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，同时也是为了延迟导致认知能力下降的大脑功能障碍的发作。拟议的实验旨在证明一种新的毒蕈碱M1特异性激动剂（VU0364572）在治疗阿尔茨海默病大鼠模型海马功能障碍的疗效。该方法将集中在许多个体海马神经元的体内电生理记录作为记忆功能的灵敏测定。此外，所提出的实验旨在证明VU0364572在阿尔茨海默病大鼠模型中延迟记忆障碍和脑病理学发作的功效。在两年内，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.