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Scrapie inoculation of mice: light and electron microscopy of the superior colliculi

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Summary

Ultrastructural examination of the superior colliculi of mice intraocularly inoculated with the ME7 strain of scrapie showed vacuolation early in the course of infection. Brains were examined between 85–260 days after monocular inoculation with scrapie. The mean incubation period for the development of clinical disease was 302 days. Vacuolation was seen initially in the contralateral superior colliculus and subsequently in the ipsilateral colliculus. In coded trails light microscopical vacuolation was seen from 218 days but ultrastructural examination showed that sparse vacuoles were inconsistently present in either or both of the ipsilateral and contralateral colliculi from 85 days; frequent vacuoles were seen from 190 days. Scrapie-induced vacuoles were differentiated from vacuoles present in control tissue by the presence of loculation or by a limiting double membrane which showed protrusion or proliferation of the innermost lamella. Vacuolation was seen in neuronal perikarya, myelinated fibres, dendrites and axonal presynaptic terminals. Vacuoles of myelinated fibres were observed within myelin and possibly also in the inner tongue of oligodendroglial cytoplasm. Whorled membrane configurations were also seen. Tubulovesicular particles, 40 nm in diameter, were recognised in two scrapie-infected mice. It is suggested that some scrapie vacuoles arise as a result of incorporation of abnormal membrane into organelles, possibly mitochondria, in neuronal perikarya and neurites and probably also within oligodendroglial cytoplasm and myelin.

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References

  1. Aiken JM, Williamson JL, Marsh RF (1989) Evidence of mitochondrial involvement in Scrapie infection. J Virol 63: 1686–1694

    Google Scholar 

  2. Baringer JR, Prusiner SB, Wong JS (1981) Scrapie-associated particles in post-synaptic processes. J Neuropathol Exp Neurol 40: 281–288

    Google Scholar 

  3. Beck E, Bak IJ, Christ JF, Gajdusek DC, Gibbs CJ, Hassler R (1975) Experimental kuru in the spider monkey: histopathological and ultrastructural studies of the brain during early stages of incubation. Brain 98: 595–612

    Google Scholar 

  4. Beck E, Daniel PM, Davey AJ, Gajdusek DC, Gibbs CJ (1982) The pathogenesis of transmissible spongiform encephalopathy. An ultrastructural study. Brain 105: 755–786

    Google Scholar 

  5. Bignami A, Parry HB (1972) Electron microscopic studies of the brain of sheep with natural scrapie. I The fine structure of neuronal vacuolation. Brain 95: 319–326

    Google Scholar 

  6. Bruce ME, Fraser H (1982) Focal and asymmetrical lesions in the brains of mice infected with certain strains of scrapie. Acta Neuropathol (Berl) 58: 133–140

    Google Scholar 

  7. Chandler RT (1967) Cytopathology of scrapie in the rat. An electron microscopic study of thalamic and hippocampal areas. Res Vet Sci 8: 98–112

    Google Scholar 

  8. Chou SM, Payne WM, Gibbs CJ, Gajdusek DC (1980) Transmission and scanning electron microscopy of spongiform change in Creutzfeldt-Jakob disease. Brain 103: 885–904

    Google Scholar 

  9. Clarke MC, Millson GC (1976) The membrane location of scrapie infectivity. J Gen Virol 31: 441–445

    Google Scholar 

  10. David-Farreira JF, David-Farreira KL, Gibbs CJ (1968) Scrapie in mice: ultrastructural observations in the cerebral cortex. Proc Soc Exp Biol Med 127: 313–320

    Google Scholar 

  11. Dickinson AG, Meikle VMH, Fraser H (1968) Identification of a gene which controls the incubation period of some strains of scrapie agent in mice. J Comp Pathol 78: 293–303

    Google Scholar 

  12. Ericsson JLE, Biberfeld P (1967) Studies on aldehyde fixation. Fixation rates and their relation to fine structure and some histochemical reactions in liver. Lab Invest 17: 281–298

    Google Scholar 

  13. Field EJ, Raine CS (1964) An electron microscopic study of scrapie in the mouse. Acta Neuropathol (Berl) 4: 200–211

    Google Scholar 

  14. Flament-Durand J, Couck AM (1979) Spongiform alterations in brain biopsies of presenile dementia. Acta Neuropathol (Berl) 46: 159–162

    Google Scholar 

  15. Fraser H (1976) The pathology of natural and experimental scrapie. In: Kimberlin RH (ed) Slow virus diseases of animals and man. North Holland, Amsterdam, pp 275–305

    Google Scholar 

  16. Fraser H (1979) The neuropathology of scrapie: the precision of the lesions and their diversity. In: Prusiner SB, Hadlow WJ (eds) Slow transmissible diseases of the nervous system. Academic Press, New York, pp 194–210

    Google Scholar 

  17. Fraser H (1982) Neuronal spread of scrapie agent and targeting of lesions within the retino-tectal pathway. Nature 295: 149–150

    Google Scholar 

  18. Fraser H, Dickinson AG (1968) The sequential development of the brain lesions in scrapie in three strains of mice. J Comp Pathol 83: 29–40

