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. 1982 Aug;75(8):618–624. doi: 10.1177/014107688207500809

Pathogenesis of mouse scrapie: patterns of agent replication in different parts of CNS following intraperitoneal infection1

R H Kimberlin, Carol A Walker
PMCID: PMC1438061  PMID: 6809940

Abstract

The dynamics of agent replication were studied at 8 levels of spinal cord and in 9 areas of brain of mice infected intraperitoneally with the 139A strain of scrapie agent. Replication in the CNS was first detectable at 2 levels of spinal cord between thoracic vertebrae 4 and 9. The onset of replication was progressively delayed by up to 4 weeks at increasingly lower levels of spinal cord. A similar trend was seen at higher levels of spinal cord and in brain. In brain, agent replication occurred first in medulla, then in the pons and midbrain, thalamus and hypothalamus and, finally, striatum, septum, hippocampus and cerebral cortex. These results are highly suggestive of spread of infection from peripheral sites of agent replication along autonomic fibres to midthoracic cord, followed by an ascending and descending spread of agent at an apparent rate of 0.5 to 1.0 mm/day until the whole CNS is infected. However, experiments involving sympathectomy gave inconclusive results and the evidence for neural spread of scrapie in the peripheral nervous system is circumstantial.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Angeletti P. U., Levi-Montalcini R. Sympathetic nerve cell destruction in newborn mammals by 6-hydroxydopamine. Proc Natl Acad Sci U S A. 1970 Jan;65(1):114–121. doi: 10.1073/pnas.65.1.114. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Black M. M., Lasek R. J. Slow components of axonal transport: two cytoskeletal networks. J Cell Biol. 1980 Aug;86(2):616–623. doi: 10.1083/jcb.86.2.616. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Broadwell R. D., Brightman M. W. Entry of peroxidase into neurons of the central and peripheral nervous systems from extracerebral and cerebral blood. J Comp Neurol. 1976 Apr 1;166(3):257–283. doi: 10.1002/cne.901660302. [DOI] [PubMed] [Google Scholar]
  4. Clarke M. C., Haig D. A. Multiplication of scrapie agent in mouse spleen. Res Vet Sci. 1971 Mar;12(2):195–197. [PubMed] [Google Scholar]
  5. Clarke M. C., Haig D. A. Presence of the transmissible agent of scrapie in the serum of affected mice and rats. Vet Rec. 1967 Apr 22;80(16):504–504. doi: 10.1136/vr.80.16.504. [DOI] [PubMed] [Google Scholar]
  6. Dickinson A. G., Fraser H. Scrapie: effect of Dh gene on incubation period of extraneurally injected agent. Heredity (Edinb) 1972 Aug;29(1):91–93. doi: 10.1038/hdy.1972.67. [DOI] [PubMed] [Google Scholar]
  7. Dickinson A. G., Meikle V. M., Fraser H. Genetical control of the concentration of ME7 scrapie agent in the brain of mice. J Comp Pathol. 1969 Jan;79(1):15–22. doi: 10.1016/0021-9975(69)90021-8. [DOI] [PubMed] [Google Scholar]
  8. Eklund C. M., Kennedy R. C., Hadlow W. J. Pathogenesis of scrapie virus infection in the mouse. J Infect Dis. 1967 Feb;117(1):15–22. doi: 10.1093/infdis/117.1.15. [DOI] [PubMed] [Google Scholar]
  9. Fink D. J., Gainer H. Retrograde axonal transport of endogenous proteins in sciatic nerve demonstrated by covalent labeling in vivo. Science. 1980 Apr 18;208(4441):303–305. doi: 10.1126/science.6154312. [DOI] [PubMed] [Google Scholar]
  10. Fraser H., Dickinson A. G. Pathogenesis of scrapie in the mouse: the role of the spleen. Nature. 1970 May 2;226(5244):462–463. doi: 10.1038/226462a0. [DOI] [PubMed] [Google Scholar]
  11. Fraser H., Dickinson A. G. Studies of the lymphoreticular system in the pathogenesis of scrapie: the role of spleen and thymus. J Comp Pathol. 1978 Oct;88(4):563–573. doi: 10.1016/0021-9975(78)90010-5. [DOI] [PubMed] [Google Scholar]
  12. Jacobs J. M., Macfarlane R. M., Cavanagh J. B. Vascular leakage in the dorsal root ganglia of the rat, studied with horseradish peroxidase. J Neurol Sci. 1976 Sep;29(1):95–107. doi: 10.1016/0022-510x(76)90083-6. [DOI] [PubMed] [Google Scholar]
  13. Jacobs J. M. Penetration of systemically injected horseradish peroxidase into ganglia and nerves of the autonomic nervous system. J Neurocytol. 1977 Oct;6(5):607–618. doi: 10.1007/BF01205222. [DOI] [PubMed] [Google Scholar]
  14. Johnson E. M., Jr, Cantor E., Douglas J. R., Jr Biochemical and functional evaluation of the sympathectomy produced by the administration of guanethidine to newborn rats. J Pharmacol Exp Ther. 1975 May;193(2):503–512. [PubMed] [Google Scholar]
  15. Kimberlin R. H., Walker C. A. Pathogenesis of mouse scrapie: dynamics of agent replication in spleen, spinal cord and brain after infection by different routes. J Comp Pathol. 1979 Oct;89(4):551–562. doi: 10.1016/0021-9975(79)90046-x. [DOI] [PubMed] [Google Scholar]
  16. Kimberlin R. H., Walker C. A. Pathogenesis of mouse scrapie: evidence for neural spread of infection to the CNS. J Gen Virol. 1980 Nov;51(Pt 1):183–187. doi: 10.1099/0022-1317-51-1-183. [DOI] [PubMed] [Google Scholar]
  17. Levi-Montalcini R., Angeletti P. U. Nerve growth factor. Physiol Rev. 1968 Jul;48(3):534–569. doi: 10.1152/physrev.1968.48.3.534. [DOI] [PubMed] [Google Scholar]
  18. Levi-Montalcini R., Angeletti P. U. Second symposium on catecholamines. Modification of sympathetic function. Immunosympathectomy. Pharmacol Rev. 1966 Mar;18(1):619–628. [PubMed] [Google Scholar]
  19. Manuelidis E. E., Gorgacs E. J., Manuelidis L. Viremia in experimental Creutzfeldt-Jakob disease. Science. 1978 Jun 2;200(4345):1069–1071. doi: 10.1126/science.349691. [DOI] [PubMed] [Google Scholar]
  20. Thoenen H., Tranzer J. P. Chemical sympathectomy by selective destruction of adrenergic nerve endings with 6-Hydroxydopamine. Naunyn Schmiedebergs Arch Exp Pathol Pharmakol. 1968;261(3):271–288. doi: 10.1007/BF00536990. [DOI] [PubMed] [Google Scholar]
  21. WIGHT P. A. The histopathology of the spinal cord in scrapie disease of sheep. J Comp Pathol. 1960 Jan;70:70–83. doi: 10.1016/s0368-1742(60)80006-9. [DOI] [PubMed] [Google Scholar]

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