Regulation of Glycine Neurotransmission by the Glial Glycine Transporter 1.

神经胶质细胞甘氨酸转运蛋白对甘氨酸神经传递的调节 1。

• 批准号: 5430338
• 负责人: Professor Dr. Volker Eulenburg
• 金额: --
• 依托单位: Abteilung für Neurobiologie
• 依托单位国家: 德国
• 项目类别: Priority Programmes
• 财政年份: 2004
• 资助国家: 德国
• 起止时间: 2003-12-31 至 2010-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/5430338?language=en
• 关键词: Regulation; Glycine; Neurotransmission; Glial; Transporter

Neurotransmitter transporters are crucial for the rapid termination of synaptic transmission and constitute important targets of different widely prescribed drugs. The glial glycine transporter 1 (GlyT1) is thought to have important roles in the regulation of both inhibitory glycinergic and excitatory N-methyl-D-aspartate (NMDA) receptor-mediated neurotransmission. In addition, it constitutes an important target in medication development for schizophrenia. Knockout of the GlyT1 gene causes early postnatal lethality in mice due to over-inhibition of respiratory rhythmogenesis. Here, we propose to study the functions of GlyT1 in the adult CNS by using mouse lines which either contain only a single active GlyT1 allele or express increased levels of the transporter in glial cells, due to Cre/lox driven activation of a silent GlyT1 transgene. Biochemical, immunocytochemical, electrophysiological and behavioural analyses of such mice will be used to disclose the specific roles of GlyT1 at inhibitory and excitatory synapses. In addition, the work proposed may help to generate animal models of schizophrenia.

神经递质转运蛋白对于突触传递的快速终止至关重要，并且是不同广泛处方药物的重要靶点。胶质甘氨酸转运蛋白 1 (GlyT1) 被认为在调节抑制性甘氨酸能和兴奋性 N-甲基-D-天冬氨酸 (NMDA) 受体介导的神经传递中发挥重要作用。此外，它也是精神分裂症药物开发的一个重要目标。 GlyT1 基因的敲除会因呼吸节律发生的过度抑制而导致小鼠产后早期死亡。在这里，我们建议通过使用仅含有单个活性 GlyT1 等位基因或由于 Cre/lox 驱动沉默 GlyT1 转基因激活而在神经胶质细胞中表达增加水平的转运蛋白的小鼠品系来研究 GlyT1 在成人 CNS 中的功能。对此类小鼠的生化、免疫细胞化学、电生理学和行为分析将用于揭示 GlyT1 在抑制性和兴奋性突触中的具体作用。此外，所提出的工作可能有助于产生精神分裂症的动物模型。