Biomarkers of inflammation across the lung to brain axis as mediators of the adverse impacts of air pollution on brain health

肺到脑轴炎症的生物标志物作为空气污染对大脑健康不利影响的介质

基本信息

批准号：
2899572
负责人：
金额：
--
依托单位：
Imperial College London
依托单位国家：
英国
项目类别：
Studentship
财政年份：
2023
资助国家：
英国
起止时间：
2023 至无数据
项目状态：
未结题

来源：
https://gtr.ukri.org/projects?ref=studentship-2899572
关键词：
Biomarkers inflammation across lung brain

项目摘要

Recent epidemiological evidence has demonstrated neurological impacts of air pollution exposure across the life course, from early cognitive deficits in childhood, to poor mental health across adolescence to adulthood and increased dementia risk in old age. In this proposal we will investigate whether the adverse effects of air pollution are mediated via a lung to brain axis. We propose that pulmonary inflammation following inhalation of pollutant aerosols drives systemic responses that are translated to the brain across the blood brain barrier. This PhD aligns with the UKRI funded 'Hazard Identification Platform to Assess the Health Impacts from Indoor and Outdoor Air Pollutant Exposures, through Mechanistic Toxicology' project, in which aged individuals will be exposed to different source specific pollutant aerosols: diesel exhaust, woodsmoke and semi organic aerosol and cooking aerosols. Blood and nasal lavage samples from these individuals will be analysed for both established markers of systemic and neuroinflammation. In addition samples will be used to investigate novel biomarkers of exposure and response using LC-MS/NMR metabolomic approaches and analysis of circulating microRNA. This project will be delivered under the MRC Centre for Environment and Health, Molecular Signatures and Disease Pathways theme, building on the previous EU funded Exposomics project. It is envisaged that the project will have an equal split between lab-based analysis and bioinformatics/advanced statistical analysis.

最近的流行病学证据表明，从童年的早期认知缺陷到整个青春期的精神健康到成年期的不良心理健康以及老年痴呆症风险增加，整个生命过程中空气污染暴露的神经系统影响。在此提案中，我们将研究空气污染的不利影响是否是通过肺部到脑轴介导的。我们提出，吸入污染物气溶胶后肺部炎症驱动全身反应，这些反应在整个血脑屏障上转化为大脑。该博士通过机械毒理学的项目与UKRI资助的危险识别平台保持一致，以评估室内和室外空气污染物暴露的健康影响，在该项目中，年龄的个体将暴露于不同来源的特定来源污染物的气雾剂：柴油机和柴油机，柴油和半有机有机溶剂和烹饪机动体。这些个体的血液和鼻腔灌洗样本将分析已建立的系统性和神经炎症的标志。另外，样品将使用LC-MS/NMR代谢组方法和循环microRNA分析来研究暴露和反应的新型生物标志物。该项目将在MRC环境与健康中心，分子签名和疾病途径主题下交付，这是在先前的欧盟资助的外汇项目基础上建立的。可以预见，该项目将在基于实验室的分析和生物信息学/高级统计分析之间具有平等的分歧。