Brain Parenchymal and Extraparenchymal Macrophages in Development, Homeostasis, and Disease

Area of Science:

• Neuroscience
• Immunology
• Cell Biology

Background:

• Microglia are the primary resident immune cells within the central nervous system (CNS), acting as professional phagocytes essential for brain homeostasis.
• These cells originate from primitive hematopoiesis in the yolk sac and migrate to the developing brain early in embryogenesis.
• Unlike other tissue macrophages, microglia self-renew within the CNS and do not typically derive from blood monocytes under normal conditions.

Purpose of the Study:

• To review recent advancements in understanding the origins, phenotypes, and functions of parenchymal microglia.
• To delineate the characteristics and origins of extraparenchymal macrophages residing in brain-border regions.
• To provide a comprehensive overview of microglial and extraparenchymal macrophage roles in both healthy and diseased CNS environments.

Main Methods:

• This review synthesizes findings from recent transcriptomic (RNA-sequencing) studies.
• It integrates data from developmental biology, immunology, and neuroscience research.
• Comparative analysis of microglial and extraparenchymal macrophage populations is discussed.

Main Results:

• Homeostatic microglia possess a distinct molecular signature, crucial for maintaining brain physiology.
• During pathological conditions, microglia exhibit significant phenotypic plasticity, adapting specialized functions to the disease context.
• Extraparenchymal macrophages in brain-border regions represent distinct populations with unique origins and characteristics.

Conclusions:

• A deeper understanding of microglial and extraparenchymal macrophage biology is emerging.
• Recognizing the distinct roles and plasticity of these cell types is vital for comprehending CNS health and disease.
• Future research directions may focus on targeting these cells for therapeutic interventions in neurological disorders.