Microglia in Health and Disease

Abstract

Microglia, the major myeloid cells of the central nervous system (CNS) are implicated in physiologic processes and in the pathogenesis of several CNS disorders. Since their initial description early in the 20th century, our ability to identify and isolate microglia has significantly improved and new research is providing insight into the functions of these cells in sickness and in health. Here, we review recent advances in our understanding of the role of microglia in physiological and pathological processes of the CNS with a focus on multiple sclerosis and Alzheimer's disease. Because of the prominent roles CX3CR1 and its ligand fractalkine played in bringing about these advances, we discuss the physiological and pathological roles of microglia as viewed from the CX3CR1-fractalkine perspective, providing a unique viewpoint. Based on the most recent studies of molecular profiling of microglia, we also propose a molecular and functional definition of microglia that incorporates the properties attributed to these cells in recent years.

Figure 1.

Microglia begin to clear myelin debris at EAE onset. Three-dimensional reconstructions from serial block face scanning EM of spinal cord tissues of a mouse at day of EAE onset show a large flap of myelin debris (blue) engaged by a microglial process (green). A nearby monocyte (red cytosol; golden nucleus) enwraps a myelin internode and is actively removing myelin. Both monocyte and microglial cell (with yellow nucleus) contain myelin inclusions (blue), although those of the monocyte are larger and more numerous.

Figure 2.

β-Amyloid (Aβ) deposits are surrounded by microglia. Microglia, stained here in brown for CD11b, cluster around sites of Aβ deposition, stained in green with thioflavin S, in a mouse model of cerebral amyloid deposition.