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: 6111158
• 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/6111158
• 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 suggest several linkages with both the behavioral and inflammation phenotypes we are examining. In these studies additional animals must be genotyped in order to confirm the significance of these possible linkage sites. Project 2., "Whole-blood cytokine production and glucocorticoid sensitivity in humans" focuses on defining in human subjects the relationship of variations in HPA axis responsiveness to variations in immune system responsiveness and symptoms of affective disorder. This study utilizes a whole blood cytokine production and glucocorticoid sensitivity assay which we have found to be sensitive to physiological variations in ambient glucocorticoid levels. Most recently we have found differences in glucocorticoid sensitivity in different clinical sub-populations of multiple sclerosis patients. Project 3., "Hypothalamic intracerebroventricular transplantation of neuronal tissue: effects on experimental models of autoimmune/inflammatory disease". This project focuses on defining the pathophysiologic consequences of reconstitution of the HPA axis by intracerebroventricular transplantation of fetal neuronal tissue in autoimmune/inflammatory diseases in inbred rat strains. Results indicate that fetal neuronal tissue transplantation differentially affects expression of different models of experimentally-induced inflammatory/autoimmune diseases, with the major specific effect on suppression of innate (non-thymic dependent) models of inflammation. This suppression in part appears to act through the HPA axis.

神经内分泌科的研究 免疫学和行为学集中在几个方面的中心 动物神经系统-免疫系统相互作用， 人类这些研究的目的是确定病理生理 神经免疫相互作用的相关性和潜在机制， 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，“遗传联系和 近交系大鼠品系的分离研究”，重点是确定 炎症性疾病共同遗传特征的遗传基础 易感性、HPA轴失调和行为模式 应激反应的近交系大鼠品系，使用遗传连锁和 种族隔离目前的研究结果表明， 行为和炎症表型。在这些 研究必须对额外的动物进行基因分型才能确认 这些可能的连接点的重要性。项目二， “全血细胞因子的产生和糖皮质激素的敏感性， 人类”的重点是定义人类主体的关系， HPA轴对免疫反应的变化 系统反应性和情感障碍的症状。这 研究利用全血细胞因子产生和糖皮质激素 敏感性试验，我们发现对 环境糖皮质激素水平的生理变化。最 最近，我们发现， 多发性硬化症患者的不同临床亚群。 项目3，“下丘脑脑室内移植 神经元组织：对实验模型的影响 自身免疫性/炎症性疾病”。该项目的重点是 定义重建的病理生理后果， 胎鼠侧脑室移植对HPA轴的影响 近交系大鼠自身免疫性/炎症性疾病中的神经元组织 菌株结果表明，胎儿神经元组织移植 差异影响不同模型的表达 实验诱导的炎性/自身免疫性疾病， 抑制先天性（非胸腺） 依赖性）炎症模型。这种抑制在某种程度上 似乎通过HPA轴起作用。