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

Abstract

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.

Abstract

In this study, Wang et al. explored the potential pathogenesis of chronic social defeat stress (CSDS)‐induced depressive‐like behaviour in mice using 10× Visium spatial transcriptomics (ST) technique. Many of the depression‐related gene changes were identified and more pronounced in the hippocampus (HIP), cortex (Isocortex), and amygdala (AMY) in susceptible (SUS) mice compared to control and resilient (RES) mice. In particular, compared to other cell types, inhibitory interneurons, and synaptic function were most significantly affected in multiple brain regions following CSDS.