Microglial physiology: unique stimuli, specialized responses

Richard M Ransohoff1, V Hugh Perry

  • 1Neuroinflammation Research Center, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio 44195, USA. ransohr@ccf.org

Insights

Microglia, the brain's immune cells, constantly survey their environment. Their diverse functions and activation states in neurological diseases offer potential therapeutic targets.

Area of Science:

  • Neuroscience
  • Immunology
  • Cell Biology

Background:

  • Microglia are the central nervous system's resident macrophages.
  • In a healthy brain, their phenotype is influenced by neural and glial cells and the blood-brain barrier.
  • Microglia are constantly active, surveying their microenvironment.

Purpose of the Study:

  • To describe the dynamic nature and diverse functions of microglia.
  • To emphasize the need for qualifying the term "activated microglia" based on disease-specific states.
  • To highlight the therapeutic potential of manipulating microglial functions in neurological diseases.

Main Methods:

  • Review of existing literature on microglia biology and function.
  • Analysis of microglial responses to disturbances in nervous system homeostasis.
  • Examination of diverse effector functions in various disease contexts.

Main Results:

  • Microglia exhibit a distinct phenotype in the healthy brain, maintained by local factors and the blood-brain barrier.
  • Microglia rapidly alter their phenotype (morphology, antigen expression) in response to homeostatic disturbances, termed "activation".
  • Microglia possess diverse effector functions, similar to macrophages in other organs, which vary significantly across different disease states.

Conclusions:

  • The term "activated microglia" requires precise qualification to reflect distinct, disease-specific functional states.
  • Understanding the diverse effector functions of microglia is crucial for developing targeted therapies.
  • Modulating microglial effector functions holds significant potential for treating a wide range of neurological diseases.