Transcriptional profiling of astrocytes in the prefrontal cortex, hippocampus, accumbens nucleus and caudate putamen of a Aldh1l1-TRAP (JD130) mouse line after chronic social defeat stress

Psychiatric disorders, especially major depressive disorder, are prominent cause of disability worldwide, and in dire need of better diagnostic and therapeutic tools. In order to identify the cellular mechanisms underlying major depressive disorder we sought to understand the role of astrocytes, the most numerous subtype of glia, in this disease utilizing the TRAP gene expression analysis and chronic social defeat mouse model of depression. TRAP translational profiling is a method that allows investigators to genetically characterize specific cell types in complex tissues such as mouse brain. Using this technique we obtained RNA-Seq data from actively translating transcripts present in astrocytes. We generated the molecular profile of astrocytes from multiple brain regions affected by stress-induced depression, the prefrontal cortex, hippocampus, accumbens nucleus and caudate putamen of adult Aldh1l1-EGFP/Rpl10a (JD130) mice after chronic social defeat stress paradigm. The results of this study will further our understanding of depression pathophysiology and will provide possible targets for novel or supplementary therapies. Adult Aldh1l1-EGFP/Rpl10a (JD130) mice were subjected to 10 days of social defeat and screened for social interaction (SI). They were divided in three groups based on their SI index: control-CTRL (no stress exposure, but present in the same environment-room, SI>1), resilient-RS (exposed to stress but showing no depressive-like symptoms, SI >1) and stress susceptible-SS (showing low social interaction index as a measure of depressive-like symptoms, SI<1). Two days after the last day of social defeat TRAP-Seq of astrocytes isolated from the prefrontal cortex (PFC), hippocampus (HIP), accumbens nucleus (NAC) and caudate putamen (CPU) was performed. Each biological replicate sample contained pooled regions isolated from 2 (for PFC, HIP and CPU) or 4-6 (for NAC) mice. The bioinformatics analysis was done comparing gene expression datasets from CTRL, RS, and SS mice. Genes showing significant change in expression in SS compared to RS and CTRL were further analyzed.