Yang Jiajun, Jia Yifei, Guo Ting, Zhang Siqi, Huang Jin, Lu Huiling, Li Leyi, Xu Jiahao, Liu Gefei, Xiao Ke
The Brain Cognition and Brain Disease Institute, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China.
State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan 430070, China.
Int J Mol Sci. 2025 Jun 24;26(13):6063. doi: 10.3390/ijms26136063.
Organisms respond to environmental stress primarily through the autonomic nervous system and hypothalamic-pituitary-adrenal (HPA) axis, regulating metabolism, psychological states, and immune function and modulating memory, reward processing, and immune responses. The HPA axis plays a central role in stress response, exhibiting distinct activation patterns under acute versus chronic social defeat stress. However, differences in physiological impacts and regulatory pathways between these stress conditions remain understudied. This study integrates RNA sequencing and behavioral analyses to reveal that acute social defeat stress triggers transient anxiety-like behaviors, accompanied by systemic inflammation and immediate-early gene (IEG) activation. In contrast, chronic social defeat stress induces long-term behavioral and physiological alterations, including neurotransmitter imbalance (e.g., reduced GABA and increased glutamate), sustained activation of maladaptive pathways (e.g., IL-17 signaling), and disrupted corticosterone synthesis. These findings highlight the dynamic regulatory role of the HPA axis under varying stress conditions, providing novel insights into mental health disorders such as anxiety and depression. The study identifies potential therapeutic targets to mitigate chronic social defeat stress effects and offers a theoretical foundation for personalized interventions.
生物体主要通过自主神经系统和下丘脑-垂体-肾上腺（HPA）轴对环境应激作出反应，调节新陈代谢、心理状态和免疫功能，并调节记忆、奖赏处理和免疫反应。HPA轴在应激反应中起核心作用，在急性与慢性社会挫败应激下表现出不同的激活模式。然而，这些应激条件下生理影响和调节途径的差异仍未得到充分研究。本研究整合RNA测序和行为分析，以揭示急性社会挫败应激引发短暂的焦虑样行为，伴有全身炎症和即刻早期基因（IEG）激活。相比之下，慢性社会挫败应激会导致长期的行为和生理改变，包括神经递质失衡（如γ-氨基丁酸减少和谷氨酸增加）、适应不良途径的持续激活（如白细胞介素-17信号传导）以及皮质酮合成紊乱。这些发现突出了HPA轴在不同应激条件下的动态调节作用，为焦虑和抑郁等心理健康障碍提供了新的见解。该研究确定了减轻慢性社会挫败应激影响的潜在治疗靶点，并为个性化干预提供了理论基础。
