Using Photobiomodulation to Alleviate Brain Hypoperfusion in Alzheimer's Disease

项目摘要 阿尔茨海默病是一种最常见和进行性的遗传性神经退行性疾病， 美国目前有超过500万人患有阿尔茨海默病。知识的一个关键差距是 血管性痴呆与脑血管灌注动力学的关系这一新兴而困难的领域， 调查有限的调查，神经血管系统，脑紧急网络，只有间接的 涉及神经疾病的应用，其中蛋白质精氨酸甲基转移酶作为 它们与脑代谢、循环、功能性学习和记忆有关，但研究不足。在此，我们寻求 研究蛋白质精氨酸甲基转移酶4作为重要年龄和性别相关的脑调节元件， 延迟血管性认知障碍。我们最近发现蛋白质精氨酸甲基转移酶4是 在小鼠和人类的AD大脑中增强。我们的中心假设是蛋白质精氨酸的抑制 甲基转移酶4通过光生物调节，一种非侵入性治疗（808 nm，35 mW/cm 2），可以增强 神经血管耦合，维持血脑屏障的完整性，并减轻老年人的学习/记忆缺陷 3xTg-AD小鼠。因此，抑制AD脑中的PRMT 4可以恢复微血管灌注， 低灌注介导的AD。这是一个多PI的建议，获得博士的优势凯文林，蛋白质 精氨酸甲基转移酶在脑血管脑灌注中的专家（通过双光子激光扫描 显微镜）在各种疾病状态如AD和中风/缺血中的应用， 与AD/ADRD相关的功能行为结局，光生物调节的强度作为临床相关 疗法

Project Summary Alzheimer's disease is one of the most common and progressive genetic neurodegenerative disorders in the US with more than 5 million people currently living with Alzheimer's disease. A critical gap in knowledge is how vascular brain perfusion dynamics are involved in vascular dementia. This emerging and difficult area of inquiry has limited investigations into the neurovascular system, brain emergent networks, with only indirect applications related to neurological diseases, where the functional role of protein arginine methyltransferases as they relate to brain metabolism, circulation, functional learning and memory are understudied. Here, we seek to investigate protein arginine methyltransferase 4 as an important age and sex-related brain regulatory element to delay vascular cognitive impairment disorders. We recently discovered protein arginine methyltransferase 4 was enhanced in the AD brain in mice and humans. Our central hypothesis is the inhibition of protein arginine methyltransferase 4 via photobiomodulation, a non-invasive therapeutic (808 nm, 35 mW/cm2), can enhance neurovascular coupling, maintain blood-brain-barrier integrity, and attenuate learning/memory deficits in aged 3xTg-AD mice. Therefore, inhibition of PRMT4 in the AD brain can revive microvessel perfusion and hypoperfusion-mediated AD. This is a multi-PI proposal garnering the strengths of Dr. Kevin Lin, a protein arginine methyltransferase expert in cerebral vascular brain perfusion (via two-photon laser scanning microscopy) in various disease states such as AD and stroke/ischemia, and Dr. Quanguang Zhang, an expert in functional behavior outcomes related to AD/ADRD with strengths in photobiomodulation as a clinically relevant therapy.