Phenotypic and functional changes in glial cells as a function of age

Neurobiol Aging. 2002 Jan-Feb;23(1):105-15. doi: 10.1016/s0197-4580(01)00258-5.


Both in vivo and in vitro investigations point to an important role for the immune system in the development of age-related neurodegeneration. Microglia isolated from aged female F344 rats, 18-20 months, show a higher percentage of cells with an ameboid morphology indicative of activation, whereas, astrocytes had a quiescent morphology. The ability of astrocytes and microglia to attenuate toxin-induced neuronal injury was examined. Post-natal day 1-3 pup cells optimally rescued neurons from Abeta-induced toxicity, whereas mixed glial cells from 18-20 month old rats were unable to rescue neurons from Abeta-induced toxicity. Our results suggested the appearance of a neurotoxic co-factor, therefore we investigated the basal level of nitric oxide and pro-inflammatory cytokines to determine if altered levels of immune mediators play a role in the toxicity. Mitogen-stimulated nitric oxide production increased 10 fold with age of donor, whereas, only the pup cells expressed an increase in TNF-alpha production. Basal levels of pro-inflammatory cytokines, as measured by RNA protection assays, increased with age. In particular, IL-1beta was increased 2 fold between adult and aged glial cells. The elevated cytokine expression may contribute to enhanced susceptibility to neurodegenerative diseases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / physiology*
  • Amyloid beta-Peptides / toxicity
  • Animals
  • Autoradiography
  • Cell Division / physiology
  • Cell Separation
  • Cells, Cultured
  • Cerebral Cortex / cytology
  • Coloring Agents
  • Cytokines / biosynthesis
  • Female
  • L-Lactate Dehydrogenase / metabolism
  • Neuroglia / metabolism
  • Neuroglia / physiology*
  • Neuroglia / ultrastructure
  • Neurons / drug effects
  • Neurons / metabolism
  • Nitric Oxide / biosynthesis
  • Nuclease Protection Assays
  • PC12 Cells
  • Phenotype
  • Rats
  • Rats, Inbred F344
  • Respiratory Burst / physiology
  • Tumor Necrosis Factor-alpha / metabolism


  • Amyloid beta-Peptides
  • Coloring Agents
  • Cytokines
  • Tumor Necrosis Factor-alpha
  • Nitric Oxide
  • L-Lactate Dehydrogenase