Research Project
10266793
PROJECT SUMMARY Social networks and support are integral to health and wellness across the lifespan, and social engagement may be particularly important to preserve overall health and cognitive function during aging. However, social behavior and social cognition decline during aging. A better understanding of the neural mechanisms underlying healthy and abnormal social behaviors is fundamental to increasing healthy aging outcomes. Social behaviors are supported by the ?reward? circuitry, a network of brain regions that develops during adolescence. We have shown that microglia, the resident immune cells of the brain, play a crucial role in reward circuitry and social behavior development in adolescent rats. Microglia phagocytose and eliminate, or ?prune?, synaptic receptors in the nucleus accumbens (NAc) reward region between pre-early adolescence in females, and between early-mid adolescence in males. Interfering with microglia-mediated NAc pruning during each sex- specific pruning stage altered social behavior development in both sexes. In this proposal, we will determine how healthy and abnormal immune signaling in the NAc during adolescence sex-specifically shapes social behavior across the lifespan. Specifically, we will determine whether (1) interfering with NAc pruning in adolescent male and female rats increases social behaviors across the lifespan, (2) social stress during adolescence, a pro-inflammatory stimulus that impairs reward circuitry and social behavior development, exacerbates microglial pruning in the NAc, and (3) social stress during adolescence worsens aging-related social behavior dysfunction. Our core hypothesis is that healthy microglia- mediated pruning in the NAc during adolescence supports social behavior throughout the lifespan, and that the sex-specific developmental stages during which NAc pruning occurs will thus constitute sex-specific periods of vulnerability for life long social abnormalities. These studies treat developmental stage and sex as independent variables to advance our understanding of how healthy and abnormal adolescent development in the NAc impacts social behavior and neuro-immune signaling across the lifespan. The successful completion of this proposal will produce novel insights regarding the impact of aberrant sex-specific developmental mechanisms during adolescence that may be important for healthy aging outcomes.
