Retinal Determinants of Circadian Function and Sleep-Wake Cycles in Parkinson's Disease

帕金森病昼夜节律功能和睡眠-觉醒周期的视网膜决定因素

基本信息

  • 批准号:
    10735341
  • 负责人:
  • 金额:
    $ 63.37万
  • 依托单位:
  • 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:
    2023-09-01 至 2028-05-31
  • 项目状态:
    未结题

项目摘要

Project Summary Disrupted sleep and daytime sleepiness are among the most common non-motor symptoms (NMS) of Parkinson’s disease (PD). Mechanisms underlying these symptoms are not well understood, and treatment options remain limited. The endogenous human circadian system, which is most effectively synchronized by ocular light exposure, has a critical role in regulating sleep and sleepiness. Our investigations in patients with PD revealed: (i) blunting of the circadian rhythm of melatonin, a well-established marker of circadian rhythms; (ii) changes in circadian timing (“phase”) of clock gene expression; and (iii) beneficial effects of bright light therapy, a circadian-based intervention, on sleep and wake consolidation. In this project, we propose to expand this line of investigation and examine melanopsin-expressing intrinsically photosensitive Retinal Ganglion Cells (ipRGC) across the continuum of PD. The ipRGC give origin to the retinohypothalamic tract through which they project light stimuli to the central circadian pacemaker and synchronize circadian rhythms to external light, thus affecting circadian and sleep behavior. A recently proposed surrogate marker of melanopsin function in humans is the post-illumination pupil response (PIPR) obtained using non-invasive chromatic pupillometry. To quantify the relationships among ipRGC function, circadian rhythms, sleep, and sleepiness, we will study four groups of participants: (i) advanced PD (n=20), (ii) de-novo, drug-naïve PD (n=20), (iii) REM Sleep Behavior Disorder, which represents a prodromal stage of an evolving synucleinopathy, such as PD (n=20), and (iv) healthy controls (HC) (n=20). After the screening, participants will wear an actiwatch for continuous activity monitoring and keep daily sleep diaries during a 14-day baseline period. Participants will undergo pupillometry and complete questionnaires about sleep and sleepiness, and a subset will undergo Dopamine Transporter SPECT Imaging to quantify nigrostriatal denervation. Participants will be subsequently admitted for inpatient assessment of circadian markers, sleep, and sleepiness, including overnight polysomnography, followed by multiple sleep latency testing and a 24-hour Circadian Protocol for blood sampling for melatonin measurements. Aim 1 will test if melanopsin-dependent retinal phototransduction is altered across the continuum of PD compared with HC. Aims 2 and 3 will test the hypothesis that melanopsin-dependent retinal phototransduction is correlated with circadian amplitude and sleep and/or sleepiness across the continuum of PD compared with HC. Exploratory Aim 4 will examine associations between melanopsin-dependent retinal phototransduction and imaging metrics of the nigrostriatal dopaminergic system. Participants enrolled in years 1-3 will undergo a two- year follow-up pupillometry, actigraphy, and sleep/sleepiness assessment. Short-term, the project will provide a foundation for investigations of retinal/melanopsin physiology in regulating sleep, sleepiness, and other NMS in PD. Long-term, the work will advance the development of novel circadian-based interventions aimed at retinal degeneration in PD, such as photoreceptor-specific light therapy or melanopsin gene therapy.
项目总结

项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

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Aleksandar Videnovic其他文献

Aleksandar Videnovic的其他文献

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{{ truncateString('Aleksandar Videnovic', 18)}}的其他基金

NAPS2 Recruitment, Education, and Outreach Core
NAPS2 招聘、教育和外展核心
  • 批准号:
    10457864
  • 财政年份:
    2021
  • 资助金额:
    $ 63.37万
  • 项目类别:
NAPS2 Recruitment, Education, and Outreach Core
NAPS2 招聘、教育和外展核心
  • 批准号:
    10187090
  • 财政年份:
    2021
  • 资助金额:
    $ 63.37万
  • 项目类别:
NAPS2 Recruitment, Education, and Outreach Core
NAPS2 招聘、教育和外展核心
  • 批准号:
    10674058
  • 财政年份:
    2021
  • 资助金额:
    $ 63.37万
  • 项目类别:
A Dose Selection Trial of Light Therapy for Impaired Sleep in Parkinson's Disease
光疗法治疗帕金森病睡眠障碍的剂量选择试验
  • 批准号:
    10012951
  • 财政年份:
    2019
  • 资助金额:
    $ 63.37万
  • 项目类别:
A Dose Selection Trial of Light Therapy for Impaired Sleep in Parkinson's Disease
光疗法治疗帕金森病睡眠障碍的剂量选择试验
  • 批准号:
    10208984
  • 财政年份:
    2019
  • 资助金额:
    $ 63.37万
  • 项目类别:
Bright light modulation of non-motor symptoms in Parkinson's disease
帕金森病非运动症状的亮光调节
  • 批准号:
    10054198
  • 财政年份:
    2016
  • 资助金额:
    $ 63.37万
  • 项目类别:
Circadian Rhythms and Sleep-Wake Cycles in Parkinson's Disease
帕金森病的昼夜节律和睡眠-觉醒周期
  • 批准号:
    9068250
  • 财政年份:
    2012
  • 资助金额:
    $ 63.37万
  • 项目类别:
Circadian Rhythms and Sleep-Wake Cycles in Parkinson's Disease
帕金森病的昼夜节律和睡眠-觉醒周期
  • 批准号:
    8664946
  • 财政年份:
    2012
  • 资助金额:
    $ 63.37万
  • 项目类别:
Circadian Rhythms and Sleep-Wake Cycles in Parkinson's Disease
帕金森病的昼夜节律和睡眠-觉醒周期
  • 批准号:
    8299875
  • 财政年份:
    2012
  • 资助金额:
    $ 63.37万
  • 项目类别:
Circadian Rhythms and Sleep-Wake Cycles in Parkinson's Disease
帕金森病的昼夜节律和睡眠-觉醒周期
  • 批准号:
    8730404
  • 财政年份:
    2012
  • 资助金额:
    $ 63.37万
  • 项目类别:
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