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Time restricted feeding rescues circadian and motor dysfunction in a mouse model of Huntington's disease

限时喂养可挽救亨廷顿病小鼠模型的昼夜节律和运动功能障碍

基本信息

批准号：
10261774
负责人：
CHRISTOPHER SCOTT COLWELL
金额：
$ 12.44万
依托单位：
UNIVERSITY OF CALIFORNIA LOS ANGELES
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-12-01 至 2021-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10261774
关键词：
Anatomy Animals Behavioral Brain Brain region Calcium Caring Cell Death Cells Circadian Dysregulation Circadian Rhythms Corpus striatum structure Development Disease Management Disease Progression Drosophila genus Drowsiness Eating Electrodes Electroencephalography Electrophysiology (science)Exhibits Family member Fasting Frequencies Gills Head Homeostasis Human Huntington Disease Impaired cognition Individual Knowledge Life Measurement Measures Methods Microscope Modeling Motor Motor Cortex Mus Mutation Names Neurodegenerative Disorders Neurons Optics Pathology Patients Pattern Performance Phase Polysomnography Process Property Protocols documentation Quality of life Recovery Reporter Schedule Signal Transduction Sleep Sleep Deprivation Sleep Stages Sleep Wake Cycle Sleep disturbances Slow-Wave Sleep Source Specificity Testing Time-restricted feeding Wakefulness Work awake experience experimental study feeding improved motor disorder mouse model mutant open source protein aggregation response restoration sleep behavior sleep difficulty sleep onset sleep pattern sleep quality therapy design tool treatment strategy vigilance

项目摘要

Disturbances in the daily sleep-wake cycle are a common feature experienced by individuals with neurodegenerative disorders. They have difficulty sleeping at night and staying awake during the day. These disturbances have a major impact on their quality of life as well as on the family members who care for them. Huntington's disease (HD) is the most common genetically determined neurodegenerative disease and we have documented that circadian rhythms are disrupted early in the disease progression in three distinct mouse models of HD. Using a mouse model of HD which expresses the human mutation (BACHD), we have successfully improved the behavioral and some of the autonomic deficits using a protocol that limits the daily food intake into a 6-hr window during the animal's active phase, and is thus named: time restricted feeding (TRF). This feeding/fasting cycle improved behaviorally defined sleep in the BACHD model when applied early in disease progression. To our knowledge, this is the first demonstration that TRF can improve sleep parameters in mice although earlier work has shown that a similar schedule can improve behavioral sleep patterns in Drosophila. A critical gap in our knowledge is whether TRF specifically alters the temporal pattern of sleep stages, sleep homeostasis or cortical up/down states reflecting slow wave activity. This proposal will employ electrophysiological and optical approaches to close this gap and determine if such treatments can be usefully employed in HD. Given the shared pathology including the formation of protein aggregates and cell death, treatment strategies that prove to be effective in HD are likely to be broadly beneficial in the management of neurodegenerative diseases.

日常睡眠-觉醒周期紊乱是糖尿病患者的常见特征