GLUTAMATE RECEPTOR PROCESSING IN AGING

在与年龄相关的改变有关的许多受体类型中 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）。 由于这些受体被认为 在建立和维持最佳认知方面发挥核心作用 功能，并且这些受体的异常表达或调节 与神经元损伤有关，了解其机制 调节它们的表达对于确定这些受体如何发挥作用至关重要 参与大脑中与年龄相关的变化。 GluR 函数的一种方式 通过亚基的选择性剪接和RNA编辑来调节 成绩单。 这赋予了显着不同的功能特性 成熟受体上。 在这个为期一年的 R03 提案中，我将研究 来自不同大脑区域的 GluR 亚基 RNA 编辑和/或剪接 年轻、成年和老年小鼠来检验以下假设。 具体目标 1. 谷氨酸受体亚基的选择性剪接 大脑老化。 要检验的假设是： 的相对值 GluR1、GluR2、GluR3、GluR4 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。 具体目标 2. 非 NMDA 谷氨酸受体亚基的 RNA 编辑 大脑老化。要检验的假设是： 编辑后的相对比例 与未编辑的 GluR2、GluR5 或 GluR6 相比，衰老小鼠大脑中的 GluR2、GluR5 或 GluR6 发生了改变 相对于年轻或成年小鼠。

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.