Using Photobiomodulation to Alleviate Brain Hypoperfusion in Alzheimer's Disease

利用光生物调节缓解阿尔茨海默氏病的大脑灌注不足

基本信息

批准号：
10656787
负责人：
Hung Wen (Kevin) Lin
金额：
$ 70.73万
依托单位：
LOUISIANA STATE UNIV HSC SHREVEPORT
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-05-15 至 2023-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10656787
关键词：
3xTg-AD mouse Age Alternative Therapies Alzheimer&apos s Disease Alzheimer&apos s disease brain Alzheimer&apos s disease model Alzheimer&apos s disease pathology Alzheimer&apos s disease related dementia Area Attenuated Blood - brain barrier anatomy Blood Vessels Brain Cell Adhesion Molecules Cerebrovascular Circulation Cerebrovascular Disorders Circulation Coupled Data Development Diameter Discrimination Disease Disease Progression Embryo Enzymes Extravasation Family Female Genetic Goals Human Immunity Impairment Inflammation Investigation Ischemia Knockout Mice Knowledge Laser Scanning Microscopy Laser Speckle Imaging Lasers Learning Leucocytic infiltrate Leukocyte Rolling Light Longevity Malignant Neoplasms Measures Mediating Memory Memory impairment Messenger RNA Methylation Modality Mus NOTCH1 gene Neurodegenerative Disorders Nitric Oxide Obesity Pathway interactions Patients Penetration Perfusion Persons Physical therapy Predictive Factor Protein Inhibition Protein-Arginine N-Methyltransferase Proteins Regulatory Element Risk Factors Rodent Model Role Severities Signal Transduction Stroke System Texture Therapeutic Tight Junctions Vascular Cognitive Impairment Vascular Dementia Vibrissae Woman aged behavioral outcome blood-brain barrier disruption blood-brain barrier permeabilization brain metabolism cerebral hypoperfusion cerebrovascular clinically relevant combat cranium functional improvement hypoperfusion improved innovation knock-down male men mouse model nervous system disorder neurovascular neurovascular coupling novel object recognition occludin pharmacologic photobiomodulation preservation prevent response sex two-photon

项目摘要

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.

项目摘要阿尔茨海默氏病是最常见和进行性遗传神经退行性疾病之一目前有超过500万人患有阿尔茨海默氏病的美国。知识的关键差距是血管脑灌注动力学如何参与血管痴呆。这个新兴和困难的领域查询对神经血管系统，大脑新兴网络的研究有限，只有间接的与神经疾病有关的应用，其中蛋白精氨酸甲基转移酶的功能作用它们与大脑代谢，循环，功能学习和记忆有关。在这里，我们试图研究蛋白质精氨酸甲基转移酶4作为重要年龄和与性别相关的脑调节元件延迟血管认知障碍。我们最近发现蛋白精氨酸甲基转移酶4是小鼠和人类的广告大脑中增强。我们的中心假设是抑制蛋白精氨酸甲基转移酶4通过光生物调节，一种非侵入性治疗（808 nm，35 mW/cm2），可以增强神经血管耦合，维持血脑屏障的完整性以及衰老的学习/记忆缺陷 3XTG-AD小鼠。因此，广告大脑中PRMT4的抑制可以恢复微血管灌注和下灌注介导的AD。这是一项多PI的建议，赢得了蛋白质凯文·林博士的优势精氨酸甲基转移酶专家在脑血管脑灌注方面（通过两光子激光扫描显微镜）在各种疾病状态（例如AD和中风/缺血）中，以及Quangang Zhang博士，专家与AD/ADRD相关的功能行为结果，具有光生调节的优势作为临床相关的治疗。