重庆医科大学谢鹏课题组取得一项新突破。他们揭示了海马体中的IL-17A通过抑制性突触传递调节绝望样行为。相关论文于2026年3月17日发表于国际顶尖学术期刊《中国药理学报》杂志上。

神经炎症在抑郁症的病理生理中起着重要作用。白细胞介素-17A（IL-17A）是一种炎症细胞因子，与抑郁症密切相关；然而，大脑中IL-17A调节抑郁症状的潜在机制尚不清楚。他们的研究旨在找出大脑中IL-17A调节抑郁样行为的潜在途径。抗绝望样行为是评价小鼠抑郁的重要指标，IL-17A基因敲除小鼠存在抗绝望样行为。考虑到海马体是一个与抑郁有关的大脑区域，该研究组在慢性不可预测的轻度应激（CUMS）小鼠中评估了海马体中IL-17A的水平，结果显示海马体中IL-17A水平升高。随后，通过立体定向注射装载IL-17A重组蛋白的多泡脂质体作为持续释放系统，并将AAV-il17a或AAV-shRNA（il17a）注入海马，调节IL-17A的表达。IL-17A过表达可诱导绝望样行为，IL-17A敲除小鼠海马区IL-17A表达的恢复可阻断抗绝望样表型，证实IL-17A在抑郁中的作用。基因芯片，UPLCMS/MS、Western blot和膜片钳分析确定IL-17A调控绝望样行为的途径。il - 17a敲除小鼠抑制性突触传递增强。

此外，降低GABAA受体α2亚基（GABRA2）的表达可消除IL-17A敲除小鼠的抗绝望样行为，海马GABARA2过表达可减轻CUMS小鼠的绝望样行为。这些结果证明，GABRA2介导的抑制性突触传递参与了IL-17A对抑郁样行为的调节。他们的研究结果揭示了IL-17A在抑郁症中的重要作用，并表明GABRA2是参与IL-17A调节抑郁症的关键分子，这表明它有可能成为抑郁症的治疗靶点。

附：英文原文

Title: IL-17A in the hippocampus regulates despair-like behaviors via inhibitory synaptic transmission

Author: Wang, Yue, Yu, He-ming, He, Yong, Cai, Jun-chao, Tian, Yu, Chen, Xiang-yu, Wu, Qing-yuan, Yuan, Ti-fei, Xie, An-mu, Guo, Yi, Cheng, Ke, Xie, Peng

Issue&Volume: 2026-03-17

Abstract: Neuroinflammation plays an important role in the pathophysiology of depression. Interleukin-17A (IL-17A), an inflammatory cytokine, is strongly associated with depression; however, the potential mechanisms through which IL-17A in the brain regulates depressive symptoms remain unknown. Our study aimed at finding out the potential pathway through which IL-17A in the brain regulates depressive-like behaviours. Anti-despair-like behaviours, an important index for evaluating depression in mice, are present in IL-17A knockout mice. Given that the hippocampus is a brain region that is implicated in depression, the level of IL-17A in the hippocampus was evaluated in chronic unpredictable mild stress (CUMS) mice, and the results revealed increased hippocampal IL-17A levels. The expression of IL-17A was subsequently regulated by the stereotactic injection of multivesicular liposomes loaded with IL-17A recombinant protein as a sustained release system, and the AAV-il17a or AAV-shRNA(il17a) into the hippocampus. IL-17A overexpression induced despair-like behaviour, and the anti-despair-like phenotype in IL-17A knockout mice was blocked by the restoration of IL-17A expression in the hippocampus, which demonstrated the role of IL-17A in depression. Gene microarray, UPLCMS/MS, Western blot and patch clamp analyses were used to determine the pathway through which IL-17A regulates despair-like behaviours. Enhanced inhibitory synaptic transmission was detected in IL-17A-knockout mice. Furthermore, reducing the expression of the GABAA receptor α2 subunit (GABRA2) abrogated antidespair-like behaviour in IL-17A knockout mice, and hippocampal GABARA2 overexpression alleviated despair-like behaviour in CUMS mice. These results proved that GABRA2-mediated inhibitory synaptic transmission participated in the regulation of depressive-like behaviours by IL-17A. Our results revealed a vital role for IL-17A in depression and suggested that GABRA2 is the key molecule involved in the regulation of depression by IL-17A, indicating its potential as a therapeutic target for depression.

DOI: 10.1038/s41401-026-01761-5

Source: https://www.nature.com/articles/s41401-026-01761-5