    Google Scholar 

  19. Fraser H, Dickinson AG (1985) Targeting of scrapie lesions and spread of agent via the retino-tectal projection. Brain Res 346: 32–41

    Google Scholar 

  20. Gibson PH, Doughty LA (1989) An electron microscopic study of inclusion bodies in synaptic terminals of scrapieinfected animals. Acta Neuropathol 77: 420–425

    Google Scholar 

  21. Gonatas NK, Terry RD, Weiss M (1965) Electron microscopic study in two cases of Creutzfeldt-Jakob disease. J Exp Neurol 24: 575–598

    Google Scholar 

  22. Gray EG (1986) Spongiform encephalopathy: a neurocytologist's viewpoint with a note on Alzheimer's disease. Neuropathol Appl Neurobiol 12: 149–172

    Google Scholar 

  23. Kidd M (1967) Some electron microscopical observations on status spongiosus. Acta Neuropoathol 35 [Suppl III]: 137–144

    Google Scholar 

  24. Kim JH, Manuelidis EE (1983) Ultrastructural findings in experimental Creutzfeld-Jakob disease in guinea pigs. J Neuropathol Exp Neurol 42: 29–43

    Google Scholar 

  25. Kim JH, Manuelidis EE (1986) Serial ultrastructural study of experimental Creutzfeldt-Jakob disease in guinea pigs. Acta Neuropathol (Berl) 69: 81–90

    Google Scholar 

  26. Lampert P, Hooks J, Gibbs CJ, Gajdusek DC (1971) Altered plasma membranes in experimental scrapie. Acta Neuropathol (Berl) 19: 81–93

    Google Scholar 

  27. Liberski PP, Asher DM, Yanagihara R, Gibbs CJ, Gajdusek DC (1989a) Serial ultrastructural studies of scrapie in hamsters. J Comp Pathol 101: 429–442

    Google Scholar 

  28. Liberski PP, Yanaghihara R, Gibbs CJ, Gajdusek DC (1989b) White matter ultrastructural pathology of experimental Creutzfeldt-Jakob disease in mice. Acta Neuropathol 79: 1–9

    Google Scholar 

  29. Millson GC, Hunter GD, Kimberlin RH (1971) An experimental examination of the scrapie agent in cell membrane mixtures. II The association of Scrapie activity with membrane fractions. J Comp Pathol 81: 255–265

    Google Scholar 

  30. Narang HK (1974) An electron microscopic study of natural scrapie sheep brain. Further observations on virus-like particles and paramyxovirus-like tubules. Acta Neuropathol (Berl) 28: 317–329

    Google Scholar 

  31. Narang HK, Asher DM, Pomeroy KL, Gajdusek DC (1987) Abnormal tubulovesicular particles in brains of hamsters with scrapie. Proc Soc Exp Biol Med 184: 504–509

    Google Scholar 

  32. Park TS, Kleinmann GM, Richardson EP (1980) Creutzfeldt-Jakob disease with extensive degeneration of white matter. Acta Neuropathol (Berl) 52: 239–242

    Google Scholar 

  33. Sasaki S, Mizoi S, Alashima A, Shinagawa M, Goto H (1986) Spongiform encephalopathy in sheep scrapie. Electron microscopic observations. Jpn J Vet Sci 48: 791–796

    Google Scholar 

  34. Sato Y, Ohta M, Tateishi J (1980) Experimental transmission of human subacute spongiform encephalopathy to small rodents. II Ultrastructural study of spongy state in the grey and white matter. Acta Neuropathol (Berl) 51: 135–140

    Google Scholar 

  35. Scott JR, Fraser H (1989) Enucleation after intraocular scrapie injection delays the spread of scrapie. Brain Res 504: 301–305

    Google Scholar 

  36. Smith TW, Anwer U, De Girolami U, Drachman DA (1987) Vacuolar change in Alzheimer's disease. Neurology 44: 1225–1228

    Google Scholar 

  37. Yagi H, Irino M, Matsushita T, Katoh S, Umezawa M, Tsuboyama T, Hosokawa M, Akiguchi I, Tokunaga R, Takeda T (1989) Spontaneous spongy degeneration of the brain stem in SAM-P#8 mice, a newly developed memory-deficient strain. J Neuropathol Exp Neurol 48: 577–589

    Google Scholar 

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Authors and Affiliations

  1. Lasswade Veterinary Laboratory, Bush Estate, EH26 OSA, Penicuik, Great Britain

    M. Jeffrey

  2. AFRC and MRC Neuropathogenesis Unit, West Mains Road, EH9 3JF, Edinburgh, Great Britain

    J. R. Scott & H. Fraser

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  1. M. Jeffrey
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  2. J. R. Scott
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  3. H. Fraser
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Jeffrey, M., Scott, J.R. & Fraser, H. Scrapie inoculation of mice: light and electron microscopy of the superior colliculi. Acta Neuropathol 81, 562–571 (1991). https://doi.org/10.1007/BF00310139

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  • DOI: https://doi.org/10.1007/BF00310139

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