|Budget Amount *help
¥2,100,000 (Direct Cost : ¥2,100,000)
Fiscal Year 1994 : ¥400,000 (Direct Cost : ¥400,000)
Fiscal Year 1993 : ¥1,700,000 (Direct Cost : ¥1,700,000)
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).
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