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

中枢神经系统/免疫系统相互作用——遗传学/与行为疾病的相关性

• 批准号: 6290546
• 负责人: ESTHER M. STERNBERG
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF MENTAL HEALTH
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6290546
• 关键词: T lymphocyte; cell transplantation; clinical research; corticosterone; cytokine; embryo /fetus tissue transplantation; genetic polymorphism; human subject; hypothalamic pituitary axis; hypothalamus; inbreeding; inflammation; laboratory rat; linkage mapping; multiple sclerosis; nervous system transplantation; psychoneuroimmunology; stress

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

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。在近交系大鼠品系中的遗传连锁和分离研究，侧重于使用遗传连锁和分离鉴定近交系大鼠品系中炎性疾病易感性、HPA轴失调和应激行为反应模式的共遗传性状的遗传基础。目前的研究结果显示了我们正在研究的行为和炎症表型之间的几种联系。具体而言，使用F2在炎症易感和耐药大鼠品系中的互交，我们已经确定了两个连锁区域，一个在染色体10上，一个在染色体2上，与角叉菜胶诱导的液体渗出的性状相关联，角叉菜胶诱导的液体渗出是更复杂的自身免疫性炎症疾病的亚表型。10号染色体连锁区与人类17号染色体上的一个区域同线，该区域与多种自身免疫性炎性疾病相关。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。目前的研究集中在评估这些连锁区域内的候选基因的突变，确定突变的功能意义，并进一步精细定位这些区域。行为研究的重点是进一步精细映射的连锁区域。临床研究也在进行中，以确定候选基因中的相关突变是否存在于人类自身免疫性疾病受试者中。- HPA轴; CRH;应激;神经免疫相互作用;炎症性疾病;动物模型;大鼠;遗传连锁和分离-人类受试者