1887

Abstract

The temporal course of cerebral cytokine gene expression was investigated in the ME7/CV murine scrapie model to determine any association with neuropathological events. Analysis by RNase protection assay (RPA) demonstrated no transcripts for ILs 2, 3, 4, 5, 6, 7, 10, 12p40 and 13, granulocyte macrophage colony-stimulating factor, IFN- or lymphotoxin- at any time during the course of this disease. Transcripts for transforming growth factor-1 were constitutively expressed in both control and scrapie-infected brain and were elevated at terminal disease. RPA and quantitative real-time RT-PCR detected low levels of transcripts for IL-1, IL-1 and TNF in scrapie-infected brain but only IL-1 was elevated consistently in all mice studied. Although glial cell activation within the hippocampus was evident from 100 days post-infection (p.i.), elevated IL-1 transcripts (and immunoreactivity) were evident from 180 days p.i., around the time of hippocampal pyramidal neuron loss, and increased steadily thereafter to reach a 3·5-fold increase at terminal disease. Even at their maximum, levels of these transcripts were disproportionately low relative to the degree of glial cell activation. It is concluded that cytokine gene expression in the ME7 scrapie-infected mouse brain, relative to the degree of reactive gliosis, is highly restricted, temporally late and disproportionately low.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/vir.0.19137-0
2003-09-01
2020-11-28
Loading full text...

Full text loading...

/deliver/fulltext/jgv/84/9/vir842605.html?itemId=/content/journal/jgv/10.1099/vir.0.19137-0&mimeType=html&fmt=ahah

References

  1. Amor S., Scallan M. F., Morris M. M., Dyson H., Fazakerley J. K.. 1996; Role of immune responses in protection and pathogenesis during Semliki Forest virus encephalitis. J Gen Virol77:281–291
    [Google Scholar]
  2. Badley J. E., Bishop G. A., St John T., Frelinger J. A.. 1988; A simple, rapid method for the purification of poly A+ RNA. Biotechniques6:114–116
    [Google Scholar]
  3. Baier M., Schultz J., Neidhold S., Simon D., Schwartz A.. 2002; Influence of interleukin-1 on astrocytosis and microgliosis during experimental scrapie infection of mice. International Conference on Transmissible Spongiform Encephalopathies (Edinburgh, UK: 15–18 September, 2002). Abstract 1.57
    [Google Scholar]
  4. Campbell I. L., Eddleston M., Kemper P., Oldstone M. B., Hobbs M. V.. 1994; Activation of cerebral cytokine gene expression and its correlation with onset of reactive astrocyte and acute-phase response gene expression in scrapie. J Virol68:2383–2387
    [Google Scholar]
  5. Cunningham C., Boche D., Perry V. H.. 2002; Transforming growth factor β 1, the dominant cytokine in murine prion disease: influence on inflammatory cytokine synthesis and alteration of vascular extracellular matrix. Neuropathol Appl Neurobiol28:107–119
    [Google Scholar]
  6. Fazakerley J. K., Pathak S., Scallan M., Amor S., Dyson H.. 1993; Replication of the A7(74) strain of Semliki Forest virus is restricted in neurons. Virology195:627–637
    [Google Scholar]
  7. Hobbs M. V., Weigle W. O., Noonan D. J., Torbett B. E., McEvilly R. J., Koch R. J., Cardenas G. J., Ernst D. N.. 1993; Patterns of cytokine gene expression by CD4+ T cells from young and old mice. J Immunol150:3602–3614
    [Google Scholar]
  8. Jeffrey M., Halliday W. G., Bell J., Johnston A. R., MacLeod N. K., Ingham C., Sayers A. R., Brown D. A., Fraser J. R.. 2000; Synapse loss associated with abnormal PrP precedes neuronal degeneration in the scrapie-infected murine hippocampus. Neuropathol Appl Neurobiol26:41–54
    [Google Scholar]
  9. Jeffrey M., Martin S., Barr J., Chong A., Fraser J. R.. 2001; Onset of accumulation of PrPres in murine ME7 scrapie in relation to pathological and PrP immunohistochemical changes. J Comp Pathol124:20–28
    [Google Scholar]
  10. Johnston A. R., Fraser J. R., Jeffrey M., MacLeod N.. 1998; Synaptic plasticity in the CA1 area of the hippocampus of scrapie-infected mice. Neurobiol Dis5:188–195
    [Google Scholar]
  11. Kim J. I., Ju W. K., Choi J. H., Choi E. K., Carp R. I., Wisniewski H. M., Kim Y. S.. 1999; Expression of cytokine genes and increased nuclear factor-kappa B activity in the brains of scrapie-infected mice. Brain Res Mol Brain Res73:17–27
    [Google Scholar]
  12. Kordek R., Nerurkar V. R., Liberski P. P., Isaacson S., Yanagihara R., Gajdusek D. C.. 1996; Heightened expression of tumor necrosis factor α , interleukin 1 α , and glial fibrillary acidic protein in experimental Creutzfeldt–Jakob disease in mice. Proc Natl Acad Sci U S A93:9754–9758
    [Google Scholar]
  13. Lucassen P. J., Williams A., Chung W. C., Fraser H.. 1995; Detection of apoptosis in murine scrapie. Neurosci Lett198:185–188
    [Google Scholar]
  14. Mabbott N. A., Williams A., Farquhar C. F., Pasparakis M., Kollias G., Bruce M. E.. 2000; Tumor necrosis factor α -deficient, but not interleukin-6-deficient, mice resist peripheral infection with scrapie. J Virol74:3338–3344
    [Google Scholar]
  15. Morgan T. E., Nichols N. R., Pasinetti G. M., Finch C. E.. 1993; TGF- β 1 mRNA increases in macrophage/microglial cells in the hippocampus in response to deafferentation and kainic acid-induced neurodegeneration. Exp Neurol120:291–301
    [Google Scholar]
  16. Park J. H., Shin S. H.. 1996; Induction of IL-12 gene expression in the brain in septic shock. Biochem Biophys Res Commun224:391–396
    [Google Scholar]
  17. Scott J. R., Fraser H.. 1984; Degenerative hippocampal pathology in mice infected with scrapie. Acta Neuropathol (Berl)65:62–68
    [Google Scholar]
  18. Walsh D. T., Betmouni S., Perry V. H.. 2001; Absence of detectable IL-1 β production in murine prion disease: a model of chronic neurodegeneration. J Neuropathol Exp Neurol60:173–182
    [Google Scholar]
  19. Williams A. E., Lawson L. J., Perry V. H., Fraser H.. 1994a; Characterization of the microglial response in murine scrapie. Neuropathol Appl Neurobiol20:47–55
    [Google Scholar]
  20. Williams A. E., van Dam A. M., Man-A-Hing W. K., Berkenbosch F., Eikelenboom P., Fraser H.. 1994b; Cytokines, prostaglandins and lipocortin-1 are present in the brains of scrapie-infected mice. Brain Res654:200–206
    [Google Scholar]
  21. Williams A., Lucassen P. J., Ritchie D., Bruce M.. 1997a; PrP deposition, microglial activation, and neuronal apoptosis in murine scrapie. Exp Neurol144:433–438
    [Google Scholar]
  22. Williams A., van Dam A. M., Ritchie D., Eikelenboom P., Fraser H.. 1997b; Immunocytochemical appearance of cytokines, prostaglandin E2 and lipocortin-1 in the CNS during the incubation period of murine scrapie correlates with progressive PrP accumulations. Brain Res754:171–180
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/vir.0.19137-0
Loading
/content/journal/jgv/10.1099/vir.0.19137-0
Loading

Data & Media loading...

Most cited this month Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error