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Does the distribution of free D-serine, which is a potent activator of the NMDA receptor complex, coincide with the localization of D-amino acid oxidase in brains?

游离 D-丝氨酸（NMDA 受体复合物的有效激活剂）的分布是否与 D-氨基酸氧化酶在大脑中的定位一致？

基本信息

批准号：
06670166
负责人：
HORIIKE Kihachiro
金额：
$ 1.34万
依托单位：
Shiga University of Medical Science
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1994
资助国家：
日本
起止时间：
1994 至 1995
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-06670166/
关键词：
D-Amino Acid D-Serine D-Amino Acid Oxidase Central Nervous System Glia Astrocyte NMDA Receptor

项目摘要

D-Serine is a potent activator of the NMDA receptor complex. In various brain regions of the lower vertebrate species, D-serine levels were low. On the contrary, in the mammals, the contents of free D-serine were high in the forebrain (ca.400 nmol/g wet weight, the D/L ratio =0.4) , and low in the hindbrain. Free D-serine was shown not to be of microbial origin using germ-free mice.D-Serine binding in rat brain was high in the forebrain, especially the hippocampus, indicating that the distribution of NMDA receptor is high in the forebrain.D-Amino acid oxidase was absent or scarce in the forebrain, and was confined to the brain stem, spinal cord, and cerebellum. The oxidase-containing cells were exclusively astrocytes including Bergmann glial cells, and neither neuronal components, endothelial cells, oligodendrocytes nor ependymal cells showed the oxidase activity. The greater proportion of the oxidase activity was preset in the glial spaces around various kinds of synapses, and the activity was not associated with a specific kind of neuron, synapse or transmitter.The astrocytes regionally differentiate into two distinct types, one of which expresses the oxidase in the midbrain, rhombencephalon and spinal cord, and the other which dose not in the forebrain. That is, the oxidase gene expression is regulated in a regionally all-or-none fashion in the astrocytes. In the mammalian brains, the distribution of the oxidase is inversely correlated with those of free D-serine and NMDA receptor. These results indicate that the oxidase decomposes free D-amino acids including D-serine in the brain, and that the magnitude of its activity (the specific activity) is important in determining the regional concentrations of D-amino acids in the steady state.

D-丝氨酸是NMDA受体复合体的有效激活剂。在低等脊椎动物物种的不同脑区，D-丝氨酸水平都很低。反之，哺乳动物前脑中游离D-丝氨酸含量较高(约400nmol/g湿重，D/L比值=0.4)，后脑中D-丝氨酸含量较低。D-丝氨酸在大鼠脑内的结合量在前脑，尤其是海马区较高，说明NMDA受体在前脑中的分布较高；D-氨基酸氧化酶在前脑中缺失或稀少，仅局限于脑干、脊髓和小脑。含氧化酶的细胞仅为星形胶质细胞，包括Bergmann胶质细胞，神经元成分、内皮细胞、少突胶质细胞和室管膜细胞均不显示氧化酶活性。星形胶质细胞在区域上分化为两种不同的类型，一种在中脑、斜脑和脊髓表达，另一种在前脑不表达。也就是说，在星形胶质细胞中，氧化酶基因的表达是以一种要么全有要么全不的方式调节的。在哺乳动物的大脑中，氧化酶的分布与游离D-丝氨酸和NMDA受体的分布呈负相关。这些结果表明，该酶在大脑中分解包括D-丝氨酸在内的游离D-氨基酸，其活性(比活性)的大小对于确定D-氨基酸在稳态下的区域浓度是重要的。