Temporal and spatial relationship between the death of PrP-damaged neurones and microglial activation.
Previous studies have demonstrated a role for microglia in the neuronal loss that occurs in the transmissible spongiform encephalopathies or prion diseases. In the present studies, the processes that lead to the death of neurones treated with synthetic peptides derived from the prion protein (PrP) were fully activated within 1 h, although neuronal cell death was not seen until 24 h later. Similarly, neurones exposed to PrP peptides for only 1 h activated microglia and a temporal relationship between the production of interleukin-6, an indicator of microglial activation, and microglial killing of PrP-treated neurones was also demonstrated. Activation of microglia and microglia-mediated killing of PrP-treated neurones or scrapie-infected neuroblastoma cells were maximal only when microglia were in direct contact with neurones.
D000818:Animals; D002450:Cell Communication / Q000187:drug effects / Q000276:immunology; D002470:Cell Survival / Q000187:drug effects / Q000276:immunology; D002490:Central Nervous System / Q000187:drug effects / Q000276:immunology / Q000503:physiopathology*; D002633:Chemotaxis / Q000187:drug effects / Q000502:physiology; D018920:Coculture Techniques; D017077:Culture Media, Conditioned / Q000494:pharmacology; D007375:Interleukin-1 / Q000378:metabolism / Q000494:pharmacology; D015850:Interleukin-6 / Q000378:metabolism / Q000494:pharmacology; D051379:Mice; D017628:Microglia / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D009410:Nerve Degeneration / Q000139:chemically induced / Q000276:immunology / Q000503:physiopathology*; D009447:Neuroblastoma; D009474:Neurons / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D010446:Peptide Fragments / Q000276:immunology / Q000494:pharmacology; D017096:Prion Diseases / Q000139:chemically induced / Q000276:immunology / Q000503:physiopathology*; D011328:Prions / Q000276:immunology / Q000494:pharmacology*; D011930:Reaction Time / Q000187:drug effects / Q000276:immunology; D013997:Time Factors; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism / Q000494:pharmacology
D017077:Culture Media, Conditioned; D007375:Interleukin-1; D015850:Interleukin-6; D010446:Peptide Fragments; D011328:Prions; D014409:Tumor Necrosis Factor-alpha