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Microglia during development and aging
Authors:G Jean Harry
Institution:National Toxicology Program Laboratory, National Institute of Environmental Health Sciences, MD C1-04, 111 T.W. Alexander Drive, Research Triangle Park, NC 27709, United States
Abstract: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:ATP  adenosine triphosphate  AD  Alzheimer's disease    amyloid beta  BBB  blood brain barrier  Cl&minus    chloride  CD  cluster of differentiation  CR3  complement receptor 3  C1q  complement 1q  CNS  central nervous system  CX3CL1  fractalkine or neurotactin  CX3CR1  fractalkine receptor  GD  gestational day  IFN  interferon  MHC  major histocompatibility complex  MAPK  mitogen-activated protein kinase  PND  postnatal day  IL  interleukin  LPS  lipopolysaccharide  NO  nitric oxide  PRR  pattern recognition receptors  PI3K  phosphoinositide 3-kinase  K+  potassium  P2  purinergic receptors  TREM-2  triggering receptor expressed on myeloid cells-2  TLR  toll-like receptors  TGFβ  transforming growth factor beta  TNF  tumor necrosis factor
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