重庆医科大学谢鹏小组取得一项新突破。他们的研究显示，伏隔核的单核转录组学揭示了具有抑郁样行为的青春期猕猴细胞类型特异性失调。该项研究成果发表在2025年5月21日出版的《神经科学通报》上。

通过单核RNA测序，课题组研究人员发现了表现出抑郁样行为的青春期猕猴的伏隔核（NAc），特别是星形胶质细胞中细胞特异性转录组变化。抑郁猕猴神经元和神经胶质细胞中二酰基甘油激酶β水平显著降低，而神经胶质细胞中FKBP5水平升高。GABA能突触的破坏以及D-谷氨酰胺和D-谷氨酸代谢的破坏与中棘神经元（MSNs）和星形胶质细胞亚型的抑郁表型有关。星形胶质细胞与D1/D2-MSNs之间的通讯通路也被破坏，涉及骨形态发生蛋白-6和Erb-B2受体酪氨酸激酶-4等因素。大量转录组学和蛋白质组学分析证实了这些发现，并通过qRT-PCR、蛋白质印迹和免疫荧光在慢性不可预测的轻度应激大鼠和猕猴的NAc中证实了FKBP5上调。他们的研究结果强调了NAc中不同细胞类型在青少年抑郁症中的特定作用，为新的抗抑郁疗法提供了潜在的靶点。

据了解，青少年抑郁症越来越被认为是一种严重的精神健康障碍，具有独特的临床和分子特征。

附：英文原文

Title: Single-Nucleus Transcriptomics of the Nucleus Accumbens Reveals Cell-Type-Specific Dysregulation in Adolescent Macaques with Depressive-Like Behaviors

Author: Teng, Teng, Wu, Qingyuan, Yin, Bangmin, Zhang, Jushuang, Li, Xuemei, Zhang, Lige, Zhou, Xinyu, Xie, Peng

Issue&Volume: 2025-05-21

Abstract: Adolescent depression is increasingly recognized as a serious mental health disorder with distinct clinical and molecular features. Using single-nucleus RNA sequencing, we identified cell-specific transcriptomic changes in the nucleus accumbens (NAc), particularly in astrocytes, of adolescent macaques exhibiting depressive-like behaviors. The level of diacylglycerol kinase beta was significantly reduced in neurons and glial cells of depressed macaques, while FKBP5 levels increased in glial cells. Disruption of GABAergic synapses and disruption of D-glutamine and D-glutamate metabolism were linked to depressive phenotypes in medium spiny neurons (MSNs) and subtypes of astrocytes. Communication pathways between astrocytes and D1/D2-MSNs were also disrupted, involving factors like bone morphogenetic protein-6 and Erb-B2 receptor tyrosine kinase-4. Bulk transcriptomic and proteomic analyses corroborated these findings, and FKBP5 upregulation was confirmed by qRT-PCR, western blotting, and immunofluorescence in the NAc of rats and macaques with chronic unpredictable mild stress. Our results highlight the specific roles of different cell types in adolescent depression in the NAc, offering potential targets for new antidepressant therapies.

DOI: 10.1007/s12264-025-01412-5

Source: https://link.springer.com/article/10.1007/s12264-025-01412-5