Abstract
We recently established mouse microglial cells persistently infected with mouse-adapted scrapie ME7 (ScMG20/ME7) for in vitro study of prion pathogenesis. Here, we found that ScMG20/ME7 cells were hypersensitive to P2X7 receptor agonists, as demonstrated by sustained Ca(2+) influx, membrane pore formation, cell death, and interleukin-1beta release. P2X7 mRNA expression was upregulated in these cells, and also in scrapie-infected mice brains. Treatment with pentosan polysulfate eliminated the infectivity and disease-related forms of prion protein from ScMG20/ME7 cell cultures, however, hypersensitivity of P2X7 receptors remained. These results suggest that prion infections may strongly affect the P2X7 receptor system in mouse microglial cells.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adenosine Triphosphate / analogs & derivatives
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Adenosine Triphosphate / pharmacology*
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Animals
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Calcium Signaling / drug effects
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Cell Line
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Dose-Response Relationship, Drug
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Mice
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Mice, Inbred Strains
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Microglia / drug effects
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Microglia / pathology*
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Pentosan Sulfuric Polyester / pharmacology
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Prions / pathogenicity*
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Purinergic P2 Receptor Agonists*
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Receptors, Purinergic P2 / metabolism
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Receptors, Purinergic P2 / physiology
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Receptors, Purinergic P2X7
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Scrapie / pathology*
Substances
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P2rx7 protein, mouse
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Prions
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Purinergic P2 Receptor Agonists
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Receptors, Purinergic P2
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Receptors, Purinergic P2X7
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Pentosan Sulfuric Polyester
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3'-O-(4-benzoyl)benzoyladenosine 5'-triphosphate
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Adenosine Triphosphate