CNS/IMMUNE SYSTEM INTERACTION--GENETICS/RELEVANCE TO BEHAVIORAL ILLNESS

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The research of the Section on Neuroendocrine Immunology and Behavior focuses on several aspects of central nervous system - immune system interactions in animals and humans. These studies aim at defining the pathophysiological relevance and underlying mechanisms of neuroimmune interactions, with particular focus on hypothalamic-pituitary-adrenal (HPA) axis - immune system interactions. Project 1. "Genetic linkage and segregation studies in inbred rat strains", focuses on identifying the genetic basis for co-inherited traits of inflammatory disease susceptibility, HPA axis dysregulation and patterns of behavioral responses to stress in inbred rat strains, using genetic linkage and segregation. Current findings show several linkages with both the behavioral and inflammation phenotypes we are examining. Specifically, using an F2 intercross in inflammatory susceptible and resistant rat strains, we have identified two linkage regions, one on chromosome 10 and one on chromosome 2, linking with the trait of carrageenan induced fluid exudation, a sub-phenotype of more complex autoimmune inflammatory disease. The chromosome 10 linkage region is syntenic with a region on human chromosome 17 that links to a variety of autoimmune inflammatory diseases. This region also contains several candidate genes that play a role in HPA axis responses, including the CRH receptor. Current studies are focused on evaluating candidate genes within these linkage regions for mutations, determining the functional significance of mutations identified, and further fine mapping of these regions. Behavioral studies are focused on further fine mapping of linkage regions. Clinical studies are also underway to determine whether related mutations in candidate genes are present in subjects with human autoimmune disease.