Cell Biological Compartmentation of Brain Histamine

脑组胺的细胞生物区室

基本信息

批准号：
05670090
负责人：
YAMATODANI Atsushi
金额：
$ 1.34万
依托单位：
Osaka University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1993
资助国家：
日本
起止时间：
1993 至 1994
项目状态：
已结题

项目摘要

The existence of several kinds of histamine-producing cells in the brain, such as neuronal dells, mast cells, vascular endothelial cells and microglias, has made it rather difficult to elucidate possible physiological roles of histamine in the central nervous system. To investigate pathophysiological significance of brain histamine, it is also very important to analyze the dynamics of histamine in the respective cellular pools. In this respect, I conducted following experiments, especially focused on the cellular basis of cytokine-induced histidine decarboxylase activity.Primary culture of brain tissues was performed using fetal rat hypothalamus and cerebral cortex. After several days of culture, the cells were further incubated with lipopolysaccharide for several hours. The histidine decarboxylase activities in the hypothalamic cell culture increased dose dependently, however, those in the cortical culture did not change. Similar results were obtained by using interleukin 1beta(IL1). … More These results indicate that the induction of histamine forming activity by cytokine have occurred in the histaminergic neuros, but not in the microglia or other cells. Because histaminergic neuros are exclusively confined to the hypothalamic tuberomammillary nucleus. To confirm this result, I examined the in vivo histamine release form the anterior hypothalamic area after microinjection of IL1 into the tuberomammillary nucleus using a microdialysis technique. The injection of IL1 caused increase of histamine release in a dose-dependent manner. In the peripheral tissues, we have already demonstrated that IL1 induces histidine decarboxylase expression in macrophages, which are equivalent to microglias in the brain. However, present results suggest that cells responsible to the induction of histamine forming and releasing activities are histaminergic neurons. Thus, brain histamine may serve as a transmitter for the cross talk between the immune system and the nervous system in the central nervous system. It is also interesting that histamine may contribute to the pathophysiology of Alzheimer disease. Less

大脑中存在多种产生组胺的细胞，例如神经元细胞、肥大细胞、血管内皮细胞和小胶质细胞，使得阐明组胺在中枢神经系统中可能的生理作用和研究病理生理学意义变得相当困难。脑组胺的研究，分析各个细胞池中组胺的动态也非常重要。在这方面，我进行了以下实验，特别关注细胞因子诱导的组氨酸的细胞基础。脱羧酶活性。使用胎鼠下丘脑和大脑皮层进行脑组织的原代培养，培养数天后，将细胞进一步与脂多糖一起培养数小时，但下丘脑细胞培养物中的组氨酸脱羧酶活性呈剂量依赖性增加。使用白细胞介素 1β(IL1) 获得了类似的结果。这些结果表明诱导组胺形成活性。细胞因子的作用发生在组胺能神经元中，但不在小胶质细胞或其他细胞中，因为组胺能神经元仅局限于下丘脑结节乳头核，为了证实这一结果，我检查了显微注射后下丘脑前部区域的组胺释放。使用微透析技术将 IL1 注射到结节乳头核中，导致外周组织中组胺的释放量呈剂量依赖性增加。已经证明 IL1 会诱导巨噬细胞中的组氨酸脱羧酶表达，而巨噬细胞相当于大脑中的小胶质细胞。然而，目前的结果表明，负责诱导组胺形成和释放活动的细胞是组胺能神经元，因此，大脑中的组胺可能是一种递质。对于中枢神经系统中免疫系统和神经系统之间的相互作用，组胺可能有助于阿尔茨海默病的病理生理学。