UCLA

Microglia are the resident immune cells of the central nervous system (CNS) and they carry out numerous and diverse functions throughout the lifespan. A central feature of microglia that allows them to carry out such diverse functional roles is phenotypic flexibility. Microglia can rapidly alter their morphology, secretion of signaling factors, and gene expression, in addition to remodeling other cellular attributes. The field has characterized a few microglial cell surface receptors that can instruct microglia about specific cell processes that are needed such as phagocytosis, synapse support, and disease associated response. However, much remains unknown about how microglia integrate information from numerous receptors and coordinately regulate multiple cell properties to rapidly shift into the appropriate cellular phenotype. Mitochondria, generally known for their ATP / energy producing capability, may play a critical role in this process of regulating cell properties and function. This dissertation aims to build on our current understanding of microglial function and how mitochondria may play critical roles in regulating microglial attributes in the CNS. In chapter 1, I will outline key microglia functions and supporting evidence that mitochondria can regulate cellular function. Chapter 2 will focus on how mitochondrial properties change and are linked to microglial morphology through the rodent lifespan and during inflammatory insults. Chapter 3 is dedicated to understanding mitochondrial roles during early development of the rodent brain and how mitochondrial morphology remodeling is linked to microglial phagocytic structures. Almost nothing is known about microglial mitochondria in vivo. Hence, the work outlined in this dissertation project provides foundational and essential information about microglial mitochondrial function. This will enable numerous future studies aiming to understand how microglial cellular response is shaped by mitochondrial state in the CNS.