SITE SPECIFIC REGULATION OF IMMUNE FUNCTION IN THE CNS

中枢神经系统免疫功能的位点特异性调节

• 批准号: 2591689
• 负责人: LYNNETTE Marie MCCLUSKEY
• 金额: $ 2.52万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-11-01 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/2591689
• 关键词: central nervous system; disease /disorder model; experimental allergic encephalomyelitis; interferon gamma; laboratory rat; multiple sclerosis; neuroanatomy; neuroimmunomodulation; neurotransmitters

The proposed experiments are based on the hypothesis that distinct neuroanatomical regions of the CNS of the rat will regulate immune cells differently in vivo, depending on the local profile of neurochemicals. Specifically, two major aspects of the cell-mediated immune response which are enhanced following interferon-gamma) injection - T cell traffic and MHC expression - are proposed to be differentially regulated by local CNS environments. Here, these aspects of immune function following INFO-gamma injection in the following regions: (1) the nucleus of the solitary tract (NTS), a brainstem region with primarily inhibitory neurochemicals, (2) the hippocampus, an area containing mainly excitatory neurotransmitters, and (3) the hypothalamus, a region with an abundance of neurohormones. The regulatory environments of the hippocampus and the hypothalamus are proposed to suppress T cell traffic and/or MHC expression, while enhancement of these parameters is expected to occur in the NTS. Pharmacological antagonists against specific neurochemicals will then be used to attribute differential regulation of immune function to major neurotransmitters. Finally, lesion formation after induction of experimental allergic encephalomyelitis, an animal model of multiple sclerosis, will be examined in these neuroanatomical regions to determine if pharmacological manipulation of neurotransmitters affects inflammation. The proposed studies will add insight into the factors that regulate the immune response to antigen in the CNS.

拟议的实验是基于这样一个假设，即不同于 大鼠中枢神经解剖区对免疫细胞的调节作用 在活体内不同，取决于神经化学物质的局部特征。 具体地说，细胞免疫反应的两个主要方面 在注射干扰素-伽马)-T细胞交通和MHC后增强 表达-被认为是由局部中枢神经系统差异调节的 环境。在这里，信息伽马后免疫功能的这些方面 注射于以下区域：(1)孤束核 (NTS)，主要含有抑制性神经化学物质的脑干区域，(2) 海马区，一个主要含有兴奋性神经递质的区域，以及 (3)下丘脑，这是一个神经激素丰富的区域。这个 海马体和下丘脑的调节环境是 建议抑制T细胞流量和/或MHC表达，而 这些参数的改进预计将在新界南进行。 针对特定神经化学物质的药理拮抗剂将被 用于将免疫功能的差异调节归因于 神经递质。最后，诱导后病变的形成 实验性变态反应性脑脊髓炎 硬化症，将在这些神经解剖区域进行检查，以确定 神经递质的药理操作是否会影响炎症。 拟议的研究将增加对调节 中枢神经系统对抗原的免疫反应。