Abstract
To investigate the amplifying potentialities of streptomycin sulfate in the immunohistochemical (IHC) detection of the abnormal prion protein (PrPsc), we used a sequential brain sampling from C506M3 scrapie strain inoculated C57Bl/6 mice. The weekly removed brains, from 7 to 63 days post intra-cranial inoculation were analysed using PrPsc IHC. The introduction of streptomycin sulfate, a technique developed for accurate cellular and regional mapping of PrPsc deposition in several animal TSEs, revealed a substantial amplifying effect and a clear specific PrPsc detection as early as 28 days post inoculation. The location of the first detected PrPsc deposits suggests a possible involvement of the cerebrospinal fluid in the early dissemination of the infectious agent. The meaning of these newly accessible PrPsc deposits is discussed in relation to a possible nascent form of PrPsc molecules detected in situ for the first time. Altogether, these findings argue that this method can be highly useful to study the early stages after infection with prion agents.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
Reference
Andreoletti O, Levavasseur E, Uro-Coste E, Tabouret G, Sarradin P, Delisle M-B, Berthon P, Salvayre R, Schelcher F, Negre-Salvayre A (2002) Astrocytes accumulate 4-hydroxynonenal adducts in murine scrapie and human creutzfeldt-jakob disease. Neurobiol Dis 11:386–393
Banks WA, Niehoff ML, Adessi C, Soto C (2004) Passage of murine scrapie prion protein across the mouse vascular blood-brain barrier. Biochem Biophys Res Commun 318:125–130
Bencsik A, Lezmi S, Baron T (2001) Autonomous nervous system innervation of lymphoid territories in spleen: A possible involvement of noradrenergic neurons for prion neuroinvasion in natural scrapie. J Neurol 7:447–453
Bencsik A, Coleman AW, Debeer SOS, Perron H, Moussa A (2006) Amplified immunohistochemical detection of PrPsc in animal transmissible spongiform encephalopathies using streptomycin. J Histochem Cytochem 54:849–853
Bendheim PE, Barry RA, DeArmond SJ, Stites DP, Prusiner SB (1984) Antibodies to a scrapie prion protein. Nature 310:418–420
Bolton DC, McKinley MP, Prusiner SB (1982) Identification of a protein that purifies with the scrapie prion. Science 218:1309–1311
Borchelt DR, Scott M, Taraboulos A, Stahl N, Prusiner SB (1990) Scrapie and cellular prion proteins differ in their kinetics of synthesis and topology in cultured cells. J Cell Biol 110:743–752
Brown DA, Bruce M, Fraser JR (2003) Comparison of the neuropathological characteristics of bovine spongiform encephalopathy (BSE) and variant Creutzfeldt-Jakob (vCJD) in mice. Neuropathol Appl Neurobiol 29:262–272
Bruce M (1996) In: Baker H, Ridley RM, Totowa NJ (eds) Strain typing studies of scrapie and BSE in prion diseases. Humana Press, Clifton, pp 223–236
Bruce ME, McConnell I, Fraser H, Dickinson AG (1991) The disease characteristics of different strains of scrapie in Sinc congenic mouse lines: implications for the nature of the agent and host control of pathogenesis. J Gen Virol 72:595–603
Bruce ME, Boyle A, Cousens S, McConnell I, Foster J, Goldmann W, Fraser H (2002) Strain characterization of natural sheep scrapie and comparison with BSE. J Gen Virol 83:695–704
DeArmond S, Yang S-L, Lee A, Bowler R, Taraboulos A, Groth D, Prusiner SB (1993) Three scrapie prion isolates exhibit different accumulation patterns of the prion protein scrapie isoform. Proc Natl Acad Sci USA 90:6449–6453
DeArmond SJ, Sanchez H, Yehiely F, Qiu Y, Ninchak-Casey A, Daggett V, Camerino AP, Cayetano J, Rogers M, Groth D et al (1997) Selective neuronal targeting in prion disease (in process citation). Neuron 19:1337–1348
Fraser H, Dickinson AG (1968) The sequential development of the brain lesion of scrapie in three strains of mice. J Comp Pathol 78:301–311
Fraser H, Dickinson AG (1970) Pathogenesis of scrapie in the mouse: the role of the spleen. Nature 226:462–463
Fraser H, Dickinson AG (1973) Scrapie in mice: agent-strain differences in the distribution and intensity of grey matter vacuolation. J Comp Pathol 83:29–40
Fraser JR (2002) What is the basis of transmissible spongiform encephalopathy induced neurodegeneration and can it be repaired? Neuropathol Appl Neurobiol 28:1–11
Gajdusek DC, Gibbs CJJ, Asher DM, Brown P, Diwan A, Hoffman P, Nemo G, Rohwer R, White L (1977) Precautions in medical care of, and in handling materials from, patients with transmissible virus dementia (Creutzfeldt-Jakob disease). New Engl J Med 297:1253–1258
Inoue Y, Yamakawa Y, Sakudo A, Kinumi T, Nakamura Y, Matsumoto Y, Saeki K, Kamiyama T, Onodera T, Nishijima M (2005) Infection route-independent accumulation of splenic abnormal prion protein. Jpn J Infect Dis 58:78–82
