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Autonomous nervous system innervation of lymphoid territories in spleen: A possible involvement of noradrenergic neurons for prion neuroinvasion in natural scrapie

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Abstract

In experimental as well as in natural scrapie, transmissible spongiform encephalopathies (TSEs), the infectious agent, closely related to PrPsc, an abnormal isoform of the cellular prion protein, invades and replicates in lymphoid organs such as spleen before affecting the brain. To clarify the cellular requirements for the possible neuroinvasion of scrapie agent from the spleen to the central nervous system, we have studied the sympathetic innervation within the lymphoid territories of the spleen. These noradrenergic fibers originating from the coeliomesenteric ganglia were examined with regard to PrPsc-associated cells in spleen of adult sheep severely affected with natural scrapie. Using a double immunolabelling strategy, we demonstrated the proximity of noradrenergic endings with PrPsc-accumulating cells, strengthening its possible implication in the neuroinvasion process.

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References

  • Aguzzi A (1997). Neuro-immune connection in spread of prions in the body? Lancet 349: 742–743.

    Article  CAS  PubMed  Google Scholar 

  • Andréoletti O, Berthon P, Marc D, Sarradin P, Grosclaude J, Van Keulen L, Schelcher F, Elsen J, Lantier F (2000). Early accumulation of PrPsc in gut-associated lymphoid and nervous tissues of susceptible sheep from a Romanov flock with natural scrapie. J Gen Virol 81: 3115–3126.

    PubMed  Google Scholar 

  • Baldauf E, Beekes M, Diringer H (1997). Evidence for an alternative direct route of access for the scrapie agent to the brain bypassing the spinal cord. J Gen Virol 78: 1187–1197.

    CAS  PubMed  Google Scholar 

  • Beekes M, Baldauf E, Diringer H (1996). Sequential appearance and accumulation of pathognomonic markers in the central nervous system of hamsters orally infected with scrapie. J Gen Virol 77: 1925–1934.

    Article  CAS  PubMed  Google Scholar 

  • Beekes M, McBride P, Baldauf E (1998). Cerebral targeting indicates vagal spread of infection in hamsters fed with scrapie. J Gen Virol 79: 601–607.

    CAS  PubMed  Google Scholar 

  • Bell JE, Gentleman SM, Ironside JW, McCardle L, Lantos PL, Doey L, Lowe J, Fergusson J, Luthert P, McQuaid S, Allen IV (1997). Prion protein immunocytochemistry — UK five centre consensus report. Neuropathol Appl Neurobiol 23: 26–35.

    Article  CAS  PubMed  Google Scholar 

  • Bencsik A, Lezmi S, Hunsmann G, Baron T (2001). Close vicinity of PrP expressing cells (FDC) with noradrenergic fibers in healthy sheep spleen. Dev Immunol in press.

  • Björklund A, Hökfelt T (1985). Handbook of chemical neuroanatomy—Classical transmitters in the CNS Vol. 2, Elsevier, Amsterdam.

    Google Scholar 

  • Bolton DC, McKinley MP, Prusiner SB (1982). Identification of a protein that purifies with the scrapie prion. Science 218: 1309–1311.

    Article  CAS  PubMed  Google Scholar 

  • Bossers A, Schreuder BEC, Muileman IH, Belt PBG, Smits MA (1996). PrP genotype contributes to determining survival times of sheep with natural scrapie. J Gen Virol 77: 2669–2673.

    Article  CAS  PubMed  Google Scholar 

  • Bruce ME, Brown KL, Mabbott NA, Farquhar CF, Jeffrey M (2000). Follicular dendritic cells in TSE pathogenesis. Immunol Today 21: 442–446.

    Article  CAS  PubMed  Google Scholar 

  • Elsen J-M, Amigues Y, Schelcher F, Ducrocq V, Andréoletti O, Eychenne F, Vu Tien Khang J, Poivey J-P, Lantier F, Laplanche J-L (1999). Genetic susceptibility and transmission factors in scrapie: Detailed analysis of an epidemic in a closed flock of Romanov. Arch Virol 144: 431–445.

