浙江大学胡海岚研究团队报道了侧缰核神经元-星形胶质细胞偶联介导抑郁样行为。该研究于2025年4月24日发表于国际一流学术期刊《细胞》杂志上。

在自由运动小鼠的多脑区钙光度记录中，该课题组发现应激诱导星形细胞钙最快速的上升和LHb的双峰神经元反应。LHb星形细胞钙需要α 1A-肾上腺素能受体，并依赖于LHb和局部蓝蛋白（LC）之间的循环神经网络。LHb星形胶质细胞通过胶质递质谷氨酸和ATP/腺苷介导第二波LHb神经元激活和去甲肾上腺素（NE）释放。激活或抑制LHb星形细胞钙信号分别促进或阻止应激诱导的抑郁样行为。这些结果在LHb-LC轴上确定了应力诱导的正反馈回路，星形胶质细胞是一个关键的信号中继。这种突出的神经元-神经胶质相互作用的识别可能有助于压力管理和抑郁预防。

据了解，侧链（LHb）神经元和星形胶质细胞与抑郁症病因密切相关，但尚不清楚两者在抑郁症发病过程中如何动态相互作用。

附：英文原文

Title: Neuron-astrocyte coupling in lateral habenula mediates depressive-like behaviors

Author: Qianqian Xin, Junying Wang, Jinkun Zheng, Yi Tan, Xiaoning Jia, Zheyi Ni, Zijie Xu, Jiesi Feng, Zhaofa Wu, Yulong Li, Xiao-Ming Li, Huan Ma, Hailan Hu

Issue&Volume: 2025-04-24

Abstract: The lateral habenula (LHb) neurons and astrocytes have been strongly implicated in depression etiology, but it was not clear how the two dynamically interact during depression onset. Here, using multi-brain-region calcium photometry recording in freely moving mice, we discover that stress induces a most rapid astrocytic calcium rise and a bimodal neuronal response in the LHb. LHb astrocytic calcium requires the α1A-adrenergic receptor and depends on a recurrent neural network between the LHb and locus coeruleus (LC). Through the gliotransmitter glutamate and ATP/adenosine, LHb astrocytes mediate the second-wave LHb neuronal activation and norepinephrine (NE) release. Activation or inhibition of LHb astrocytic calcium signaling facilitates or prevents stress-induced depressive-like behaviors, respectively. These results identify a stress-induced positive feedback loop in the LHb-LC axis, with astrocytes being a critical signaling relay. The identification of this prominent neuron-glia interaction may shed light on stress management and depression prevention.

DOI: 10.1016/j.cell.2025.04.010

Source: https://www.cell.com/cell/abstract/S0092-8674(25)00411-8