Social interaction following prepubertal stress alters prefrontal gene expression associated with cell signalling and oligodendrocytes

Early-life adversity is associated with an increased risk of psychopathology, including mood disorders, later in life. Early-life stress affects several physiological systems, however, the exact mechanisms underlying pathological risk are not fully understood. This knowledge is crucial in developing appropriate therapeutic interventions. The prepubertal period is documented as a key developmental period for the maturation of the prefrontal cortex (PFC), a brain region involved in higher cognitive functions, including social function. In this study, we performed RNA sequencing on the PFC of adult rats who had experienced prepubertal stress (PPS) and controls to investigate the genome-wide consequences of this stress. PPS alters social behaviour in adulthood, therefore we also performed RNA sequencing on PPS and control rats following a social interaction test to determine social activity-dependent gene changes. At a baseline state (1 week following a social interaction test), no genes were differentially expressed in the PPS group. However, 1603 genes were differentially expressed in PPS rats compared to controls following a social interaction. These genes were enriched in biological pathways associated with cell signalling and axon myelination dynamics. Cell enrichment analysis showed these genes were associated with oligodendrocytes, and a comparison with an existing early-life stress sequencing dataset showed that pathways linked to oligodendrocyte morphology are impacted in a range of models of early-life stress in rodents. In conclusion, we identify pathways, including those involved in axon myelination, that are differentially activated in the adult in response to social stimulation following PPS. These differential responses may contribute to vulnerability to psychiatric pathology.

Automated summary

Early-life adversity increases the risk of developing psychopathology later in life, but the specific mechanisms are still not fully understood. In this study, RNA sequencing was performed on the prefrontal cortex of adult rats who experienced prepubertal stress (PPS) to investigate the genome-wide consequences of this stress. PPS altered social behavior in adulthood and was associated with differential gene expression related to cell signaling and axon myelination dynamics. These findings suggest that PPS-induced changes in gene pathways, including axon myelination, may contribute to vulnerability to psychiatric pathology.