CYTOKINE CORRELATES OF SEX SPECIFIC AGGRESSIVE BEHAVIOR FOLLOWING EARLY LIFE SOCIAL ISOLATION

Brain, a relatively immune-privileged organ, undergoes an aberrant influx of immune cells and cytokines during pathological conditions. Apart from astrocytes and microglia, immune cells entering the brain from circulation also cause inflammation. The cytokines produced by these immune cells not only cause neuroinflammation but are also observed to affect the behavior of an individual. Early life stressful experiences drive lasting behavioral deficits though peripheral as well as central immune correlates including cytokines are still obscure. Here, we have investigated brain region specific cytokine state in mouse model of post weaning social isolation (PWSI) induced behavioral deficits. We found that male Balb/c mice exposed to PWSI exhibited a marked increase in aggression, whereas female mice displayed resilience and did not show aggressive behavior. Cytokine profiling revealed that transcript levels of interleukin-6 (IL-6) and responsive genes were significantly downregulated in the hypothalamus of both sexes subjected to PWSI, though there was differences in magnitude. Of note, other pro-inflammatory cytokines including IFN-gamma (IFN-γ), and IL-1beta (IL-1β) were unaffected in both sexes. These findings suggest that hypothalamic IL-6 signaling might be associated with sex-specific regulation of aggressive behavior following early-life social stress. These findings will eventually help us find potential immune biomarkers related to trauma induced aggression in humans, which might be useful for reducing the aggression phenotype.