近日，美国加州大学教授Baljit S. Khakh及其团队开发出杏仁核星形胶质细胞初级纤毛机制有助于应激行为。相关论文于2026年8月5日发表在《自然》杂志上。

本研究表明，杏仁核星形胶质细胞通过与其初级纤毛相关的信号机制参与应激相关行为。杏仁核星形胶质细胞在应激条件下在蛋白和基因表达水平上发生改变，显示出与初级纤毛相关的分子表达减少，初级纤毛在形态上较短。G 蛋白偶联受体（GPCR）是星形胶质细胞7和初级纤毛功能的核心。因此，该课题组研究人员推测GPCR信号激活可能对应激相关行为障碍有益。

课题组研究人员确定杏仁核星形细胞GPCR作为应激反应的调节因子。天然鞘鞘醇-1-磷酸受体1 (S1PR1) gpcr的化学遗传学和靶向性导致星形胶质细胞初级纤毛长度的恢复，纠正分子改变并改善应激相关行为。纤毛相关基因在人类杏仁核星形胶质细胞中大量表达，其中许多基因在应激相关脑疾病中表现出表达中断。S1PR1在人类组织的杏仁核星形胶质细胞中也高度表达。小鼠杏仁核星形胶质细胞原纤毛的选择性遗传破坏改变了星形胶质细胞和实质细胞的一些应激相关行为和基因表达。这些数据证实星形细胞纤毛在脑核中起重要作用。

总之，杏仁核星形胶质细胞和它们的初级纤毛在应激过程中被破坏，它们的恢复伴随着应激相关的分子和行为的改善。星形胶质细胞初级纤毛相关机制可能因此为应激相关和其他脑疾病提供新的治疗策略。

据了解，了解不良生活事件如何引发与压力相关的行为改变仍然是一个未解决的挑战。杏仁核是情绪和压力反应的组成部分，由星形胶质细胞、神经元和其他细胞组成。

附：英文原文

Title: Amygdala astrocyte primary cilium mechanisms contribute to stress behaviours

Author: Pelaz, Sara G., Mitsui, Katsukuni, Kolosowska, Natalia, Fritch, Haley, Neupane, Chiranjivi, Casha, Vanessa H., Alonso-Gardn, Marta, Pandey, Vijaya, Wang, Lizheng, Kawaguchi, Riki, Wohlschlegel, James A., Guo, Jiami, McCarroll, Steven A., Berretta, Sabina, Khakh, Baljit S.

Issue&Volume: 2026-08-05

Abstract: Understanding how adverse life events trigger stress-related behavioural changes remains an unresolved challenge. The amygdala is integral to emotion and stress responses1 and comprises astrocytes, neurons and other cells. Here we show that amygdala astrocytes contribute to stress-related behaviours through signalling mechanisms related to their primary cilia2. Amygdala astrocytes are altered during stress at the protein and gene expression level, display reduced expression of molecules related to primary cilia3,4 and have morphologically short primary cilia5,6. Gprotein-coupled receptors (GPCRs) are central to astrocyte7 and primary cilia2,8,9 function. Therefore, we speculated that GPCR signalling activation might be beneficial in stress-related behavioural disorders. We identified amygdala astrocyte GPCRs as regulators of responses following stress. Chemogenetics and targeting of native sphingosine-1-phosphate receptor 1 (S1PR1) GPCRs led to the restoration of astrocyte primary cilia length, corrected molecular alterations and improved stress-related behaviours. Cilium-related genes were abundantly expressed in human amygdala astrocytes, with many displaying disrupted expression in stress-related brain disorders. S1PR1 was also highly expressed in amygdala astrocytes from human tissue. Selective genetic disruption of amygdala astrocyte primary cilia in mice altered some stress-related behaviours and gene expression of astrocytes and parenchymal cells. These data confirm that astrocytic cilia have important roles in this brain nucleus. In summary, amygdala astrocytes and their primary cilia are disrupted during stress, and their restoration is accompanied by stress-related molecular and behavioural improvements. Astrocyte primary cilia-related mechanisms may therefore provide new treatment strategies for stress-related and other brain disorders.

DOI: 10.1038/s41586-026-10874-0

Source: https://www.nature.com/articles/s41586-026-10874-0