Newton001 SLEEP DEPRIVATION IN PARKINSON'S DISEASE: BRAZIL AND UNITED KINGDOM RESEARCH NETWORK

该项目旨在解决帕金森病（PD）的睡眠障碍这一重要问题，这在巴西是一个日益严重的健康问题，因为几十年来预期寿命显著增加（1970年：58.9岁；1980年：62.8岁；1990年：66.6岁；2011年：74.3岁——世界卫生排名），帕金森病影响65岁以上人口的1-3%。在发展中国家，神经退行性疾病的患病率正在上升，巴西的患病率估计为5.3%。此外，经济发展与城市化和轮班工作的增加有关，这对睡眠质量产生了负面影响，产生了一些健康问题（例如肥胖、癌症发病率升高、心血管和代谢紊乱），并增加了对公共卫生系统的需求。因此，该项目旨在解决巴西的一个战略性健康问题，并将建立一个科学的巴西-英国网络，用新颖的、最先进的分析工具和方法研究PD的基本机制。该项目的总体目标是研究PD动物模型中睡眠限制后的行为，神经化学和代谢变化。我们假设睡眠不足会导致认知缺陷、神经化学和代谢紊乱。行为和神经化学实验将在神经生理学实验室（帕拉纳联邦大学Lima和Louzada教授）进行，该实验室是巴西研究帕金森病的卓越中心。样品将通过靶向液相色谱/质谱（LC/MS）代谢组学（斯基恩教授（萨里大学））进行分析。额外的附加价值将通过采用第二个代谢组学平台，非靶向1H NMR代谢组学来表征大鼠模型中脑，血浆和尿液代谢物的变化（Swann博士，雷丁大学）。两种互补分析方法的应用确保了广泛的代谢组覆盖范围，并且使用多种样本类型可以在不同水平上研究PD中睡眠剥夺引起的代谢扰动。行为、神经化学和代谢组学方法的计划结合将使循环和中枢神经元参数的多角度观察成为可能，从而识别PD早期神经退行性变的可能分子生物标志物，具有潜在的诊断价值。英国和巴西之间还将进行研究人员和研究生的相互交流，以分享新的想法、技术和方法，从而实现共同（全球）增长。本实验的结果将有助于进一步了解PD的机制及其与睡眠/觉醒加工的相互关系。建立一个巴西-英国研究网络也将为未来的研究和合作提供基础。

The project aims to address the important topic of sleep disturbances in Parkinson's disease (PD) which is a growing health issue in Brazil, since life expectancy is significantly increasing across the decades (1970: 58.9 years; 1980: 62.8 years; 1990: 66.6 years; 2011: 74.3 years - World Health Rankings) and PD affects 1-3% of people over 65 years. Prevalence of neurodegenerative diseases is increasing in developing countries, in Brazil this is estimated to be 5.3%. In addition, economic development is associated with increased urbanization and shift work, which negatively impacts on sleep quality, generating several health problems (e.g. obesity, higher incidence of cancer, cardiovascular and metabolic disturbances) and increasing demand on the public health system. This project thus aims to address a strategic health problem in Brazil and will create a scientific Brazil-UK network to study the basic mechanisms underlying PD with novel, state-of-the-art analytical tools and approaches. The overall aim of the project is to investigate the behavioural, neurochemical and metabolic changes following sleep restriction in an animal model of PD. We hypothesise that sleep deprivation will produce cognitive deficits, neurochemical and metabolic disruption. The behavioural and neurochemical experiments will be undertaken in the Neurophysiology Laboratory (Profs Lima and Louzada, Federal University of Paraná), a centre of excellence for the study of Parkinson's disease in Brazil. Samples will be analysed by targeted liquid chromatography/mass spectrometry (LC/MS) metabolomics (Prof Skene (University of Surrey). Additional added value will be provided by employing a second metabolomics platform, untargeted 1H NMR metabolomics to characterise brain, plasma and urine metabolite changes in the rat model (Dr Swann, University of Reading). The application of two complementary analytical approaches ensures wide metabolome coverage and using multiple sample types allows the metabolic perturbations induced by sleep deprivation in PD to be studied at different levels. The planned combination of behavioural, neurochemical and metabolomic approaches will enable a multi-faceted observation of circulating and central neuronal parameters that could identify possible molecular biomarkers of early neurodegeneration in PD with potential diagnostic value. There will also be a mutual exchange of researchers and postgraduate students between the UK and Brazil to share new ideas, techniques and approaches allowing mutual (global) growth. The results of the proposed experiments will advance understanding of the mechanisms of PD and its inter-relationship with sleep/wake processing. Creation of a Brazil-United Kingdom research network will also provide a foundation for future studies and collaboration.