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

神经内分泌免疫学和行为学部分的研究重点是动物和人类中枢神经系统-免疫系统相互作用的几个方面。这些研究旨在确定神经免疫相互作用的病理生理学相关性和潜在机制，特别关注下丘脑-垂体-肾上腺（HPA）轴-免疫系统相互作用。项目1。自交系大鼠的遗传连锁和分离研究，主要利用遗传连锁和分离技术，确定自交系大鼠炎症易感性、HPA轴失调和应激行为反应模式等共遗传性状的遗传基础。目前的研究结果表明，我们正在研究的行为和炎症表型之间存在一些联系。具体来说，通过对炎症易感和耐药大鼠品系的F2交叉，我们已经确定了两个连锁区域，一个在第10染色体上，一个在第2染色体上，与卡拉胶诱导的液体分泌的性状有关，这是一种更复杂的自身免疫性炎症疾病的亚表型。10号染色体连锁区域与人类17号染色体上与多种自身免疫性炎症疾病相关的区域是同源的。该区域还包含几个在HPA轴反应中起作用的候选基因，包括CRH受体。目前的研究主要集中在评估这些突变连锁区域内的候选基因，确定所鉴定的突变的功能意义，并进一步对这些区域进行精细定位。行为学研究的重点是进一步精细映射连锁区域。临床研究也在进行中，以确定候选基因的相关突变是否存在于人类自身免疫性疾病的受试者中。- HPA轴；CRH;压力;neural-immune交互;炎症性疾病;动物模型;大鼠;遗传连锁和分离-人类受试者

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. - HPA axis; CRH; stress; neural-immune interactions; inflammatory disease; animal models; rats; genetic linkage and segregation - Human Subjects