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Life and Death of Microglia

Abstract

The importance of microglial cells in the maintenance of a well-functioning central nervous system (CNS) cannot be overstated. As descendants of the myelomonocytic lineage they are industrious housekeepers and watchful sentries that safeguard a homeostatic environment through a number of mechanisms designed to provide protection of fastidious neurons at all times. Microglia become particularly active after homeostasis has been perturbed by physical injury or other insults and they enter into a state of activation which is determined largely by the nature and severity of the lesion. Microglial activation is the main cellular event in acute neuroinflammation and essential for wound healing in the CNS. Recent studies from this laboratory have been focused on microglia in the aging brain and identified structural abnormalities, termed microglial dystrophy, that are consistent with cell senescence and progress to a form of accidental cell death that is marked by cytoplasmic degeneration and has been termed cytorrhexis. Cytorrhexis of microglia is infrequent in the normally aged human brain and non-detectable in aged rodents, but its occurrence increases dramatically during neurodegenerative conditions, including Alzheimer’s disease (AD) in humans and motoneuron disease in transgenic rats. The identification of degenerating microglia has given rise to a novel theory of AD pathogenesis, the microglial dysfunction hypothesis, which views the loss of microglial neuroprotection as a central event in neurodegenerative disease development.

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Correspondence to Wolfgang J. Streit.

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Supported by: National Institutes of Health Grant AG023665.

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Streit, W.J., Xue, QS. Life and Death of Microglia. J Neuroimmune Pharmacol 4, 371 (2009). https://doi.org/10.1007/s11481-009-9163-5

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Keywords

  • ontogeny
  • neuroinflammation
  • cell senescence
  • microglial dystrophy
  • neuroprotection