The effect of social isolation on rat behavior and expression of genes related to neuroinflammation depends on sex.

It is known that isolation in social animal species leads to the development of psychoemotional stress, which manifests itself not only in behavioral and cognitive disorders, but also in the activation of hormonal systems and in an increase in pro-inflammatory immune reactions of the body. The relationship of neuroinflammation with the appearance of deviations in social behavior during isolation and the sexual characteristics of these processes remain poorly understood. In accordance with the theory of double hit, the effects of social isolation (SI), starting from adolescence, and activation of the immune system in early ontogenesis on the social behavior of male and female Wistar rats, as well as cytokine gene expression in various brain structures, were analyzed. On postnatal days 3 and 5 rats were injected with bacterial lipopolysaccharide (LPS) at a dose of 50 μg/kg or with saline solution (SAL). In the social preference test, rats of the SI group compared to rats in standard conditions (STAND) had higher preference coefficients. In the social dominance tube test, all SI group rats were more frequent winners in matches with rats from the STAND group. In the resident-intruder test, rats of the SI group in comparison to the STAND group had higher number of attacks, offensive uprights, holds, aggressive grooming, lateral threats. The greatest effect of SI in the resident-intruder test was on all males and females of the LPS group only; females of the SAL group didn't change their behavior. In males, but not in females, the expression of pro-inflammatory cytokine genes Tnf, Il-1beta, Il-6 and the anti-inflammatory cytokine gene Tgf-beta was increased regionally specific after SI in the amygdala, prefrontal cortex and hippocampus. In STAND group, the expression of gene Tgf-beta was higher in females than in males. Thus, SI led to an increase in the rats' social preference, dominant properties, and aggressiveness, which was accompanied by the triggering of pro-inflammatory reactions in the brain in males. The early proinflammatory stress made the LPS group females more vulnerable to the influence of SI.