Lipid dynamics and metabolism in microglial function

小胶质细胞功能中的脂质动力学和代谢

• 批准号: RGPIN-2019-06062
• 负责人: Todd, Kathryn
• 金额: $ 2.33万
• 依托单位: University of Alberta
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2021
• 资助国家: 加拿大
• 起止时间: 2021-01-01 至 2022-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=738685
• 关键词: Lipid; dynamics; metabolism; microglial; function

Inflammation is normally an immune process intended to protect and repair tissue that has been damaged by infection or injury, however in the brain and spinal cord microglia are specialized immune cells that have adapted inflammatory mechanisms to carry our natural supportive roles. While we are continuing to gain new insights into how microglia carry out their normal functions, there are many questions that have yet to be answered. Two unique features that contribute to microglial function in the brain are: their dynamic behaviour - microglia are capable of changing shape, moving rapidly through brain tissue, and expanding their size to engulf other objects; and their ability to survive in diverse environments - during a stroke microglia survive and function in the absence of blood flow and nutrients while other cells die. In the current proposal we aim to investigate the means by which microglia are capable of such unique functions, focusing on the following specific questions. Question 1 - What mechanisms allow microglia to expand and contract the cell surface while moving through tissue, engulfing material, and undergoing shape transitions? Question 2 - How do microglia process and store lipid material ingested while clearing debris from brain tissue? Question 3 - Can inhibition of lipid storage alter microglial functions and modify natural inflammatory roles? These questions will allow us to address some of the fundamental functions that occur during inflammation of the brain and spinal cord, and in doing so allow us to better understand what causes inflammation to damage healthy tissue during disease or injury.

炎症通常是一种免疫过程，旨在保护和修复因感染或损伤而受损的组织，然而在大脑和脊髓中，小胶质细胞是一种特殊的免疫细胞，它适应了炎症机制，发挥了我们自然的支持作用。虽然我们对小胶质细胞如何执行其正常功能有了新的认识，但仍有许多问题尚未得到解答。大脑中促成小胶质细胞功能的两个独特特征是：它们的动态行为——小胶质细胞能够改变形状，在脑组织中快速移动，并扩大其大小以吞噬其他物体；它们在不同环境下的生存能力——在中风期间，小胶质细胞在缺乏血液流动和营养的情况下存活并发挥作用，而其他细胞则死亡。在目前的建议中，我们的目标是研究小胶质细胞能够发挥这种独特功能的手段，重点关注以下具体问题。问题1：什么机制允许小胶质细胞在穿过组织、吞噬物质和经历形状转变时扩张和收缩细胞表面？问题2：小胶质细胞在清除脑组织碎片的同时如何处理和储存摄入的脂质物质？问题3：抑制脂质储存能否改变小胶质细胞功能并改变自然炎症作用？这些问题将使我们能够解决大脑和脊髓炎症期间发生的一些基本功能，并使我们能够更好地理解是什么原因导致炎症在疾病或损伤期间损害健康组织。