Elucidation of the mechanism of membrane transport of metal ions in the central nervous system and the relation to brain function

本研究旨在探讨金属离子在中枢神经系统中的膜转运机制及其与脑功能的关系。目前的调查结果如下：1。利用免疫组织化学技术，观察了大鼠脑、肾、小肠和肝脏中铜转运p型atp酶（ATP7B）的定位，ATP7B是威尔逊病的基因产物。ATP7B在大鼠大脑海马区神经元细胞、嗅球、小脑、脑干皮层和脑核、肾脏外髓质皮层和外条纹、小肠Paneth细胞和肝细胞中均检测到。ATP7B主要存在于大量铜和铜结合蛋白（如Cu-ZnSOD、金属硫蛋白和NO合成酶）存在的区域。因此，在正常组织中，ATP7B被认为不仅调节铜稳态和全铜结合蛋白的生物合成，而且还调节cns中的NO合成。研究了衰老加速小鼠P10（SAMP10）脑内微量元素和神经递质浓度随年龄变化的变化，SAMP10表现为脑萎缩和学习记忆功能减退。SAM-P10大部分区域的Zn、Cu和Mn浓度显著低于对照组。SAM-P10脑内Mo浓度显著高于对照组。与对照组相比，观察到12月龄海马SAM-P10 CA3区谷氨酸和甘氨酸释放量过量。这些结果表明，中枢神经系统金属离子的异常膜转运可导致SAMP10脑加速衰老。

In the present study, we intended to evaluate the mechanism of membrane transport of metal ions in the central nervous system and its relation to the brain function. Results obtained in the present investigations are as follows;1. Localization of copper-transporting P-type ATPase (ATP7B), a gene product responsible for Wilson disease, was visualized in the brain, kidney, small intestine and liver of the Long-Evans agouti rat using immunohistochemical technique. The ATP7B was intensely detected in neuronal cells of the hippocampal formation, olfactory bulbs, cerebellum, cerebral cortex and nuclei in the brain stem of the rat brain, the cortex and the outer stripe of the outer medulla in the kidney, Paneth cells of the small intestine, and hepatocytes. ATP7B was observed predominantly in the regions in which high amounts of copper and copper-binding proteins such as Cu-ZnSOD and metallothionein and NO synthase were detected. Thus, in normal tissue, ATP7B was considered to regulate not only copper homeostasis and biosynthesis of holo copper-binding proteins but also NO synthesis in CNS.2.. Changes in concentrations of trace elements and neurotransmitters by aging were determined in the brain of Senescence-Accelerated Mouse P10(SAMP10), which showed brain atrophy and deficits in learning and memory. Zn, Cu and Mn concentrations in most regions of SAM-P10, were significantly lower than those in the control rat. Mo concentration in the brain of SAM-P10 was significantly higher than that in the control. The excess amount of glutamate and glycine release from the hippocampal CA3 regions of SAM-P10 aged 12 months was observed as compared to that in the control. These results suggest that abnormal membrane transports of metal ions in CNS induce senescence-acceleration of the brain of SAMP10.