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

迈纳特基底核的深部脑刺激：刺激参数在神经发生和认知恢复中的作用

• 批准号: 10354896
• 负责人: Deepak Kumbhare
• 金额: --
• 依托单位: VIRGINIA COMMONWEALTH UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-02-01 至 2022-05-15
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10354896
• 关键词: Adverse effects; Alzheimer' s Disease; Amyloid; Animal Model; Animals; Anterior; Anxiety; Arousal; Attention; Auditory; Basal Nucleus of Meynert; Cathodes; Cell Nucleus; Cells; Clinical; Clinical Treatment; Clinical Trials; Cognition; Cognitive; Data; Deep Brain Stimulation; Dementia; Diffuse; Disease; Economics; Electric Stimulation; Evaluation; Future; Goals; Health; Histologic; Hour; Immunoglobulin G; Individual; Learning; Lesion; Lewy Body Dementia; Lobar; Maintenance; Measures; Medial; Memory; Modeling; Modification; Monitor; Neocortex; Nerve Regeneration; Neuronal Differentiation; Nucleus Accumbens; Outcome; Parkinson' s Dementia; Persons; Play; Population; Prefrontal Cortex; Proteins; REM Sleep; Rattus; Residual state; Rest; Role; Sleep; Sleep Wake Cycle; Sleep disturbances; Stress; Toxin; Wakefulness; Work; awake; base; behavioral outcome; biological adaptation to stress; cerebral atrophy; cholinergic; cognitive process; cognitive recovery; cognitive testing; deep brain stimulator; demented; design; early phase clinical trial; effective therapy; electric field; entorhinal cortex; field study; improved; innovation; migration; mild cognitive impairment; nerve stem cell; neuroblast; neurogenesis; neurorestoration; novel; pilot trial; preservation; prevent; response; simulation; social; subventricular zone; treatment strategy; vigilance

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.

项目总结 患有痴呆症的人数每五年翻一番，创造了一个不断增长的健康、社会、 以及未来的经济灾难。目前还没有治疗痴呆症的有效方法。痴呆症 由于阿尔茨海默病、路易体痴呆和帕金森氏病痴呆与 Meynert(NBM)基底核变性。这会导致胆碱能供应的丧失。 大脑皮层萎缩，以及与大脑皮层相关的各种能力的丧失。提供的潜力 在早期的临床试验中，通过电刺激NBM来缓解症状已经被认可。 正在进行中。另一方面，NBM深部脑刺激(DBS)改变脑血管紧张素转换酶活性的可能性 尽管有多种证据表明，通过刺激诱导神经发生引起的疾病尚未得到评估。 演示刺激在其他结构中诱导神经发生。我们已经在我们的 初步数据。这项提议的目标是描述和优化这一潜力。为此，我们将 评估与持续NBM相关的神经再生效应和认知改善 刺激痴呆大鼠和对照大鼠，监测对睡眠-觉醒周期和压力的不利影响。 由于NBM在睡眠中扮演的角色，以及总是保持警惕和警惕的潜在压力，我们 将评估“依赖活动的刺激”作为优化NBM积极效果的替代策略 对动物的神经发生、学习和健康的刺激。疾病的最佳参数 改进将对未来NBM刺激临床试验的设计具有重要意义。