Phenotypic and functional changes in glial cells as a function of age.
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.
Yu
Wai H
WH
Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, ON, Canada.
Go
Lynle
L
Guinn
Barbara A
BA
Fraser
Paul E
PE
Westaway
David
D
McLaurin
JoAnne
J
D000375:Aging / Q000502:physiology*; D016229:Amyloid beta-Peptides / Q000633:toxicity; D000818:Animals; D001345:Autoradiography; D002455:Cell Division / Q000502:physiology; D002469:Cell Separation; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D004396:Coloring Agents; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D009457:Neuroglia / Q000378:metabolism / Q000502:physiology* / Q000648:ultrastructure; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis; D023282:Nuclease Protection Assays; D016716:PC12 Cells; D010641:Phenotype; D051381:Rats; D011916:Rats, Inbred F344; D016897:Respiratory Burst / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D016229:Amyloid beta-Peptides; D004396:Coloring Agents; D016207:Cytokines; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D007770:L-Lactate Dehydrogenase