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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.

项目总结