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）：本研究建议的长期目标是了解D丝氨酸在兔视网膜中的功能，以及它如何通过其作为NMDA受体的内源性辅助剂的作用来调节神经节和无藻细胞的兴奋性。 D-丝氨酸由Muller细胞和星形胶质细胞合成并释放，并代表一种新形式的神经神经神经元调节。电生理方法将用于评估应用D丝氨酸的直接作用，并通过生化/药理学方法来实现内源性D-丝氨酸的减少。重要的是要了解DSERINE在视网膜中的重要性，因为NMDA受体已经与许多神经组织的功能有关，包括通过谷氨酸过度刺激从缺血性或患病组织释放的谷氨酸刺激介导的兴奋性效应。此外，目前大量为精神病患者提供了D-丝氨酸。由于D丝氨酸可以越过血脑屏障，因此无疑可以进入视网膜。因此，如果D-塞林成为患者批准的治疗，则D丝氨酸代表了视网膜的潜在健康风险，并且对视网膜的行为和监管的了解至关重要。