Microglia during development and aging

Pharmacol Ther. 2013 Sep;139(3):313-26. doi: 10.1016/j.pharmthera.2013.04.013. Epub 2013 Apr 30.


Microglia are critical nervous system-specific cells influencing brain development, maintenance of the neural environment, response to injury, and repair. They contribute to neuronal proliferation and differentiation, pruning of dying neurons, synaptic remodeling and clearance of debris and aberrant proteins. Colonization of the brain occurs during gestation with an expansion following birth with localization stimulated by programmed neuronal death, synaptic pruning, and axonal degeneration. Changes in microglia phenotype relate to cellular processes including specific neurotransmitter, pattern recognition, or immune-related receptor activation. Upon activation, microglia cells have the capacity to release a number of substances, e.g., cytokines, chemokines, nitric oxide, and reactive oxygen species, which could be detrimental or beneficial to the surrounding cells. With aging, microglia shift their morphology and may display diminished capacity for normal functions related to migration, clearance, and the ability to shift from a pro-inflammatory to an anti-inflammatory state to regulate injury and repair. This shift in microglia potentially contributes to increased susceptibility and neurodegeneration as a function of age. In the current review, information is provided on the colonization of the brain by microglia, the expression of various pattern recognition receptors to regulate migration and phagocytosis, and the shift in related functions that occur in normal aging.

Keywords: AD; ATP; Aging; Alzheimer's disease; Aβ; BBB; C1q; CD; CNS; CR3; CX3CL1; CX3CR1; Cl(−); Development; GD; IFN; IL; K(+); LPS; MAPK; MHC; Microglia; NO; P2; P2X receptors; PI3K; PND; PRR; Synapse stripping; TGFβ; TLR; TNF; TREM-2; adenosine triphosphate; amyloid beta; blood brain barrier; central nervous system; chloride; cluster of differentiation; complement 1q; complement receptor 3; fractalkine or neurotactin; fractalkine receptor; gestational day; interferon; interleukin; lipopolysaccharide; major histocompatibility complex; mitogen-activated protein kinase; nitric oxide; pattern recognition receptors; phosphoinositide 3-kinase; postnatal day; potassium; purinergic receptors; toll-like receptors; transforming growth factor beta; triggering receptor expressed on myeloid cells-2; tumor necrosis factor.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Aging / physiology*
  • Animals
  • Brain / growth & development
  • Brain / physiology*
  • Cell Differentiation / physiology
  • Cell Movement / physiology
  • Cell Proliferation
  • Humans
  • Microglia / metabolism*
  • Nerve Degeneration / metabolism
  • Neurons / physiology
  • Phagocytosis / physiology