Lipid dynamics and metabolism in microglial function

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，小胶质细胞是专门的免疫细胞，它们适应了炎症机制，以发挥我们的天然支持作用。虽然我们正在继续获得关于小胶质细胞如何执行其正常功能的新见解，但仍有许多问题尚未得到解答。两个独特的功能，有助于小胶质细胞在大脑中的功能是：他们的动态行为-小胶质细胞能够改变形状，快速移动通过脑组织，并扩大其大小吞噬其他物体;和他们的生存能力，在不同的环境中-在中风期间，小胶质细胞生存和功能在没有血流和营养的情况下，而其他细胞死亡。在目前的提案中，我们的目标是研究小胶质细胞能够实现这种独特功能的方法，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 -小胶质细胞如何处理和储存摄入的脂质物质，同时清除脑组织中的碎片？问题3：抑制脂质储存是否可以改变小胶质细胞的功能并改变天然炎症作用？这些问题将使我们能够解决大脑和脊髓炎症过程中发生的一些基本功能，这样做可以让我们更好地了解是什么导致炎症在疾病或损伤期间损害健康组织。

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.