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

项目总结 该项目将研究脑深部刺激在提高老年人认知能力方面的潜力，以及 抵消阿尔茨海默氏症和其他类型的痴呆症的影响。我们将在非人类身上进行实验 灵长类动物，因为它们经历了与人类相似的与年龄相关的认知衰退。刺激将是 应用于Meynert基底核，这是新皮质乙酰胆碱的唯一来源。从最近绘制 实验表明，这种方法是成功的，间歇刺激将以每秒60个脉冲的速度提供 在老猴子身上每分钟20秒。这项研究设计将测试刺激的效果，以及 干预后的福利期限。补充药理药物的使用将决定是否 刺激对认知的短期影响可能会被其他药物增强，哪些药理作用？ 它们与之交互的系统。部分烟碱型乙酰胆碱受体激动剂，阳性变构调节剂， 将测试5-羟色胺能药和去甲肾上腺素能药，以及其他与胆碱酯酶相互作用的药。 抑制剂。此外，该项目还将确定脑深部刺激是否能改善病理 与阿尔茨海默病痴呆相关的变化，如生化、代谢和脑结构 措施。

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.