Genomic changes in response to different doses of early life stress in the developing hippocampus

Early adversity in the form of neglect, abuse, and unpredictable stress impairs hippocampal development across diverse mammalian species. Individuals exposed to multiple adversities are more impacted compared to those exposed to a single adversity. However, the mechanisms responsible for this dose-dependent effect are unclear and have not been investigated in animal models. Here we assess the effects of a single stressor (i.e. limited bedding/nesting) abbreviated as LB and unpredictable multiple stressors (limited bedding/nesting, unpredictable maternal separation, and nest disruption) abbreviated as UPS on gene expression in the hippocampus of 17-day old pups (P17). Overall design: RNA was isolated from the left hippocampus of 17-day old pups raised under control (CTL), limited bedding (LB), or unpredictable postnatal stress (UPS) and sequenced using the Illumina NovaSeq 6000 at an average depth of 73MR per sample. Reads were trimmed, aligned, and gene expression in TPM was calculated using HISAT2. TPM for all samples are shown in the processed data file: ELS_Sex_exp49.txt (TPMS). Low expressing gene (TPM < 3 in all three groups) were removed and the remaining 13,245 genes were analyzed using DESeq2 script in R (Love et al., 2014) to identify genes that are differentially expressed between the three groups. The information is provided in one excel file (Summary DRG 050322) containing CTL_LB, CTL_UPS, and LB_UPS comparisons. Each comparison provides info for gene name, log2 fold change, p-value, and padj (correcting for false discovery rate using Benjamin and Hochberg correction).