Exploration｜慢性社交挫败应激（CSDS）小鼠大脑空间转录组学分析

Spatial transcriptomic analysis of the mouse brain following chronic social defeat stress

该论文插图由格索普生物制图团队创作

抑郁症是一种非常普遍的致残性精神障碍，涉及许多与大脑多个区域异常功能相关的基因变化。然而，很少有慢性社会失败应激（CSDS）的转录组学特征来全面比较多个大脑区域的转录变化。空间转录组学（ST）用于揭示对照、弹性（RES）和易感（SUS）小鼠大脑中基因表达的空间差异，并注释了8个解剖大脑区域和6种细胞类型。基因表达谱揭示了CSDS导致不同大脑区域的基因同步变化。随后发现CSDS主要影响多个区域的抑制性神经元和突触功能。大脑区域海马（HIP）、等皮层和杏仁核（AMY）在与抑郁性精神障碍相关的基因中表现出比其他区域更明显的转录变化。这三个大脑区域之间的信号交流可能在CSDS易感性中发挥关键作用。总之，这项研究为ST水平的CSDS易感性提供了重要的新见解，为理解和治疗抑郁症提供了一种新的方法。

Depression is a highly prevalent and disabling mental disorder, involving numerous genetic changes that are associated with abnormal functions in multiple regions of the brain. However, there is little transcriptomic-wide characterization of chronic social defeat stress (CSDS) to comprehensively compare the transcriptional changes in multiple brain regions. Spatial transcriptomics (ST) was used to reveal the spatial difference of gene expression in the control, resilient (RES) and susceptible (SUS) mouse brains, and annotated eight anatomical brain regions and six cell types. The gene expression profiles uncovered that CSDS leads to gene synchrony changes in different brain regions. Then it was identified that inhibitory neurons and synaptic functions in multiple regions were primarily affected by CSDS. The brain regions Hippocampus (HIP), Isocortex, and Amygdala (AMY) present more pronounced transcriptional changes in genes associated with depressive psychiatric disorders than other regions. Signalling communication between these three brain regions may play a critical role in susceptibility to CSDS. Taken together, this study provides important new insights into CSDS susceptibility at the ST level, which offers a new approach for understanding and treating depression.