Serine racemase is predominantly localized in neurons in mouse brain
Serine racemase is predominantly localized in neurons in mouse brain
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DOI：
10.1002/cne.21822
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发表时间：
2008-10-20
影响因子：
2.5
通讯作者：
Mori, Hisashi
中科院分区：
文献类型：
--
作者：
Miya, Kazushi;Inoue, Ran;Mori, Hisashi
D-丝氨酸是N-甲基-D-天冬氨酸（NMDA）型谷氨酸受体（GluR）通道甘氨酸结合位点的内源性配体，参与调节突触可塑性、神经网络形成和神经退行性疾病。丝氨酸消旋酶（serine racemase，SR）是由L-丝氨酸合成D-丝氨酸的一种酶。然而，最近在神经元中检测到SR mRNA及其蛋白。在这项研究中，我们研究了SR分布在出生后的发展过程中，并在培养的细胞中使用新的SR基因敲除小鼠作为阴性对照。我们发现SR主要定位于大脑皮层和海马CA 1区的锥体神经元。双重免疫荧光染色显示SR信号与神经元特异性核蛋白共定位，但不与星形胶质细胞标志物胶质细胞酸性蛋白和3-磷酸甘油酸脱氢酶共定位。在纹状体，我们观察到γ-氨基丁酸（GABA）能的中型棘神经元SR的表达。此外，在成人小脑，我们检测到弱，但显着的SR信号在GABA能浦肯野细胞。从这些发现中，我们得出结论，SR主要在大脑中的许多类型的神经元中表达，并在生理和病理条件下通过产生神经调节剂D-丝氨酸调节大脑功能中起着关键作用。
D-Serine is the endogenous ligand for the glycine binding site of the N-methyl-D-aspartate (NMDA)-type glutamate receptor (GluR) channel and is involved in the regulation of synaptic plasticity, neural network formation, and neurodegenerative disorders. D-Serine is synthesized from L-serine by serine racemase (SR), which was first reported to be localized in astrocytes. However, recently, SR mRNA and its protein have been detected in neurons. In this study, we examined the SR distribution in the brain during postnatal development and in cultured cells by using novel SR knockout mice as negative controls. We found that SR is predominantly localized in pyramidal neurons in the cerebral cortex and hippocampal CA1 region. Double immunofluorescence staining revealed that SR signals colocalized with those of the neuron-specific nuclear protein, but not with the astrocytic markers glial fibrillary acid protein and 3-phosphoglycerate dehydrogenase. In the striatum, we observed SR expression in gamma-aminobutyric acid (GABA)ergic medium-spiny neurons. Furthermore, in the adult cerebellum, we detected weak but significant SR signals in GABAergic Purkinje cells. From these findings, we conclude that SR is expressed predominantly in many types of neuron in the brain and plays a key role in the regulation of brain functions under physiological and pathological conditions via the production of the neuromodulator D-serine.