NR AXPA
AU Iwamaru,Y.; Takenouchi,T.; Imamura,M.; Sato,M.; Okada,H.; Masujin,K.; Yokoyama,T.; Mohri,S.; Kitani,H.
TI Prion Infection Correlates with Hypersensitivity of P2X7 Nucleotide Receptor in Mouse Microglial Cells
QU International Conference - Prion 2007 (26.-28.9.2007) Edinburgh International Conference Centre, Edinburgh, Scotland, UK - Book of Abstracts: Pathology and Pathogenesis P03.55
IA http://www.prion2007.com/pdf/Prion Book of Abstracts.pdf
PT Konferenz-Poster
AB
The pathological features of prion diseases are brain vacuolation, neuronal death, astrocytosis and microgliosis. The microglial activation follows PrPsc accumulation and precedes neuronal cell loss in various rodent models of prion diseases. Activated microglia were found to colocalize with the spongiform change in the brain tissues of prion-infected animals, suggesting that these cells play an important role in the pathogenesis of prion diseases. The P2X7 receptor (P2X7R) is one of the major ATPgated ion channels expressed in microglia, and transduces ATP-mediated signals to these cells to respond to physiological and pathological changes in the brain. ATP interacts with P2X7R and induces several cellular responses:
Ca2+ influx, formation of large non-selective membrane pores, induction of microglial cell death, and release of mature interleukin-1ß (IL-1ß). The expression of P2X7R in microglia is upregulated in the rodent models of several neurodegenerative diseases, such as Alzheimer's disease, indicating the possibility that the activation of P2X7R in microglia correlates with neuropathogenic processes in the brain. Recently, we have established mouse microglial cells persistently infected with various mouse-adapted prion strains. In this study, as an attempt to characterize cellular alterations in prioninfected microglial cells, we investigated P2X7R functions in these cells. Scrapieinfected microglial cells showed hypersensitivity of P2X7R, as demonstrated by an increase in the intracellular Ca2+ concentration, the formation of pores in the cell membrane, the induction of microglial cell death, and the release of mature IL-1ß. Furthermore, we demonstrated upregulation of P2X7R mRNA in the brains of scrapieinfected mice. These results suggest that prion infection correlates with hypersensitivity of P2X7R in microglial cells.
AD Y. Iwamaru, M. Imamura, H. Okada, K. Masujin, T. Yokoyama, S. Mohri, National Institute of Animal Health, Japan; T. Takenouchi, M. Sato, H. Kitani, National Institute of Agrobiological Sciences, Japan
SP englisch
PO Schottland
EA pdf-Datei und Poster (Autorenliste um H. Okada reduziert)