Heterogeneity of Microglia Phenotypes: Developmental, Functional and Some Therapeutic Considerations

Yun Yuan1, Chunyun Wu1, Eng-Ang Ling2

  • 1Department of Anatomy and Histology/Embryology, Kunming Medical University, 1168 West Chunrong Road, Kunming, China.

Abstract

Insights

Microglia, including amoeboid (AMCs) and ramified (RMCs) forms, shift to M1/M2 phenotypes during brain pathology. Targeting M2 polarization offers neuroprotection, while TSPO radioligands aid early brain lesion detection.

Area of Science:

  • Neuroscience
  • Immunology
  • Cell Biology

Background:

  • Microglia are crucial for brain homeostasis, transitioning from amoeboid microglial cells (AMCs) in development to ramified microglial cells (RMCs) in mature brains.
  • In neuropathological conditions, microglia activate into M1 and M2 phenotypes, with their roles being a significant area of research.

Purpose of the Study:

  • To review the developmental stages of AMCs and RMCs.
  • To discuss the functions of different microglial phenotypes (M1/M2) in neuropathological contexts.
  • To explore therapeutic strategies targeting microglial activation.

Main Methods:

  • Literature review focusing on microglial development, function, and phenotypes (M1/M2).
  • Analysis of experimental evidence regarding factors modulating microglial phenotype.
  • Examination of emerging diagnostic tools like TSPO radioligands.

Main Results:

  • Microglia perform functions such as phagocytosis, cytokine production, and synaptogenesis, but prolonged activation can be detrimental.
  • M1 and M2 phenotypes play distinct roles in various neuropathologies.
  • Microglial phenotype is influenced by stimuli, local environment, epigenetics, and compounds like herbal agents.

Conclusions:

  • M2 microglial polarization is generally considered neuroprotective.
  • Therapeutic strategies aimed at suppressing M1 activation, potentially using anti-inflammatory or herbal agents, may alleviate neuroinflammation.
  • 18 kDa translocator protein (TSPO) radioligands show promise for early detection of brain lesions via positron emission tomography.

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