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Distribution of the cellular prion protein (PrPC) in brains of livestock and domesticated species

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Abstract

In transmissible spongiform encephalopathies (TSEs) the prion protein (PrP) plays a central role in pathogenesis. The PrP gene (Prnp) has been described in a number of mammalian and avian species and its expression product, the cellular prion protein (PrPC), has been mapped in brains of different laboratory animals (rodent and non-human primates). However, mapping of PrPC expression in mammalian species suffering from natural (bovine and ovine) and experimental (swine) TSE or in species in which prion disease has never been reported (equine and canine) deserves further attention. Thus, localising the cellular prion protein (PrPC) distribution in brain may be noteworthy for the understanding of prion disease pathogenesis since lesions seem to be restricted to particular brain areas. In the present work, we analysed the distribution of PrPC expression among several brain structures of the above species. Our results suggest that the expression of PrPC, within the same species, differs depending on the brain structure studied, but no essential differences between the PrPC distribution patterns among the studied species could be established. Positive immunoreaction was found mainly in the neuropil and to a lesser extent in neuronal bodies which occasionally appeared strongly stained in discrete regions. Overall, the expression of PrPC in the brain was significantly higher in grey matter areas than in white matter, where accumulation of PrPSc is first observed in prion diseases. Therefore, other factors besides the level of expression of cellular PrP may account for the pathogenesis of TSEs

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References

  1. Bendheim PE, Brown HR, Rudelli RD, Scala LJ, Goller NL, Wen GY, Kascsak RJ, Cashman NR, Bolton DC (1992) Nearly ubiquitous tissue distribution of the scrapie agent precursor protein. Neurology 42:149–156

    Article  PubMed  CAS  Google Scholar 

  2. Borchelt DR, Koliatsos VE, Guarnieri M, Pardo CA, Sisodia SS, Price DL (1994) Rapid anterograde axonal transport of the cellular prion glycoprotein in the peripheral and central nervous systems. J Biol Chem 269:14711–14714

    PubMed  CAS  Google Scholar 

  3. Brown DR, Sassoon J (2002) Copper-dependent functions for the prion protein. Mol Biotechnol 22:165–178

    Article  PubMed  CAS  Google Scholar 

  4. Brown DR, Schulz-Schaeffer WJ, Schmidt B, Kretzschmar HA (1997) Prion protein-deficient cells show altered response to oxidative stress due to decreased SOD-1 activity. Exp Neurol 146:104–112

    Article  PubMed  CAS  Google Scholar 

  5. Bueler H, Aguzzi A, Sailer A, Greiner RA, Autenried P, Aguet M, Weissmann C (1993) Mice devoid of PrP are resistant to scrapie. Cell 73:1339–1347

    Article  PubMed  CAS  Google Scholar 

  6. Chen SG, Teplow DB, Parchi P, Teller JK, Gambetti P, Autilio-Gambetti L (1995) Truncated forms of the human prion protein in normal brain and in prion diseases. J Biol Chem 270:19173–19180

    Article  PubMed  CAS  Google Scholar 

  7. Colling SB, Collinge J, Jefferys JG (1996) Hippocampal slices from prion protein null mice: disrupted Ca (2+)-activated K+ currents. Neurosci Lett 209:49–52

    Article  PubMed  CAS  Google Scholar 

  8. Ford MJ, Burton LJ, Morris RJ, Hall SM (2002) Selective expression of prion protein in peripheral tissues of the adult mouse. Neuroscience 113:177–192

    Article  PubMed  CAS  Google Scholar 

  9. Gauczynski S, Peyrin JM, Haik S, Leucht C, Hundt C, Rieger R, Krasemann S, Deslys JP, Dormont D, Lasmezas CI, Weiss S (2001) The 37-kDa/67-kDa laminin receptor acts as the cell-surface receptor for the cellular prion protein. Embo J 20:5863–5875

    Article  PubMed  CAS  Google Scholar 

  10. Herms JW, Korte S, Gall S, Schneider I, Dunker S, Kretzschmar HA (2000) Altered intracellular calcium homeostasis in cerebellar granule cells of prion protein-deficient mice. J Neurochem 75:1487–1492

