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Specific microglial phagocytic phenotype and decrease of lipid oxidation in white matter areas during aging:

Paula Sanchez-Molina1, Beatriz Almolda1, Núria Benseny-Cases2

  • 1Institute of Neurosciences, Universitat Autònoma de Barcelona, Bellaterra, Barcelona, Spain; Department of Cell Biology, Physiology and Immunology, Universitat Autònoma de Barcelona, Bellaterra, Barcelona, Spain.

Neurobiology of Aging
|June 17, 2021
PubMed
Summary

Aging causes neuroinflammation, altering microglial cells in the brain. This study reveals how aging affects microglial cells in white matter, linking them to myelin damage and altered lipid oxidation.

Keywords:
AgingCytokinesLipid oxidationMicrogliaMyelinNeuroinflammationPhagocytosis

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Area of Science:

  • Neuroscience
  • Immunology
  • Cell Biology

Background:

  • Physiological aging involves an imbalance of inflammatory mediators, leading to neuroinflammation.
  • Microglial cells, the brain's immune cells, change with age and vary across brain regions.
  • Understanding these age-related microglial changes is crucial for brain health.

Purpose of the Study:

  • To investigate how aging influences microglial cells in different brain areas.
  • To examine the role of specific cytokines (IL-10 and IL-6) in age-related microglial function.
  • To explore the impact of aging on myelin integrity and lipid oxidation in white matter.

Main Methods:

  • Utilized transgenic mice overproducing anti-inflammatory IL-10 or pro-inflammatory IL-6.
  • Analyzed microglial cell phenotype and phagocytic activity in various brain regions.
  • Assessed myelin integrity and lipid oxidation levels in white matter areas.

Main Results:

  • Aging microglial cells in white matter show a phenotype associated with myelin recognition, suggesting myelin damage.
  • IL-10 overproduction accelerated and sustained this microglial phenotype, while IL-6 exacerbated it.
  • A novel finding of reduced lipid oxidation in aged white matter was observed, irrespective of cytokine levels.
  • Increased myelin engulfment by microglia was noted in aged transgenic mice.

Conclusions:

  • Aging induces specific changes in microglial cells within white matter, linked to myelin damage.
  • Cytokine balance (IL-10 vs. IL-6) modulates age-related microglial responses to myelin.
  • Reduced lipid oxidation in aging white matter is a significant, previously unrecognized phenomenon.
  • Further research into microglial regulation of myelin lipid oxidation during aging is warranted.