Chronic Social Defeat Alters Brain Vascular-Associated Cell Gene Expression Patterns Leading to Vascular Dysfunction and Immune System Activation

Authors

Joshua D Samuels
Madison L Lotstein
Michael L Lehmann
Abdel G Elkahloun
Subhadra Banerjee
Miles Herkenham

Publication Date

6-28-2023

Journal

Journal of Neuroinflammation

Abstract

Brain vascular integrity is critical for brain health, and its disruption is implicated in many brain pathologies, including psychiatric disorders. Brain-vascular barriers are a complex cellular landscape composed of endothelial, glial, mural, and immune cells. Yet currently, little is known about these brain vascular-associated cells (BVACs) in health and disease. Previously, we demonstrated that 14 days of chronic social defeat (CSD), a mouse paradigm that produces anxiety and depressive-like behaviors, causes cerebrovascular damage in the form of scattered microbleeds. Here, we developed a technique to isolate barrier-related cells from the mouse brain and subjected the isolated cells to single-cell RNA sequencing. Using this isolation technique, we found an enrichment in BVAC populations, including distinct subsets of endothelial and microglial cells. In CSD compared to non-stress, home-cage control, differential gene expression patterns disclosed biological pathways involving vascular dysfunction, vascular healing, and immune system activation. Overall, our work demonstrates a unique technique to study BVAC populations from fresh brain tissue and suggests that neurovascular dysfunction is a key driver of psychosocial stress-induced brain pathology.

Keywords

Animals, Mice, Social Defeat, Brain, Immune System, Blood-Brain Barrier, Gene Expression

Comments

Supplementary Materials

PMID: 37380974