Deep brain stimulation of the Nucleus Basalis of Meynert: the role of stimulation parameters in neurogenesis and cognitive recovery.

项目摘要 痴呆症患者的数量每五年翻一番，创造了一个不断增长的健康，社会， 以及未来的经济灾难。目前还没有有效的治疗痴呆症的方法。痴呆 由于阿尔茨海默病、路易体痴呆和帕金森病， Meynert基底核变性（NBM）。这会导致对脑的胆碱能供应丧失， 皮质，皮质萎缩，以及与皮质相关的各种能力的丧失。可能提供 早期的临床试验已经认识到，通过电刺激NBM可以缓解症状 正在进行中另一方面，NBM脑深部电刺激（DBS）改变脑缺血过程的可能性也很小。 尽管有多方面的证据，但尚未对通过刺激诱导神经发生的疾病进行评估 这表明在其他结构中刺激诱导神经发生。我们已经证明了这种潜力， 初步数据。本提案的目的是使这种潜力得到充分发挥。为此，我们将 评估与连续NBM相关的神经再生作用和认知改善 并监测对睡眠-觉醒周期和压力不利影响。 由于NBM在睡眠中的作用以及始终保持警觉和警惕的潜在压力，我们 将评估“活动依赖性刺激”作为优化NBM积极作用的替代策略 刺激动物的神经发生、学习和健康。疾病的最佳参数 修改对于NBM刺激的未来临床试验的设计将是重要的。

PROJECT SUMMARY The number of people living with dementia doubles every five years, creating an ever-growing health, social, and economic catastrophe for the future. There are currently no effective treatments for dementia. Dementia due to Alzheimers disease, Lewy Body dementia, and Parkinsons Disease dementia is associated with degeneration of the nucleus basalis if Meynert (NBM). This results in the loss of the cholinergic supply to the cortex, cortical atrophy, and the loss of a variety of abilities associated with that cortex. The potential to provide symptomatic relief through the electrical stimulation of the NBM has been recognized, with early clinical trials underway. On the other hand, the potential for NBM deep brain stimulation (DBS) to modify the course of the disease through stimulation induced neurogenesis has not been evaluated, despite multiple lines of evidence demonstrating stimulation induced neurogenesis in other stuctures. We have demonstrated this potential in our preliminary data. The goal of this proposal is charcterize and optimize this potential. To this end we will evaluate the neuroregenerative effects and cognitive improvements associated with continuous NBM stimulation in demented and control rats and monitor for adverse effects on sleep-wake cycles and stress. Because of the role that the NBM plays in sleep and the potential stress of always being alert and vigilant, we will evaluate ‘activity-dependent stimulation’ as an alternative strategy to optimize the positive effects of NBM stimulation on neurogenesis, learning, and health of the animal. The optimal parameters for disease modification will be important for the design of future clinical trials of NBM stimulation.