NR AOQW
AU Burwinkel,M.; Schwarz,A.; Riemer,C.; Schultz,J.; van Landeghem,F.; Baier,M.
TI Rapid disease development in scrapie-infected mice deficient for CD40 Ligand
QU International Conference - Prion diseases: from basic research to intervention concepts - TSE-Forum, 08.10.-10.10.2003, Gasteig, München - Poster session - PG-06
PT Konferenz-Poster
AB
Several lines of evidence have implicated CD40-CD40 ligand interactions in the pathogenesis of neurodegenerative disorders and led to the suggestion to target CD40-CD40L interactions for therapeutic intervention. We studied the scrapie infection of CD40L deficient mice in comparison to wild type controls in order to address this question. All mice were intracerebrally inoculated with 20 µl of a 10-4 diluted 10% brain homogenate prepared from a terminally ill scrapie strain 139A infected mouse. CD40L(-/-) mice succumbed to the disease in average at 144±4 days post infection whereas the wild type controls died at 184±10 dpi. The highly significant (p<0.001) difference of 40 days in the survival of the two groups is equivalent to an infection of the CD40(-/-) mice with a 1000 times higher infectious dose as deduced from previously published dosis/incubation time relations. To characterize the scrapie infection in more detail we studied the gliosis, the accumulation of misfolded proteinase K-resistant prion protein , and the scrapie-associated vacuolization of the neuropil. No differences were seen for activated, GFAP-expressing, astrocytes and for the extent of PrPres deposition. Immunohistochemical detection of activated microglia with an anti-CD11b antibody revealed a more pronounced microgliosis in the scrapie-infected CD40(-/-) mice.In addition, the vacuolization of the neuropil was clearly more advanced in the CD40 deficient mice compared to the wild type controls.
Taken together our experimental model shows that a deficiency for CD40L is highly detrimental in prion diseases and our observations are in support of a concept which considers CD40-CD40L interactions as neuroprotective.
AD M. Burwinkel, A. Schwarz, C. Riemer, J. Schultz, M. Baier, Division Neurodegenerative Diseases, Robert Koch-Institute, Berlin, Germany; F. van Landeghem, Institute of Neuropathology, Humboldt University, Berlin, Germany
SP englisch
PO Deutschland