Li Cai, Li Wentao, Wei Wenbin, Chen Qili, Gao Han, Zhao Yanqing, Zhang Lingling, Ling Li, Shen Hao, Shen Yifen, Shen Yihang
Department of Neurology, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200071, China.
Department of Oral Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, College of Stomatology, Shanghai Jiao Tong University; National Center for Stomatology; National Clinical Research Center for Oral Diseases; Shanghai Key Laboratory of Stomatology, Shanghai, 200013, China.
Mol Psychiatry. 2025 May;30(5):1995-2008. doi: 10.1038/s41380-024-02810-3. Epub 2024 Nov 9.
Post-stroke depression (PSD) is a common but severe mental complication after stroke. However, the cellular and molecular understanding of PSD is still yet to be illustrated. In current study, we prepared PSD rat model (MD) via unilateral middle cerebral artery occlusion (MCAO) and chronic stress stimulation (DEPR), and isolated hippocampal tissues for single cell sequencing of 10x Genomics Chromium. First, we determined the presence of the increased cell population of endothelium and microglia and the compromised oligodendrocytes in MD compared to NC, MCAO and DEPR. The enriched functions of highly variable genes (HVGs) of endothelium and microglia suggested a reinforced blood-brain barrier in MD. Next, cell clusters of endothelium, microglia and oligodendrocytes were individually analyzed, and the subtypes with distinct functions were identified. The presence of expression profiles, intercellular communications and signaling pathways of these three cell populations of PSD displayed a similar but more aggressive appearance with DEPR compared to MCAO and NC. Taken together, this study characterized the specific gene profile of endothelium, microglia and oligodendrocytes of hippocampal PSD by single cell sequencing, emphasizing the crosstalk among them to provide theoretical basis for the in-depth mechanism research and drug therapy of PSD.
中风后抑郁(PSD)是中风后常见但严重的精神并发症。然而,对PSD的细胞和分子层面的理解仍有待阐明。在本研究中,我们通过单侧大脑中动脉闭塞(MCAO)和慢性应激刺激(DEPR)制备了PSD大鼠模型(MD),并分离海马组织用于10x Genomics Chromium单细胞测序。首先,我们确定与NC、MCAO和DEPR相比,MD中内皮细胞和小胶质细胞的细胞群体增加,少突胶质细胞受损。内皮细胞和小胶质细胞的高变基因(HVG)的富集功能表明MD中血脑屏障增强。接下来,分别分析了内皮细胞、小胶质细胞和少突胶质细胞的细胞簇,并鉴定了具有不同功能的亚型。与MCAO和NC相比,PSD这三种细胞群体的表达谱、细胞间通讯和信号通路的存在与DEPR表现出相似但更具侵袭性的特征。综上所述,本研究通过单细胞测序对海马PSD的内皮细胞、小胶质细胞和少突胶质细胞的特定基因谱进行了表征,强调了它们之间的相互作用,为PSD的深入机制研究和药物治疗提供了理论依据。