Molecular adaptations of the blood–brain barrier promote stress resilience vs. depression

Significance Thirty to fifty percent of depressed individuals are unresponsive to commonly prescribed antidepressant treatments, suggesting that biological mechanisms, such as stress-induced inflammation and blood vessel dysfunction, remain untreated. The blood–brain barrier is the ultimate frontier between the brain and harmful toxins or inflammatory signals circulating in the blood. Depression and vulnerability to chronic social stress are associated with loss of this barrier integrity; however, the mechanisms involved remain poorly understood. Identification of adaptations leading to resilience under stressful conditions could help develop novel treatments. Here we combined behavioral, p…

Social Stress Induces Blood-Brain Barrier Leakiness and Molecular Alterations Promoting Depression or Stress Resilience

Sex differences in nucleus accumbens transcriptome profiles associated with susceptibility versus resilience to subchronic variable stress

Depression and anxiety disorders are more prevalent in females, but the majority of research in animal models, the first step in finding new treatments, has focused predominantly on males. Here we report that exposure to subchronic variable stress (SCVS) induces depression-associated behaviors in female mice, whereas males are resilient as they do not develop these behavioral abnormalities. In concert with these different behavioral responses, transcriptional analysis of nucleus accumbens (NAc), a major brain reward region, by use of RNA sequencing (RNA-seq) revealed markedly different patterns of stress regulation of gene expression between the sexes. Among the genes displaying sex differe…