Exploring sex-dependent effects of social deprivation during early adolescence

Recent evidence suggests that early life adverse events, such as social isolation during childhood and adolescence, may trigger immune system response and contribute to mental health problems. We hypothesize that short-term social isolation in early life leaves a lasting immune imprint in the brain that may, in turn, influence vulnerability to psychiatric diseases later in life in a sex-specific manner. Adolescent male and female Wistar rats were assigned to group-housed (GH) or social isolation (SI) group. SI lasted 7 days from postnatal day (PND)28 to 35, followed by re-grouping. Sixty-minutes open field (OF) and 48-h sucrose preference (SP) tests were conducted at PND40-43. Animals were sacrificed at PND60. Gene expression was investigated in the amygdala (Amy), dorsal (dH) and ventral (vH) hippocampus. SI led to a significant increase in OF locomotor activity and greater sucrose preference in the first 24 hours of the SP test independently of sex. At the molecular level we evaluated a panel of gene related to microglia. SI in females increased Trem2 and decreased Cd11b, Cd86 and P2yr12 gene expression levels in Amy; increased Cx3cl1 and reduced Cd68, Cx3cr1 in dH; and decreased Trem2 in vH. Differently, SI male rats showed decreased Trem2, Cd68, Cd11b, and Cd86 mRNA levels in Amy; decreased levels of Trem2, P2yr12, and Cx3cr1 in dH; and increased Iba1 and P2yr12 in vH compared to the same sex GH group. In conclusion, even though SI induced a similar behavioral profile in both females and males, the microglia transcriptional profile was altered in a sex-dependent manner across different brain regions.