Heterogeneity of Microglia Phenotypes: Developmental, Functional and Some Therapeutic Considerations.
BACKGROUND
Microglia play a pivotal role in maintaining homeostasis in complex brain environment. They first exist as amoeboid microglial cells (AMCs) in the developing brain, but with brain maturation, they transform into ramified microglial cells (RMCs). In pathological conditions, microglia are activated and have been classified into M1 and M2 phenotypes. The roles of AMCs, RMCs and M1/M2 microglia phenotypes especially in pathological conditions have been the focus of many recent studies.


METHODS
Here, we review the early development of the AMCs and RMCs and discuss their specific functions with reference to their anatomic locations, immunochemical coding etc. M1 and M2 microglia phenotypes in different neuropathological conditions are also reviewed.


RESULTS
Activated microglia are engaged in phagocytosis, production of proinflammatory mediators, trophic factors and synaptogenesis etc. Prolonged microglia activation, however, can cause damage to neurons and oligodendrocytes. The M1 and M2 phenotypes featured prominently in pathological conditions are discussed in depth. Experimental evidence suggests that microglia phenotype is being modulated by multiple factors including external and internal stimuli, local demands, epigenetic regulation, and herbal compounds.


CONCLUSION
Prevailing views converge that M2 polarization is neuroprotective. Thus, proper therapeutic designs including the use of anti-inflammatory drugs, herbal agents may be beneficial in suppression of microglial activation, especially M1 phenotype, for amelioration of neuroinflammation in different neuropathological conditions. Finally, recent development of radioligands targeting 18 kDa translocator protein (TSPO) in activated microglia may hold great promises clinically for early detection of brain lesion with the positron emission tomography.
['Yuan|Yun|Y|', 'Wu|Chunyun|C|', 'Ling|Eng-Ang|EA|']
D001921:Brain D044127:Epigenesis, Genetic D006801:Humans D017628:Microglia D000066829:Neuroprotection D010641:Phenotype D028321:Plant Preparations D049268:Positron-Emission Tomography
Microglia phenotypes diverse immunochemical coding microglia
functions neurodegenerative diseases normal developing and mature brain phenotype modulation.