What are activated and reactive glia and what is their role in neurodegeneration?

Area of Science:

• Neuroscience
• Cell Biology
• Pathology

Background:

• Microglia and astrocytes, key non-neuronal cells in the CNS, exhibit significant changes in morphology, transcription, and function during injury and disease.
• These cellular alterations are implicated in the pathogenesis and dysfunction of the central nervous system (CNS).
• Microglia, the brain's resident macrophages, are termed "activated" when they modify inflammatory mediator production, surveillance behavior, and influence astrocyte function.

Purpose of the Study:

• To define the terms "activation" in microglia and "reactivity" in astrocytes.
• To elucidate the contribution of these altered glial states to neurodegenerative diseases (ND).
• To review the historical context, transcriptomic profiles, and mechanistic functions of these cells in ND.

Main Methods:

• Historical review of histopathological descriptions of microglia and astrocytes.
• Analysis of transcriptomic identities of activated and reactive glial cells.
• Survey of mechanistic understanding of glial cell functions in neurodegenerative disease.

Main Results:

• The study clarifies the evolving definitions and understanding of microglial activation and astrocyte reactivity.
• It highlights the dynamic changes in inflammatory mediator production and cellular surveillance by microglia.
• It details how reactive astrocytes alter homeostatic functions and can contribute to scar formation.

Conclusions:

• Understanding microglial activation and astrocyte reactivity is crucial for comprehending neurodegenerative disease progression.
• These cellular states, while complex, offer potential therapeutic targets within the CNS.
• Further mechanistic studies are needed to fully unravel the roles of these glial cells in health and disease.