    Article  CAS  PubMed  Google Scholar 

  • Feiten DL, Feiten S (1988). Sympathetic noradrenergic innervation of immune organs. Brain Behav Immun 2: 293–300.

    Article  Google Scholar 

  • Fraser H (1970). Pathogenesis of scrapie in the mouse: The role of spleen. Nature 226: 462–463.

    Article  CAS  PubMed  Google Scholar 

  • Fried G, Terenius L, Brodin E, Efendic S, Dockray J, Fahrenkrug J, Goldstein M, Hökfelt T (1986). Neuropeptide Y, enkephalin and noradrenaline coexist in sympathetic neurons innervating the bovine spleen. Biochemical and immunohistochemical evidence. Cell Tissue Bes 243: 495–508.

    CAS  Google Scholar 

  • Glatzel M, Aguzzi A (2000). PrP(c) expression in the peripheral nervous system is a determinant of prion neuroinvasion. J Gen Virol 81: 2813–2821.

    CAS  PubMed  Google Scholar 

  • Groschup MH, Beekes M, McBride PA, Hardt M, Hainfellner JA, Budka H (1999). Deposition of disease-associatedprion protein involves the peripheral nervous system in experimental scrapie. Acta Neuropathol 98: 453–457.

    Article  CAS  PubMed  Google Scholar 

  • Hadlow WJ, Kennedy RC, Race RE (1982). Natural infection of Suffolk sheep with scrapie virus. J Infect Dis 146: 657–664.

    CAS  PubMed  Google Scholar 

  • Heggebo R, Press CM, Gunnes G, Inge Lie K, Tranulis MA, Ulvund M, Groschup MH, Landsverk T (2000). Distribution of prion protein in the ileal Peyer’s patch of scrapie-free lambs and lambs naturally and experimentally exposed to the scrapie agent. J Gen Virol 81: 2327–2337.

    CAS  PubMed  Google Scholar 

  • Hirokawa N (1997). The mechanisms of fast and slow transport in neurons: Identification and characterization of the new kinesin superfamily motors. Curr Opin Neurobiol 7: 605–614.

    Article  CAS  PubMed  Google Scholar 

  • Houston F, Foster JD, Chong A, Hunter N, Bostock CJ (2000). Transmission of BSE by blood transfusion in sheep. Lancet 356: 999–1000.

    Article  CAS  PubMed  Google Scholar 

  • Hunter N, Foster JD, Goldmann W, Stear MJ, Hope J, Bostock C (1996). Natural scrapie in a closed flock of Cheviot sheep occurs only in specific PrP genotypes. Arch Virol 141: 809–824.

    Article  CAS  PubMed  Google Scholar 

  • Hunter N, Goldmann W, Marshall E, O’Neill G (2000). Sheep and goats: Natural and experimental TSEs and factors influencing incidence of disease. Arch Virol Suppl 16: 181–188.

    PubMed  Google Scholar 

  • Hunter N, Moore L, Hosie BD, Dingwall WS, Greig A (1997). Association between natural scrapie and PrP genotype in a flock of Suffolk sheep in Scotland. Vet Rec 140: 59–63.

    Article  CAS  PubMed  Google Scholar 

  • Kimberlin RH, Field HJ, Walker CA (1983a). Pathogenesis of mouse scrapie: Evidence for spread of infection from central to peripheral nervous system. J Gen Virol 64: 713–716.

    Article  PubMed  Google Scholar 

  • Kimberlin RH, Hall SM, Walker CA (1983b). Pathogenesis of mouse scrapie: Evidence for direct neural spread of infection to the CNS after injection of sciatic nerve. J Neurol Sci 61: 315–325.

    Article  CAS  PubMed  Google Scholar 

  • Kimberlin RH, Walker CA (1988). Incubation periods in six models of intraperit one ally injected scrapie depend mainly on the dynamics of agent replication within the nervous system and not the lymphoreticular system. J Gen Virol 69: 2953–2960.

    Article  PubMed  Google Scholar 

  • Klein MA, Frigg R, Flechsig E, Raeber AJ, Kalinke U, Bluethmann H, Bootz F, Suter M, Zinkernagel RM, Aguzzi A (1997). A crucial role for B cells in neuroinvasive scrapie. Nature 390: 687–690.

