The metabolic journey of microglia from early development to adulthood

Microglia, the resident immune cells of the central nervous system (CNS), are vital for maintaining brain homeostasis during health and brain injury. Microglia exhibit diverse morphological adaptations across different brain regions and environmental cues, reflecting functional heterogeneity and regional differences. Although they comprise a smaller fraction of the total brain cells, microglia play critical roles in early brain development, which ranges from pruning weaker synapses to guiding neuronal responses, underscoring their importance in the formation of neural network as well as in the maintenance of CNS health. As bonafide brain-resident immune cells, they also partake in strong immune responses. We now recognize that different functional aspects of microglia are closely tied to changes in their metabolic requirements, which vary across different stages of development. However, a comprehensive coverage of microglial metabolism in light of its different roles in brain development remains limited. By examining the origins, colonization, and molecular signaling involved in early microgliogenesis and during adulthood, this review aims to highlight the significance of microglia metabolism in brain development. Additionally, the study investigates how metabolic changes during postnatal stages influence microglial activity, such as phagocytosis and neural sculpting, to maintain homeostasis. Exploring the metabolic profiles of microglia across their lifespan not only advances our understanding of brain homeostasis but also opens avenues for identifying metabolic pathways as potential therapeutic targets in neurodevelopmental and neurodegenerative diseases. This review contributes to the growing body of knowledge on microglial biology, emphasizing the need for further research into their metabolic regulation and its implications for CNS health.