    Article  PubMed  CAS  Google Scholar 

  11. Jeffrey M, Martin S, Gonzalez L, Foster J, Langeveld JP, van Zijderveld FG, Grassi J, Hunter N (2006) Immunohistochemical features of PrP(d) accumulation in natural and experimental goat transmissible spongiform encephalopathies. J Comp Pathol 134:171–181

    Article  PubMed  CAS  Google Scholar 

  12. Jimenez-Huete A, Lievens PM, Vidal R, Piccardo P, Ghetti B, Tagliavini F, Frangione B, Prelli F (1998) Endogenous proteolytic cleavage of normal and disease-associated isoforms of the human prion protein in neural and non-neural tissues. Am J Pathol 153:1561–1572

    PubMed  CAS  Google Scholar 

  13. Kretzschmar HA, Stowring LE, Westaway D, Stubblebine WH, Prusiner SB, Dearmond SJ (1986) Molecular cloning of a human prion protein cDNA. DNA 5:315–324

    PubMed  CAS  Google Scholar 

  14. Laine J, Marc ME, Sy MS, Axelrad H (2001) Cellular and subcellular morphological localization of normal prion protein in rodent cerebellum. Eur J Neurosci 14:47–56

    Article  PubMed  CAS  Google Scholar 

  15. Liu T, Zwingman T, Li R, Pan T, Wong BS, Petersen RB, Gambetti P, Herrup K, Sy MS (2001) Differential expression of cellular prion protein in mouse brain as detected with multiple anti-PrP monoclonal antibodies. Brain Res 896:118–129

    Article  PubMed  CAS  Google Scholar 

  16. Mallucci GR, Ratte S, Asante EA, Linehan J, Gowland I, Jefferys JG, Collinge J (2002) Post-natal knockout of prion protein alters hippocampal CA1 properties, but does not result in neurodegeneration. Embo J 21:202–210

    Article  PubMed  CAS  Google Scholar 

  17. Mironov A Jr, Latawiec D, Wille H, Bouzamondo-Bernstein E, Legname G, Williamson RA, Burton D, DeArmond SJ, Prusiner SB, Peters PJ (2003) Cytosolic prion protein in neurons. J Neurosci 23:7183–7193

    PubMed  CAS  Google Scholar 

  18. Moser M, Colello RJ, Pott U, Oesch B (1995) Developmental expression of the prion protein gene in glial cells. Neuron 14:509–517

    Article  PubMed  CAS  Google Scholar 

  19. Moya KL, Sales N, Hassig R, Creminon C, Grassi J, Di Giamberardino L (2000) Immunolocalization of the cellular prion protein in normal brain. Microsc Res Tech 50:58–65

    Article  PubMed  CAS  Google Scholar 

  20. Peters PJ, Mironov A Jr, Peretz D, van Donselaar E, Leclerc E, Erpel S, DeArmond SJ, Burton DR, Williamson RA, Vey M, Prusiner SB (2003) Trafficking of prion proteins through a caveolae-mediated endosomal pathway. J Cell Biol 162:703–717

    Article  PubMed  CAS  Google Scholar 

  21. Prusiner SB (1996) Molecular biology and pathogenesis of prion diseases. Trends Biochem Sci 21:482–487

    Article  PubMed  CAS  Google Scholar 

  22. Prusiner SB (1982) Novel proteinaceous infectious particles cause scrapie. Science 216:136–144

    Article  PubMed  CAS  Google Scholar 

  23. Ryder SJ, Hawkins SA, Dawson M, Wells GA (2000) The neuropathology of experimental bovine spongiform encephalopathy in the pig. J Comp Pathol 122:131–143

    Article  PubMed  CAS  Google Scholar 

  24. Sales N, Rodolfo K, Hassig R, Faucheux B, Di Giamberardino L, Moya KL (1998) Cellular prion protein localization in rodent and primate brain. Eur J Neurosci 10:2464–2471

    Article  PubMed  CAS  Google Scholar 

  25. Stahl N, Borchelt DR, Hsiao K, Prusiner SB (1987) Scrapie prion protein contains a phosphatidylinositol glycolipid. Cell 51:229–240

    Article  PubMed  CAS  Google Scholar 

  26. Steele AD, Emsley JG, Ozdinler PH, Lindquist S, Macklis JD (2006) Prion protein (PrPC) positively regulates neural precursor proliferation during developmental and adult mammalian neurogenesis. Proc Natl Acad Sci USA 103:3416–3421

