D-serine modulates retinal neurocircuitry operations

D-丝氨酸调节视网膜神经回路操作

• 批准号: 7153492
• 负责人: Brian G Reed
• 金额: $ 4.98万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-12-01 至 2007-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7153492
• 关键词: AMPA Receptors; Affinity; Amacrine Cells; Amino Acids; Astrocytes; Biochemical; Blood - brain barrier anatomy; Capillary Electrophoresis; D-Amino Acid Dehydrogenase; Ganglia; Generations; Glutamates; Health; Knowledge; Light; Measurement; Mediating; Methods; Muller' s cell; Myxoid cyst; N-Methyl-D-Aspartate Receptors; NMDA receptor antagonist; Nerve Tissue; Neurons; Operative Surgical Procedures; Oryctolagus cuniculus; Patients; Phenazines; Physiological; Play; Purpose; Receptor Activation; Reducing Agents; Regulation; Research Proposals; Retina; Retinal; Retinal Ganglion Cells; Risk; Role; Serine; Site; Testing; Therapeutic; Tissues; Whole-Cell Recordings; extracellular; ganglion cell; postsynaptic; receptor; response; retinal neuron

DESCRIPTION (provided by applicant): The long-term objectives of this research proposal are to understand the function of D-serine in the rabbit retina and how it modulates the excitability of ganglion and amacrine cells through its actions as the endogenous coagonist of NMDA receptors. D-serine is synthesized and released by Muller cells and astrocytes and represents a new form of glial-neuronal modulation. Electrophysiological methods will be used to evaluate the direct actions of applied D-serine and reductions of endogenous D-serine will be achieved through biochemical/pharmacological methods. It is essential to understand the importance of Dserine in the retina, because NMDA receptors have been implicated in many functions of nervous tissue, including excitoxicity effects mediated through excessive stimulation by glutamate released from ischemic or diseased tissue. In addition, D-serine is presently given in large quantities for therapeutic purposes to psychiatric patients. Because D-serine can cross the blood brain barrier, it undoubtedly can enter the retina. Thus D-serine represents a potential health risk to the retina and knowledge of its actions and regulation in the retina are essential if D-serine becomes approved therapy for patients.

描述（由申请人提供）：本研究计划的长期目标是了解 D-丝氨酸在兔视网膜中的功能，以及它如何通过其作为 NMDA 受体内源性共激动剂的作用来调节神经节细胞和无长突细胞的兴奋性。 D-丝氨酸由米勒细胞和星形胶质细胞合成和释放，代表了一种新形式的胶质神经元调节。将使用电生理学方法来评估应用的 D-丝氨酸的直接作用，并通过生化/药理学方法实现内源性 D-丝氨酸的减少。了解丝氨酸在视网膜中的重要性至关重要，因为 NMDA 受体与神经组织的许多功能有关，包括通过缺血或患病组织释放的谷氨酸的过度刺激介导的兴奋毒性效应。此外，目前为了治疗精神病患者的目的而大量给予D-丝氨酸。由于D-丝氨酸可以穿过血脑屏障，因此毫无疑问可以进入视网膜。因此，D-丝氨酸对视网膜具有潜在的健康风险，如果 D-丝氨酸被批准用于患者治疗，那么了解其在视网膜中的作用和调节是至关重要的。