    CAS  PubMed  Google Scholar 

  • Krasemann S, Groschup M, Harmeyer S, Hunsmann G, Bodemer W (1996). Generation of monoclonal antibodies against human prion proteins in PrP0/0-mice. Mol Med 2: 725–734.

    CAS  PubMed  Google Scholar 

  • Lasmezas CI, Cesbron JY, Deslys JP, Demaimay R, Adjou KT, Rioux R, Lemaire C, Locht C, Dormont D (1996). Immune system-dependent and -independent replication of the scrapie agent. J Virol 70: 1292–1295.

    CAS  PubMed  Google Scholar 

  • Mouillet-Richard S, Ermonval M, Chebassier C, Laplanche JL, Lehmann S, Launay JM, Kellermann O (2000). Signal transduction through prion protein. Science 289: 1925–1928.

    Article  CAS  PubMed  Google Scholar 

  • O’Rourke KI, Baszler TV, Besser TE, Miller JM, Cutlip RC, Wells GA, Ryder SJ, Parish SM, Hamir AN, Cockett NE, Jenny A, Knowles DP (2000). Preclinical diagnosis of scrapie by immunohistochemistry of third eyelid lymphoid tissue. J Clin Microbiol 38: 3254–3259.

    PubMed  Google Scholar 

  • O’Rourke KI, Baszler TV, Parish SM, Knowles DP (1998). Preclinical detection of PrPsc in nictitating membrane lymphoid tissue of sheep. Vet Rec 142: 489–491.

    Article  PubMed  Google Scholar 

  • Prusiner SB (1997). Prion diseases and the BSE crisis. Science 278: 245–251.

    Article  CAS  PubMed  Google Scholar 

  • Race R, Jenny A, Sutton D (1998). Scrapie infectivity and proteinase K-resistant prion protein in sheep placenta, brain, spleen, and lymph node: Implications for transmission and antemortem diagnosis. J Infect Dis 178: 949–953.

    Article  CAS  PubMed  Google Scholar 

  • Saez JC, Branes MC, Corvalan H, Eugenin EA, Gonzales H, Martinez AD, Palisson F (2000). GAP junction in cells of the immune system: Structure, regulation and possible functional role. Braz J Med Biol Res 33: 447–455.

    Article  CAS  PubMed  Google Scholar 

  • Somerville RA, Birkett CR, Farquhar CF, Hunter N, Goldmann W, Dornan J, Grover D, Hennion RM, Percy C, Foster J, Jeffrey M (1997). Immunodetection of PrPsc in spleens of some scrapie-infected sheep but not BSE-infected cows. J Gen Virol 9: 2389–2396.

    Google Scholar 

  • van Keulen LJM, Schreuder BEC, Meloen RH, Mooij-Harkes G, Vromans MEW, Langeveld JPM (1996). Immunohistochemical detection of prion in lymphoid tissues of sheep with natural scrapie. J Clin Microbiol 34: 1228–1231.

    PubMed  Google Scholar 

  • van Keulen LJM, Schreuder BEC, Vromans MEW, Langeveld JPM, Smits MA (1999). Scrapie-associated prion protein in the gastro-intestinal tract of sheep with natural scrapie. J Comp Pathol 121: 55–63.

    Article  PubMed  Google Scholar 

  • van Keulen LJM, Schreuder BEC, Vromans MEW, Langeveld JPM, Smits MA (2000). Pathogenesis of natural scrapie in sheep. Arch Virol Suppl 16: 57–71.

    PubMed  Google Scholar 

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Correspondence to Anna Bencsik.

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Bencsik, A., Lezmi, S. & Baron, T. Autonomous nervous system innervation of lymphoid territories in spleen: A possible involvement of noradrenergic neurons for prion neuroinvasion in natural scrapie. Journal of NeuroVirology 7, 447–453 (2001). https://doi.org/10.1080/135502801753170309

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  • DOI: https://doi.org/10.1080/135502801753170309

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