BDNF-mediated effects of rTMS on cognitive dysfunction in Veterans

在我们的退伍军人群体中，许多人，特别是越南时代的队列，患有痴呆症相关的 认知障碍预计这一数字将随着退伍军人年龄的增长而增加。发展中 有效的治疗策略是最重要的，因为这种损害给患者带来了巨大的负担。 退伍军人本身，他们的照顾者，以及退伍军人事务部的资源。重复 经颅磁刺激（rTMS）是一种很有前途的治疗策略，它利用电磁学 非侵入性地激活皮层细胞恢复认知功能据认为，这一过程 增加整个大脑的神经营养信号，并可能增加大脑的完整性， 对神经营养因子的损失敏感的结构，特别是那些在生长早期下降的结构。 Alzhiemer's disease（AD） 这项提案旨在提高我们对认知能力下降的神经化学的理解， 随后，使用人类和动物模型从rTMS治疗中康复。我们将评估 脑源性神经营养因子（BDNF）作为AD的结果的变化以及如何 rTMS处理影响BDNF信号传导。这一措施的作用将与认知 在人类和小鼠中的表现。我们将首先评估BDNF信号传导的变化程度， AD小鼠模型，然后我们将实施小鼠rTMS系统，以增加 这些老鼠该系统将用于测试AD患者认知功能变化的脑神经化学。 利用小鼠模型将使我们能够全面研究神经化学在一个受控的 实验设置具体来说，我们将测量小鼠BDNF信号通路的改变， rTMS处理的和对照小鼠的AD模型。我们还将确定rTMS是否可用于 通过提供长期治疗，并测量生物化学和免疫学指标， 变化和认知表现。最后，BDNF将在来自人类的血液样本中进行测量， 用rTMS或假手术治疗的认知障碍，以便将生物化学与 人类认知功能障碍急性脑梗死患者脑脊液和血浆中关键蛋白的初步研究 人类将为认知生物化学未来的资助机会铺平道路。 这一提议的结果将为认知功能障碍的生化机制提供有价值的见解。 下降这项研究还将确定与认知能力相关的关键生物标志物， 作为治疗结果的具体指标。生物化学和认知的结合 对人类和动物的测量提供了一种创新的、多方面的方法， 直接转化为我们退伍军人的医疗服务。

Many individuals in our Veteran population, especially the Vietnam era cohort, suffer from dementia-related cognitive impairment. This number is expected to increase as the population of Veterans age. Developing effective treatment strategies is of the upmost importance, as this impairment places a huge burden on the Veterans themselves, their caregivers, and the resources of the Department of Veterans Affairs. Repetitive transcranial magenetic stimulation (rTMS) is a promising treatment strategy, that utilizes electromagnetics to noninvasively activate cortical cells and restore cognitive functioning. It is thought that this process increases neurotrophic signaling throughout the brain, and could potentially increase the integrity of brain structures sensitive to a loss in neurotrophic factors, especially those structures that declince early in the course of Alzhiemer's disease (AD). This proposal aims to improve our understanding of the neurochemistry of cognitive decline, and subsequently, rehabilitation from rTMS treatment using both human and animal models. We will assess changes in the neurotrophic factor Brain-Derived Neurotrophic Factor (BDNF) as a result of AD and how rTMS treatment influences BDNF signaling. The role of this measure will be related to cognitive performance in both humans and mice. We will first assess the extent of changes in BDNF signaling in a mouse model of AD, and then we will implement an rTMS system for mice to increase BDNF in the brains of these mice. This system will be used to test the brain neurochemistry of changes in cognitive function in AD. Utilization of a mouse model will allow us to comprehensively investigate neurochemistry in a controlled experimental settting. Specifically, we will measure alterations in the signaling pathway of BDNF in a mouse model of AD for both rTMS-treated and control mice. We will also determine if rTMS can be utilized to prevent AD pathology in these mice by providing long-term treatment, and measuring both biochemical changes and cognitive performance. Finally, BDNF will be measured in blood samples from humans with cognitive impairment either treated with rTMS or a sham in order to related biochemistry to changes in human cognitive dysfunction. Exploratory research on key proteins from cerebral spinal fluid and plasma in humans will pave the way for future funding opportunities in the biochemistry of cognition. Results from this proposal will provide valuable insight into the biochemical mechanisms of cognitive decline. This research will also identify key biomarkers that can be related to cognitive performance and be utilized as concrete measures of treatment outcome. The combination of biochemical and cognitive measurements on both humans and animals provides an innovative, multi-faceted approach that can be directly translated into medical treatments for our Veterans.