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Ex vivo cultures of microglia from young and aged rodent brain reveal age-related changes in microglial function.

Abstract
To understand how microglial cell function may change with aging, various protocols have been developed to isolate microglia from the young and aged central nervous system (CNS). Here we report modification of an existing protocol that is marked by less debris contamination and improved yields and demonstrate that microglial functions are varied and dependent on age. Specifically, we found that microglia from aged mice constitutively secrete greater amounts of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) relative to microglia from younger mice and are less responsive to stimulation. Also, microglia from aged mice have reduced glutathione levels and internalize less amyloid beta peptide (Aβ) while microglia from mice of all ages do not retain the amyloid beta peptide for a significant length of time. These studies offer further support for the idea that microglial cell function changes with aging. They suggest that microglial Aβ phagocytosis results in Aβ redistribution rather than biophysical degradation in vivo and thereby provide mechanistic insight to the lack of amyloid burden elimination by parenchymal microglia in aged adults and those suffering from Alzheimer's disease.
AuthorsEmalick G Njie, Ellen Boelen, Frank R Stassen, Harry W M Steinbusch, David R Borchelt, Wolfgang J Streit
JournalNeurobiology of aging (Neurobiol Aging) Vol. 33 Issue 1 Pg. 195.e1-12 (Jan 2012) ISSN: 1558-1497 [Electronic] United States
PMID20580465 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2012. Published by Elsevier Inc.
Chemical References
  • Amyloid beta-Peptides
  • Interleukin-6
  • Tumor Necrosis Factor-alpha
  • Glutathione
Topics
  • Aging (physiology)
  • Alzheimer Disease (etiology)
  • Amyloid beta-Peptides (metabolism)
  • Animals
  • Brain (cytology, physiology)
  • Cell Survival
  • Cells, Cultured
  • Glutathione (metabolism)
  • Interleukin-6 (metabolism)
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Microglia (metabolism, physiology)
  • Phagocytosis
  • Tumor Necrosis Factor-alpha (metabolism)

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