Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Cell Communication / drug effects
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Cell Communication / immunology
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Cell Survival / drug effects
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Cell Survival / immunology
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Central Nervous System / drug effects
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Central Nervous System / immunology
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Central Nervous System / physiopathology*
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Chemotaxis / drug effects
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Chemotaxis / physiology
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Coculture Techniques
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Culture Media, Conditioned / pharmacology
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Interleukin-1 / metabolism
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Interleukin-1 / pharmacology
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Interleukin-6 / metabolism
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Interleukin-6 / pharmacology
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Mice
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Microglia / drug effects
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Microglia / immunology*
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Microglia / pathology
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Nerve Degeneration / chemically induced
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Nerve Degeneration / immunology
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Nerve Degeneration / physiopathology*
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Neuroblastoma
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Neurons / drug effects
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Neurons / immunology*
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Neurons / pathology
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Peptide Fragments / immunology
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Peptide Fragments / pharmacology
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Prion Diseases / chemically induced
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Prion Diseases / immunology
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Prion Diseases / physiopathology*
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Prions / immunology
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Prions / pharmacology*
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Reaction Time / drug effects
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Reaction Time / immunology
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Time Factors
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Tumor Cells, Cultured
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Tumor Necrosis Factor-alpha / metabolism
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Tumor Necrosis Factor-alpha / pharmacology
Substances
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Culture Media, Conditioned
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Interleukin-1
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Interleukin-6
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Peptide Fragments
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Prions
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Tumor Necrosis Factor-alpha