GLUTAMATE RECEPTOR PROCESSING IN AGING

老化过程中的谷氨酸受体加工

• 批准号: 2002397
• 负责人: Noel G. Carlson
• 金额: $ 7.45万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-03-01 至 1999-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2002397
• 关键词: Animalia; RNA splicing; aging; glutamate receptor; messenger RNA; protein biosynthesis; receptor expression; tissue /cell culture

Among the many receptor types implicated in age-related alterations of normal neurotransmission are the fast excitatory glutamate-activated cationic channel receptors (GLuR). Since these receptors are thought to play a central role in establishing and maintaining optimal cognitive function, and the aberrant expression or regulation of these receptors has been implicated in neuronal damage, understanding the mechanisms that regulate their expression is central to determining how these receptors may participate in age-related changes in the brain. One way GluR function can be regulated is through alternative splicing and RNA editing of subunit transcript. This imparts significantly differently functional properties upon the mature receptor. In this one-year R03 proposal, I will examine GluR subunit RNA editing and/or splicing from various brain regions of young, adult and aged mice to test the following hypothesis. Specific Aim 1. Alternative Splicing of Glutamate Receptor Subunits in the Aging Brain. The hypothesis to be tested is: The relative of alternatively spliced transcripts of GluR1, GluR2, GluR3, GluR4 is altered in the aged mouse brain relative to young or adult mice. Specific Aim 2. RNA editing of Non-NMDA Glutamate Receptor Subunits in the Aging Brain. The hypothesis to be tested is: The relative ratio of edited versus non-edited GluR2, GluR5, or GluR6 is altered in the aged mouse brain relative to young or adult mice.

在许多与年龄相关的变化有关的受体类型中， 正常的神经传递是快速兴奋性谷氨酸激活的 阳离子通道受体（GLuR）。 因为这些受体被认为 在建立和维持最佳认知能力方面发挥核心作用 功能，这些受体的异常表达或调节 与神经元损伤有关，了解 调节它们的表达是决定这些受体如何 参与大脑中与年龄相关的变化。 GluR功能可以 是通过选择性剪接和RNA编辑亚基 文字记录。 这赋予了显著不同的功能特性 成熟的受体。 在这份为期一年的R 03提案中，我将研究 GluR亚单位RNA编辑和/或剪接来自不同的脑区域， 年轻、成年和老年小鼠来测试以下假设。 具体目标1. 谷氨酸受体亚基在细胞内的选择性剪接 大脑老化 要检验的假设是： GluR 1、GluR 2、GluR 3、GluR 4的剪接转录本在老年人中发生改变， 小鼠大脑相对于年轻或成年小鼠的相对大小。 具体目标2。 非NMDA谷氨酸受体亚单位在脑内的RNA编辑 大脑老化要检验的假设是：编辑的相对比率 与未编辑的GluR 2、GluR 5或GluR 6相比， 相对于年轻或成年小鼠。