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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

脑内存在多种组胺产生细胞，如神经元细胞、肥大细胞、血管内皮细胞和小胶质细胞，这使得阐明组胺在中枢神经系统中可能的生理作用变得相当困难。为了研究脑组织组胺的病理生理意义，分析组胺在相应细胞池中的动力学也是非常重要的。在这方面，我进行了以下实验，特别是专注于精氨酸诱导的组氨酸脱羧酶活性的细胞基础。培养数天后，将细胞与脂多糖进一步孵育数小时。组氨酸脱羧酶活性在下丘脑细胞培养中呈剂量依赖性增加，但在皮质培养中没有变化。使用白细胞介素1 β（IL 1）获得了类似的结果。 ...更多信息这些结果表明，细胞因子诱导组胺形成活性发生在组胺能神经元，而不是在小胶质细胞或其他细胞。因为组胺能神经只局限于下丘脑结节乳头核。为了证实这一结果，我研究了在体内组胺释放的前下丘脑区后，微量注射IL-1到结节乳头核使用微透析技术。注射IL-1后，组胺释放量呈剂量依赖性增加。在外周组织中，我们已经证明IL 1诱导巨噬细胞中组氨酸脱羧酶的表达，巨噬细胞相当于脑中的小胶质细胞。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，脑组胺可能充当中枢神经系统中免疫系统和神经系统之间串扰的传递者。同样有趣的是，组胺可能有助于阿尔茨海默病的病理生理学。少