A Novel M1 muscarinic activator to treat memory deficits in Alzheimer's Disease

描述(由申请人提供)：当前项目的目标是开发新的药物疗法来治疗与阿尔茨海默病相关的认知功能障碍。其目标是治疗记忆障碍等症状，但也要推迟导致认知能力下降的大脑功能障碍的发生。拟议的实验旨在证明一种新的毒鼠碱M1特异性激动剂(VU0364572)在治疗阿尔茨海默病大鼠模型中的海马区功能障碍的疗效。该方法将重点放在体内对许多单个海马神经元的电生理记录，作为记忆功能的灵敏测试。此外，拟议的实验旨在证明VU0364572在延缓阿尔茨海默病大鼠模型记忆障碍和脑病理发生方面的有效性。在两年的时间里，拟议的实验预计将有助于培养一名研究生和两名本科生。

DESCRIPTION (provided by applicant): The objective of the current project is to develop new drug therapies to treat cognitive dysfunction associated with Alzheimer's disease. The goal is to treat symptoms such as memory impairment but also to delay the onset of the brain dysfunction that underlies this cognitive decline. The proposed experiments aim to demonstrate the efficacy of a novel muscarinic M1-specific agonist (VU0364572) in treating hippocampal dysfunction in a rat model of Alzheimer's disease. The approach will focus on in vivo electrophysiological recordings of many individual hippocampal neurons as a sensitive assay of memory functioning. In addition, the proposed experiments aim to demonstrate the efficacy of VU0364572 in delaying the onset of memory impairments and brain pathology in a rat model of Alzheimer's disease. Over the two- year period, the proposed experiments are expected to contribute to the training of one graduate student and two undergraduate students.