Jendroska K, Heinzel FP, Torchia M, Stowring L, Kretzschmar HA, Kon A, Stern A, Prusiner SB, DeArmond SJ (1991) Proteinase-resistant prion protein accumulation in Syrian hamster brain correlates with regional pathology and scrapie infectivity. Neurology 41:1482–1490
Kimberlin RH (1976) Experimental scrapie in the mouse: a review of an important model disease. Sci Progr 63:461–481
Kimberlin RH, Walker CA (1979) Pathogenesis of mouse scrapie: dynamics of agent replication in spleen spinal cord and brain after infection by different routes. J Comp Pathol 89:551
Kimberlin RH, Walker CA (1989) The role of the spleen in the neuroinvasion of scrapie in mice. Virus Res 12:201–211
Kocisko DA, Come JH, Priola SA, Chesebro B, Raymond GJ, Lansbury PT, Caughey B (1994) Cell-free formation of protease-resistant prion protein. Nature 370:471–474
Kretzschmar HA, Prusiner SB, Stowring LE, DeArmond SJ (1986) Scrapie prion proteins are synthesized in neurons. Am J Pathol 122:1–5
Lasmézas CI, Deslys JP, Demaimay R, Adjou KT, Hauw JJ, Dormont D (1996) Strain specific and common pathogenic events in murine models of scrapie and bovine spongiform encephalopathy. J Gen Virol 77:1601–1609
Leclere E, Perron H, Moussa A (2005) Prion2005: between fundamentals and society’s needs. Düsseldorf, Germany
Lezmi S, Bencsik A, Baron T (2006) PET-Blot analysis contributes to BSE strain recognition in C57Bl/6 mice. J Histochem Cytochem 54:1087–1094
Maignien T, Lasmezas CI, Beringue V, Dormont D, Deslys JP (1999) Pathogenesis of the oral route of infection of mice with scrapie and bovine spongiform encephalopathy agents. J Gen Virol 80(Pt 11):3035–3042
Millson GC, Kimberlin RH, Manning EJ, Collis S (1979) Early distribution of radioactive liposomes and scrapie infectivity in mouse tissues following administration by different routes. Vet Microbiol 4:89–99
Moussa A, Coleman AW, Perron H, Bencsik A, Leclere E, Martin A (2006) Use of streptomycin for precipitation and detection of Proteinase K resistant prion protein (PrPsc) in biological samples. Chem Commun 9:973–975
Oesch B, Westaway D, Prusiner SB (1991) Prion protein genes: evolutionary and functional aspects. Curr Top Microbiol Immunol 172:109–124
Pattison IH (1964) The spread of scrapie by contact between affected and healthy sheep, goats or mice. Vet Rec 76:333–336
Prusiner S, Scott M, Foster D, Pan KM, Groth D, Mirenda C, Torchia M, Yang SL, Serban D, Carlson GA et al (1990) Transgenetic studies implicate interactions between homologous PrP isoforms in scrapie prion replication. Cell 63:673–686
Prusiner SB (1982) Novel proteinaceous infectious particles cause scrapie. Science 216:136–144
Prusiner SB, Safar J, DeArmond SJ (2004) Transmission and replication of prions. In: Prusiner SB (ed) Prion biology and diseases, 2nd edn. Cold Spring Harbor Laboratory Press, New York, pp 187–242
Sales N, Rodolfo K, Hässig R, Faucheux B, Giamberardino LD, Moya KL (1998) Cellular prion protein localization in rodent and primate brain. Eur J Neurosci 10:2464–2471
Taraboulos A, Jendroska K, Serban D, Yang S-L, DeArmond SJ, Prusiner SB (1992a) Regional mapping of prion proteins in brain. Proc Natl Acad Sci USA 39:7620–7624
Taraboulos A, Raeber AJ, Borchelt DR, Serban D, Prusiner SB (1992b) Synthesis and trafficking of prion proteins in cultured cells. Mol Biol Cell 3:851–863
Tatzelt J, Prusiner SB, Welch WJ (1996) Chemical chaperones interfere with the formation of scrapie prion protein. EMBO J 15:6363–6373
Tatzelt J, Groth DF, Torchia M, Prusiner SB, DeArmond SJ (1999) Kinetics of prion protein accumulation in the CNS of mice with experimental scrapie. J Neuropathol Exp Neurol 58:1244–1249
Telling GC, Scott M, Mastrianni J, Gabizon R, Torchia M, Cohen FE, De Armond SJ, Prusiner SB (1995) Prion propagation in mice expressing human and chimeric prp transgenes implicates the interactions of cellular prp with another protein. Cell 83:79–90
Acknowledgments
The authors wish to thank Céline Raynaud, Mikaël Leboidre and Lionel Daudignon for their excellent histotechnical assistance, as well as Emilie Antier, Romain Godoye, Clément Lavigne, for animal care.
Author information
Authors and Affiliations
Corresponding author
Additional information
The work was done in the Histology Department of the Agents Transmissibles Non Conventionnels Unit of the Agence Française de Sécurité Sanitaire des Aliments—Lyon Laboratory.
Rights and permissions
About this article
Cite this article
Bencsik, A.A., Leclere, E., Perron, H. et al. New insights into early sequential PrPsc accumulation in scrapie infected mouse brain evidenced by the use of streptomycin sulfate. Histochem Cell Biol 129, 643–650 (2008). https://doi.org/10.1007/s00418-008-0382-2
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00418-008-0382-2