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Functional correlations between hypothalamus and splenic sympathetic nervous system under environmental stress and immune response

环境应激与免疫反应下下丘脑和脾交感神经系统的功能相关性

基本信息

批准号：
10470015
负责人：
SHIMIZU Nobuaki
金额：
$ 3.84万
依托单位：
kanazaw University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B).
财政年份：
1998
资助国家：
日本
起止时间：
1998 至 2000
项目状态：
已结题

项目摘要

Various kinds of stressful stimuli stimulate central sympathetic outflow to peripheral nerve endings, and the autonomic nervous system is thought to serve as a major communication link between the brain and the immune system. The purpose of this research project was to study the possible mechanisms of the hypothalamic function in modulating the peripheral immune system, and verify the direct linkage between the activity of the splenic sympathetic nerve and the cytotoxicity of NK cells in the spleen. To further clarify the functional roles of transmitter substances on the behavioral abnormalities caused by the emotional stress, the effects of immobilization stress on food intake were also investigated.1) Significant reduction of daily food intake was observed after 2 hr immobilization and injection of methysergide antagonized the immobilization-induced anorexia for 3 hr. Brain microdialysis clarified the immobilization induced serotonin release in the hypothalamus. Injection of 8-OH-DPA … More T itself had no effect on basal release of serotonin, while it significantly blocked the immobilization induced serotonin release in the lateral hypothalamus and stress induced anorexia These results suggest that immobilization-induced anorexia is mediated at least in part through serotonergic mechanisms in the hypothalamus.2) In vivo microdialysis technique was adopted for chronic monitoring of splenic noradrenaline (NA) release in rats. Immobilization stress caused a rapid increase in the NA release release to about 800% of basal release in conjunction with suppression of NK cell activity in the spleen. Surgical denervation of the splenic sympathetic nerve significantly attenuated the elevated level of NA and also inhibited the immobilization-induced suppressive effect on NK activity. Intracerebroventricular injection of corticotropin releasing factor (2 μg/rat) or intraperitoneal injection of interleukin 1-β ( 50 ng/kg), which suppress the NK activity, significantly increased the splenic NA release. These results suggest that NA has an important role in the control of neuroimmunomodulation in the spleen. Less

各种应激刺激刺激中枢交感神经流出至周围神经末梢，自主神经系统被认为是大脑和免疫系统之间的主要沟通纽带。本研究的目的是研究下丘脑功能调节外周免疫系统的可能机制，并验证脾交感神经活性与脾NK细胞杀伤活性之间的直接联系。为了进一步阐明递质在情绪应激引起的行为异常中的作用，我们还研究了束缚应激对大鼠摄食量的影响。1)束缚2小时后，大鼠的每日摄食量显著减少，注射甲基丝氨酸甲酯3小时可拮抗束缚所致的厌食症。脑微透析澄清了固定诱导的下丘脑5-羟色胺释放。注射用8-羟基二苯基丙交酯…More T本身对5-羟色胺的基础释放无影响，但可显著阻断束缚诱导的下丘脑5-羟色胺释放和应激性厌食。这些结果提示，束缚诱导的厌食症至少部分是通过下丘脑5-羟色胺能机制介导的。2)在体微透析技术用于慢性监测大鼠脾去甲肾上腺素(NA)的释放。束缚应激导致NA释放迅速增加，达到基础释放的800%左右，同时抑制了脾中NK细胞的活性。外科手术切断脾交感神经可显着减轻NA升高的水平，也可抑制制动对NK活性的抑制作用。侧脑室注射促肾上腺皮质激素释放因子(2μg/只)或腹腔注射白细胞介素1-β(50 ng/kg)抑制NK活性，可显著增加脾NA的释放。这些结果提示，NA在控制脾的神经免疫调节中起着重要作用。较少