    Article  PubMed  CAS  Google Scholar 

  27. Taraboulos A, Jendroska K, Serban D, Yang SL, DeArmond SJ, Prusiner SB (1992) Regional mapping of prion proteins in brain. Proc Natl Acad Sci USA 89:7620–7624

    Article  PubMed  CAS  Google Scholar 

  28. Thuring CM, Erkens JH, Jacobs JG, Bossers A, Van Keulen LJ, Garssen GJ, Van Zijderveld FG, Ryder SJ, Groschup MH, Sweeney T, Langeveld JP (2004) Discrimination between scrapie and bovine spongiform encephalopathy in sheep by molecular size, immunoreactivity, and glycoprofile of prion protein. J Clin Microbiol 42:972–980

    Article  PubMed  CAS  Google Scholar 

  29. Van Rheede T, Smolenaars MM, Madsen O, De Jong WW (2003) Molecular evolution of the mammalian prion protein. Mol Biol Evol 20:111–121

    Article  PubMed  CAS  Google Scholar 

  30. Vassallo N, Herms J (2003) Cellular prion protein function in copper homeostasis and redox signalling at the synapse. J Neurochem 86:538–544

    Article  PubMed  CAS  Google Scholar 

  31. Weise J, Sandau R, Schwarting S, Crome O, Wrede A, Schulz-Schaeffer W, Zerr I, Bahr M (2006) Deletion of cellular prion protein results in reduced Akt activation, enhanced postischemic caspase-3 activation, and exacerbation of ischemic brain injury. Stroke 37:1296–1300

    Article  PubMed  CAS  Google Scholar 

  32. Wells GA, Hawkins SA, Austin AR, Ryder SJ, Done SH, Green RB, Dexter I, Dawson M, Kimberlin RH (2003) Studies of the transmissibility of the agent of bovine spongiform encephalopathy to pigs. J Gen Virol 84:1021–1031

    Article  PubMed  CAS  Google Scholar 

  33. Wells GA, Wilesmith JW, McGill IS (1991) Bovine spongiform encephalopathy: a neuropathological perspective. Brain Pathol 1:69–78

    PubMed  CAS  Google Scholar 

  34. Wilesmith JW, Ryan JB, Hueston WD (1992) Bovine spongiform encephalopathy: case-control studies of calf feeding practices and meat and bonemeal inclusion in proprietary concentrates. Res Vet Sci 52:325–331

    PubMed  CAS  Google Scholar 

  35. Wopfner F, Weidenhofer G, Schneider R, von Brunn A, Gilch S, Schwarz TF, Werner T, Schatzl HM (1999) Analysis of 27 mammalian and 9 avian PrPs reveals high conservation of flexible regions of the prion protein. J Mol Biol 289:1163–1178

    Article  PubMed  CAS  Google Scholar 

  36. Zanata SM, Lopes MH, Mercadante AF, Hajj GN, Chiarini LB, Nomizo R, Freitas AR, Cabral AL, Lee KS, Juliano MA, de Oliveira E, Jachieri SG, Burlingame A, Huang L, Linden R, Brentani RR, Martins VR (2002) Stress-inducible protein 1 is a cell surface ligand for cellular prion that triggers neuroprotection. Embo J 21:3307–3316

    Article  PubMed  CAS  Google Scholar 

  37. Zanusso G, Liu D, Ferrari S, Hegyi I, Yin X, Aguzzi A, Hornemann S, Liemann S, Glockshuber R, Manson JC, Brown P, Petersen RB, Gambetti P, Sy MS (1998) Prion protein expression in different species: analysis with a panel of new mAbs. Proc Natl Acad Sci USA 95:8812–8816

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

FDSS was a fellowship of INIA. This work was supported by the Spanish Ministry of Education and Science grants RC01-0605 and EET2002-05168.

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Correspondence to Alejandro Brun.

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Díaz-San Segundo, F., Salguero, F.J., de Ávila, A. et al. Distribution of the cellular prion protein (PrPC) in brains of livestock and domesticated species. Acta Neuropathol 112, 587–595 (2006). https://doi.org/10.1007/s00401-006-0133-1

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  • DOI: https://doi.org/10.1007/s00401-006-0133-1

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