The Role of Brain Lymphatic Endothelial Cells (BLECs) in Behaviors Relevant to Neurodegenerative Disease.

脑淋巴内皮细胞 (BLEC) 在神经退行性疾病相关行为中的作用。

• 批准号: 2250117
• 金额: --
• 依托单位: University College London
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2019
• 资助国家: 英国
• 起止时间: 2019 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2250117
• 关键词: Role; Brain; Lymphatic; Endothelial; Cells

This project will aim to explore the role of Brain Lymphatic Endothelial Cells (BLECs) in neurodegenerative disease. Using Zebrafish as the model organism, I will elucidate the function of this novel cell type both in healthy and pathological contexts. Using genetic, chemogenetic, optogenetic and pharmacological manipulations, I will investigate how BLECs respond to perturbations of brain function. As an optically transparent organism, the zebrafish allows for high throughput imaging of BLECs using confocal, 2-photon and super-resolution microscopy after normal and pathological brain activity. I will also assess whether BLECs have a role in shaping behaviors such as sleep by perturbing BLECs and observing changes in behaviour. Since sleep has been linked to metabolic brain clearance, elucidating a role of BLECs in sleep may be of particular relevance to their potential role in neurodegenerative processes. Overall, molecular, cellular and behavioral characterizations of this brain lymphatic cell type may uncover novel pathological mechanisms underlying neurodegeneration as well as lead to the identification of new therapeutic targets.

该项目旨在探索脑淋巴管内皮细胞（BLECs）在神经退行性疾病中的作用。使用斑马鱼作为模式生物，我将阐明这种新的细胞类型在健康和病理环境中的功能。使用遗传学，化学遗传学，光遗传学和药理学操作，我将研究如何BLECs响应脑功能的扰动。作为一种光学透明的生物体，斑马鱼允许在正常和病理性脑活动后使用共焦、双光子和超分辨率显微镜对BLECs进行高通量成像。我还将通过扰乱BLECs和观察行为变化来评估BLECs是否在塑造行为（如睡眠）方面发挥作用。由于睡眠与代谢性脑清除有关，因此阐明BLEC在睡眠中的作用可能与其在神经退行性过程中的潜在作用特别相关。总体而言，这种脑淋巴细胞类型的分子，细胞和行为特征可能揭示神经变性的新病理机制，并导致新的治疗靶点的识别。