ROLE OF CHOLINERGIC M1 RECEPTOR IN MEMORY AND COGNITION

胆碱能 M1 受体在记忆和认知中的作用

• 批准号: 6840155
• 负责人: STEPHAN G ANAGNOSTARAS
• 金额: $ 4.55万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-05-01 至 2005-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6840155
• 关键词: age difference; aging; cognition; genetically modified animals; laboratory mouse; memory; muscarinic receptor; phenotype; protein structure function

Disruption of cholinergic muscarinic receptors produces an array of profound deficits in attention, memory acquisition, and memory consolidation. Likewise, cognitive decline in Alzheimer's disease and in normal aging is associated with cholinergic dysfunction. The M1receptor has become a focus of pharmacological treatment for memory deficits, perhaps because it is the most widely distributed muscarinic receptor in the hippocampus and cortex. Here we examine the relevance of selective cognitive deficits we have found in M1 knockout mice to cognitive decline in aging. In specific aim 1, we extend the cognitive phenotype of the M1 knockout. We then compare this phenotype to normal aged mice in aim 2, in order to determine if the young M1knockout and aged mouse share any deficits in cognition. Finally in aim 3, we establish a colony of aging mutant and wildtype M1 mice. It is predicted that M1 mutants will show premature further decline in aging. Specifically the M1 heterozygous deletion, which does not produce cognitive deficits, may begin to exhibit them with aging. These studies will form the basis for an investigation of the relevance of the M1 receptor to cognitive decline in aging.

胆碱能毒碱受体的破坏会在注意力、记忆获得和记忆巩固方面产生一系列严重的缺陷。同样，阿尔茨海默病和正常衰老的认知能力下降与胆碱能功能障碍有关。M1受体已经成为治疗记忆缺陷的药物治疗的焦点，可能是因为它是在海马体和皮质中分布最广泛的M受体。在这里，我们检查了我们在M1中发现的选择性认知缺陷的相关性 基因敲除小鼠在衰老过程中认知能力下降。在具体目标1中，我们扩展了M1基因敲除的认知表型。然后，我们将这种表型与AIM 2中的正常老年小鼠进行比较，以确定年轻的M1基因敲除小鼠和老年小鼠是否存在任何认知缺陷。最后，在目标3中，我们建立了一个老化突变和野生型M1小鼠群体。据预测，M1突变体将在衰老过程中出现过早的进一步衰退。具体地说，M1杂合性缺失不会产生认知缺陷，可能会随着年龄的增长而开始表现出这些缺陷。这些研究将为研究M1受体与衰老中认知功能衰退的相关性奠定基础。