Primate model of deep brain stimulation for Alzheimers and age-related cognitivedecline

阿尔茨海默病和与年龄相关的认知衰退的深部脑刺激灵长类动物模型

• 批准号: 10399701
• 负责人: David T Blake
• 金额: $ 298.14万
• 依托单位: VANDERBILT UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-02-01 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10399701
• 关键词: Primate; model; deep; brain; stimulation

PROJECT SUMMARY This project will investigate the potential of deep brain stimulation to improve cognitive abilities in aging, and counteract the effects of Alzheimer's and other types of dementias. We will perform experiments in nonhuman primates, because they experience a similar age-related cognitive decline as humans. Stimulation will be applied in the Nucleus Basalis of Meynert, the sole source of acetylcholine to neocortex. Drawing from recent experiments showing success of this method, intermittent stimulation will be delivered at 60 pulses per second for 20 seconds of each minute in old monkeys. The study design will test the efficacy of stimulation, and the duration of benefits after the intervention. Use of complementary pharmacological agents will determine if short-term effects of stimulation on cognition may be augmented by other agents, and what pharmacological systems they interact with. Partial nicotinic acetylcholine receptor agonists, positive allosteric modulators, serotonergic and noradrenergic agents will be tested, as will other agents that interact with cholinesterase inhibitors. In addition, the project will determine whether deep brain stimulation can ameliorate pathological changes associated with Alzheimer's dementias, as noted by biochemical, metabolic, and brain structural measures.

项目摘要 该项目将研究脑深部电刺激改善衰老认知能力的潜力， 抵消阿尔茨海默氏症和其他类型痴呆症的影响。我们将在非人类身上进行实验 灵长类动物，因为他们经历了与人类相似的与年龄相关的认知能力下降。刺激会被 应用于Meynert基底核，这是新皮质乙酰胆碱的唯一来源。图为最近 实验表明这种方法是成功的，间歇刺激将以每秒60个脉冲的速度传递 每分钟20秒。研究设计将测试刺激的功效， 干预后的受益时间。使用补充药理学药物将确定是否 刺激对认知的短期影响可能会被其他药物所增强， 与之互动的系统。部分烟碱乙酰胆碱受体激动剂，正变构调节剂， 将测试肾上腺素能和去甲肾上腺素能药物，以及与胆碱酯酶相互作用的其他药物 抑制剂的此外，该项目将确定深部脑刺激是否可以改善病理性 与阿尔茨海默氏痴呆症相关的变化，如生化，代谢和脑结构所示 措施