Role of neuroendocrine stress response in inflammatory a

神经内分泌免疫学和行为学部分的研究集中在动物和人类中枢神经系统-免疫系统相互作用的几个方面。这些研究旨在确定下丘脑-垂体-肾上腺(HPA)轴-免疫系统相互作用的潜在机制，这些相互作用与自身免疫性炎症性疾病的易感性和抵抗力以及应激行为反应的病理生理学相关性。项目1。《近交系大鼠品系的遗传连锁和分离研究》，利用遗传连锁和分离，重点确定近交系大鼠品系中炎症性疾病易感性、HPA轴失调和应激行为反应模式等共遗传特征的遗传基础。这些遗传连锁和分离研究已经完成，并表明在炎性敏感和耐药大鼠品系的F2杂交中，两个区域，一个在10号染色体上，一个在2号染色体上，与先天(卡拉胶诱导的)炎症有关，这是更复杂的自身免疫性炎症性疾病的一种亚型。10号染色体连锁区(与人类17号染色体上与多种自身免疫性炎症性疾病相连的区域同线)包含几个候选基因，包括CRH受体1和ACE，它们在HPA轴调节中发挥作用。CRH-R1的编码区没有突变，ACE的点突变在炎症特征中不起作用。这些研究的遗传连锁和分离阶段已经结束，目前的研究重点是通过使用表达微阵列来确定感兴趣的候选基因。这两种方法的结果将被合并，以识别感兴趣的基因，以便进一步研究。初步研究表明，有几个潜在的候选基因正在通过RT-PCR、原位杂交和适当组织的免疫组织化学进行验证。这些发现与感染性休克等疾病的易感性和抵抗力的危险因素直接相关。除了揭示感兴趣的潜在候选基因外，遗传连锁和分离研究表明，遗传因素只对QTL的变异有35%的贡献。因此，目前的研究还侧重于确定导致HPA轴的环境变异性和炎症特征的早期发育因素。这些研究表明，母亲的行为、性别和遗传因素相互作用，对这些菌株的HPA轴反应的成人设定点做出贡献。

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 underlying mechanisms of hypothalamic-pituitary-adrenal (HPA) axis - immune system interactions pathophysiological relevance of these interactions to susceptibility and resistance to autoimmune inflammatory diseases and behavioral responses to stress. Project 1. "Genetic linkage and segregation studies in inbred rat strains", focused 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. These genetic linkage and segregation studies have been completed and indicate in an F2 intercross of inflammatory susceptible and resistant rat strains, that two regions, one on chromosome 10 and one on chromosome 2, link with innate (carrageenan-induced) inflammation, a sub-phenotype of more complex autoimmune inflammatory disease. The chromosome 10 linkage region (syntenic with a region on human chromosome 17 that links to a variety of autoimmune inflammatory diseases) contains several candidate genes, including the CRH receptor type 1 and ACE, that play a role in HPA axis regulation. There is no mutation in the coding region of CRH-R1 and the point mutation in ACE does not play a role in the inflammatory trait. The genetic linkage and segregation phase of these studies has been terminated and current studies focus on identifying candidate genes of interest through the use of expression microarrays. Results from these two approaches will be merged to identify genes of interest for further study. Preliminary studies indicate several potential candidate genes of interest that are being validated by RT-PCR, in situ hybridization and immunohistochemistry of appropriate tissues. These findings have immediate relevance to risk factors for susceptibility and resistance to conditions including septic shock. In addition to shedding light on potential candidate genes of interest, the genetic linkage and segregation studies indicated that genetic factors contributed to only 35% of variance of the QTL. Current studies therefore also focus on identifying early developmental factors contributing to the environmental variability of the HPA axis and inflammatory traits. These studies indicate that maternal behavior, gender and genetic factors interact to contribute to the adult set-point of the HPA axis response in these strains.