AGE-INDUCED CHANGES IN MONOAMINE PRESYNAPTIC FUNCTION

年龄引起的单胺突触前功能的变化

• 批准号: 3070585
• 负责人: Greg A. Gerhardt
• 金额: $ 5.37万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 1989
• 资助国家: 美国
• 起止时间: 1989-04-01 至 1994-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3070585
• 关键词: GABA receptor; adrenergic receptor; afferent nerve; aging; cerebellum; corpus striatum; electrophysiology; evoked potentials; high performance liquid chromatography; laboratory rat; neurotransmitter metabolism; synapses

This RCDA proposal deals with the investigation of dynamic presynaptic changes in monamine-containing afferents that may occur during aging in brain areas known to regulate balance and gait (ie. striatum and cerebellum). With RCDA support, I hope to remain in a medical school academic environment and focus on age-related changes in the monoaminergic systems of the CNS. I plan to use the time gained through the funding of this grant to 1) increase my commitment to technical development of new in vivo electrochemical techniques that could be useful in aging research, 2) strengthen my existing research collaborations, and 3) to receive additional training from other laboratories to strengthen and expand my aging research program. With RCDA support, the University of Colorado will relieve me of my current clinical laboratory, administrative, and major teaching duties, such that I can concentrate on my scientific development. The research will utilize a rodent model (Fischer 344 rat) to assess age-related changes in dopaminergic inputs to the striatum and noradrenergic afferents to the cerebellum in intact animals. Following balance and coordination measurements in the young mature and aged animals, high-speed in vivo electrochemical methods (5- 25Hz) will be employed to quantitate the magnitude and temporal characteristics of potassium-evoked and electrically induced release of monoamines. Intracranial microdialysis will be employed as an alternative technique to investigate extracellular changes in monoamines and monoamine metabolites, to aid in the further validation of the electrochemical methods. High performance liquid chromatography coupled with electrochemical detection (HPLC-EC) will be used to measure whole tissue levels of monoamines and their metabolites, for correlation with the monoamine release data. Finally, in situ monoamine-containing brain cell transplants into adult hosts will be used as a model system to delineate possible intrinsic versus extrinsic determinants that may be associated with any age-related changes.

该RCDA建议涉及动态的调查 可能发生的含孤原传入的突触前变化 在大脑区域衰老期间，已知可以调节平衡和步态（即。 纹状体和小脑）。 在RCDA的支持下，我希望留在 医学院的学术环境，专注于与年龄有关的 中枢神经系统的单胺能系统的变化。 我打算使用 通过这笔赠款的资金到1）增加我的时间 致力于新体内电化学的技术发展 可能在衰老研究中有用的技术，2）加强 我现有的研究合作，以及3） 其他实验室的培训以加强和扩大我的衰老 研究计划。 在RCDA的支持下，科罗拉多大学将减轻我 我目前的临床实验室，行政和主要教学 职责，使我可以专注于我的科学发展。 该研究将利用啮齿动物模型（Fischer 344大鼠） 评估纹状体的多巴胺能输入的年龄相关变化 以及完整动物小脑的去甲肾上腺素能传入。 遵循年轻成熟的平衡和协调测量 和老化的动物，高速体内电化学方法（5- 25Hz）将用于定量尺寸和时间 钾诱发和电诱导的特征 单胺的释放。 颅内微透析将用于 作为研究细胞外变化的替代技术 在单胺和单胺代谢物中，以进一步帮助 电化学方法的验证。 高性能液体 色谱与电化学检测（HPLC-EC）结合 将用于测量单胺的整个组织水平及其 代谢物，与单胺释放数据相关。 最后，原位含单胺的脑细胞移植到 成人主持人将被用作模型系统来描述可能 可能与 任何与年龄有关的变化。