,mPFC中CRFR1的抑制抵消了CSDS期间CRF神经元激活所引发的促恢复效应。这些研究结果提供了证据,支持来自mPFC CRF神经元的局部内源性CRF在面对社会压力时通过积极应对方式维持弹性方面的关键作用。此外,这些结果表明,靶向mPFC CRF系统可能有望成为治疗压力相关疾病的治疗方法。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Prefrontal corticotropin-releasing factor promotes resilience to social stress.

Variations in individual coping styles have been linked to either resilience or vulnerability towards stress, thereby influencing the probability of developing stress-related disorders. The involvement of corticotropin-releasing factor (CRF) neurons within the medial prefrontal cortex (mPFC) plays a crucial role in modulating behavioral responses to stressful situations. In this study utilizing a mouse model of social defeat stress (SDS), we demonstrate how coordinated activation and localized release of CRF within the mPFC contribute to promoting adaptive responses under stressful conditions leading to enhanced resilience against subsequent challenges. Specifically, during SDS exposure, heightened activity levels were observed among mPFC CRF neurons coincide with increased local release triggered by active exploration and defensive behaviors, while decreased responses were detected upon exposure to aggression. Interestingly, the CRF neural activity and local release responding to coping behaviors throughout chronic social defeat stress (CSDS) differed between susceptible and resilient mice. Furthermore, activation of CRF receptor 1 (CRFR1) signaling in the mPFC enhanced active coping behaviors and conferred resilience to CSDS, while inhibition of CRF system promoted passive coping behaviors and induced susceptibility to sub-threshold SDS. Additionally, inhibition of CRFR1 in the mPFC nullified the pro-resilience effect elicited by activation of CRF neurons during CSDS. The collective findings provide evidence supporting the crucial role of local endogenous CRF derived from mPFC CRF neurons in maintaining resilience through active coping styles when confronted with social stress. Moreover, these results suggest that targeting the mPFC CRF system could hold promise as a therapeutic approach for managing stress-related disorders.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
自引率
0.00%
发文量
0
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:604180095
Book学术官方微信