Evaluation of the mechanism of membrane transport of metal ions in the central nervous system

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神经传递的关系。目前的调查结果如下：1。测定LEC大鼠脑内微量元素和神经递质（去甲肾上腺素（NE）、多巴胺（DA））及其代谢物浓度；威尔逊病的动物模型LEC大鼠的NE抑制和DA在大脑皮层的积累发生在年轻时。幼龄时儿茶酚胺代谢的改变可能是由于该区域铜缺乏导致DBH活性降低。我们的研究结果提出了一种假设，即威尔逊病早期脑铜缺乏引起的神经化学变化可能参与了该疾病患者在脑铜过量积聚之前的神经功能障碍。在LEA大鼠的各个器官中，测定了导致Wilson病的铜转运蛋白ATP7B的分布。在CA1 ~ CA4锥体细胞、脑齿状回颗粒细胞和肾皮质等多个神经元细胞组中均检测到ATP7B。这些结果表明，ATP7B在Cu稳态调控和组织中全铜结合蛋白的生物合成中起重要作用。

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 neurotransmission. Results obtained in the present investigations are as follows ;1.We determined concentrations of trace elements and neurotransmitters (norepinephrine (NE) , dopamine (DA) ) and its metabolites in the brain of LEC rat ; an animal model of Wilson disease. NE depression as well as accumulation of DA in the cerebral cotex of the LEC rat occurred at a young age. These alterrations of the catecholamine metabolism at a young age may be due to the depression of DBH activity induced by Cu deficiency in this region. Our results suggest the hypothesis that neurochemical changes induced by brain Cu deficiency in the early stage of Wilson disease may be involved in the neurological disturbances in patients with this disease before excessive Cu accumulation in the brain.2.Distribution of ATP7B,the copper-transporting protein responsible for Wilson disease, was determined in various organs of the LEA rat. ATP7B was detected in several neuronal cell groups such as pyramidal cells of CA1 to CA4 and granular cells of the dentate gyrus in the brain and the renal cortex of the kidney. These results suggest that ATP7B plays an important role in the regulation of Cu homeostasis and biosynthesis of holo-Cu-binding proteins in tissues.