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

本项目旨在探讨脑淋巴内皮细胞（BLECs）在神经退行性疾病中的作用。使用斑马鱼作为模式生物，我将阐明这种新型细胞类型在健康和病理背景下的功能。使用遗传学、化学遗传学、光遗传学和药理学操作，我将研究BLECs如何对脑功能的扰动作出反应。作为一种光学透明的生物，斑马鱼允许在正常和病理脑活动后使用共聚焦，双光子和超分辨率显微镜对BLECs进行高通量成像。我还将通过干扰blec和观察行为变化来评估blec是否在塑造行为（如睡眠）方面发挥作用。由于睡眠与代谢脑清除有关，阐明blc在睡眠中的作用可能与它们在神经退行性过程中的潜在作用特别相关。总的来说，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确定。

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.