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

• 批准号: 2899572
• 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

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，空气污染暴露会对整个生命过程中的神经系统产生影响，从童年早期的认知缺陷，到青春期到成年期的心理健康状况不佳，以及老年痴呆症风险增加。在这项提案中，我们将研究空气污染的不利影响是否是通过肺到脑轴介导的。我们认为，吸入污染物气溶胶后的肺部炎症会驱动全身反应，并穿过血脑屏障转化到大脑。该博士学位与 UKRI 资助的“通过机械毒理学评估室内和室外空气污染物暴露对健康影响的危害识别平台”项目相一致，在该项目中，老年人将暴露于不同来源的特定污染物气溶胶：柴油机尾气、木烟和半固态污染物。有机气溶胶和烹饪气溶胶。将分析这些个体的血液和鼻腔灌洗样本中已确定的全身和神经炎症标志物。此外，样品将用于使用 LC-MS/NMR 代谢组学方法和循环 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、分子特征和疾病途径主题下实施，以之前欧盟资助的暴露组学项目为基础。预计该项目将在基于实验室的分析和生物信息学/高级统计分析之间平等分配。