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.

胆碱能毒蕈碱受体的破坏会在注意力，记忆习得和记忆巩固方面产生一系列深刻的缺陷。同样，阿尔茨海默氏病和正常衰老的认知能力下降与胆碱能功能障碍有关。 M1受体已成为记忆缺陷的药理治疗的重点，也许是因为它是海马和皮质中分布最广泛的毒蕈碱受体。在这里，我们研究了我们在M1中发现的选择性认知缺陷的相关性 敲除小鼠的衰老认知能力下降。在特定的目标1中，我们扩展了M1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M1Knockout和老年小鼠是否具有认知中的任何缺陷。最终，在AIM 3中，我们建立了一个衰老突变体和野生型M1小鼠的菌落。据预测，M1突变体将显示衰老的过早下降。具体来说，没有产生认知缺陷的M1杂合缺失可能会开始以衰老的形式表现出来。这些研究将构成研究M1受体与衰老认知能力下降的相关性的基础。