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Microglia, the resident macrophages of the central nervous system (CNS), are important players in both physiological and pathological contexts. Highly phagocytic and motile cells, they are involved in a variety of biological processes, ranging from glio-, vasculo-, and neurogenesis to synaptic refinement and myelination. They critically contribute to proper brain development and brain homeostasis across the lifespan and are largely implicated in brain diseases. A growing body of evidence, based on recent Genome-wide Association Studies (GWAS), shows that multiple genetic variants associated with an increased risk of developing neurodegenerative disorders are highly enriched in microglia within the CNS, suggesting that microglial dysfunction underlies susceptibility to neurodegeneration. However, how and when these risk genes modulate microglial function and thus contribute to brain pathology remains not entirely clear. Here, the many roles of these cells in the healthy and diseased brain will be discussed, providing examples of how defective microglia can affect brain maturation and function, with long-lasting consequences on behavior. In addition, the relevance of critical windows during development will be highlighted, speculating on the link between microglial dysfunction in the early postnatal stages and increased vulnerability for developing neurodegeneration later in life.
