NR ATQD
AU Ermolayev,V.; Klein,M.A.; Flechsig,E.
TI Reduction of retrogradely labelled rubrospinal neurons correlates with onset of clinical prion disease in mice
QU International Conference - Prion 2005: Between fundamentals and society's needs - 19.10.-21.10.2005, Congress Center Düsseldorf - Poster Session: Pathogenesis PATH-40
PT Konferenz-Poster
AB The presence of PrPsc and neuropathological features are typical hallmarks of prion diseases; however there is a broad variability of their manifestation in the brain. Onset of clinical disease is not necessarily correlated with the overall accumulation of PrPsc and pathology. Whereas in infected wild-type mice the increase in prion titer and PrPsc levels is followed within weeks by clinical disease, heterozygous mice harbour high levels of infectivity and PrPsc by 140 days, as did wild-type mice, but survive thereafter for at least another 140 days. Since pathology in the spinal cord appeared to be sufficient for disease in a transgenic model, we studied the correlation between integrity of spinal projecting neurons and the onset of disease by axonal tracing. Fast Blue (FB) was injected in the cervical spinal cord to label rubrospinal neurons of the Nucleus ruber a few days before onset of disease. Tga20 mice were infected into the right sciatic nerve targeting prions to the N. ruber on the contralateral side via its projecting rubrospinal tract. Mice developed disease after 72+5 days with paralysis of theirs right hind limbs, but prion-specific pathology was found bilaterally. Surprisingly, tracing revealed a 35% reduction of FB-labelled neurons (p=0.003) exclusively on the contralateral side. Similarly, intranervally inoculated C57BL/6 mice developed disease after 176+6 days with a similar phenotype and showed a 43% reduction of FB-labelled neurons (p=0.0002). In both cases, 100% labelling was found on the ipsilateral side, as in controls. After intracerebral inoculation of Tga20 mice, we found a 45% reduction of FB-labelled neurons bilaterally. In heterozygous mice, FB-labelled neurons were significantly reduced for 36% and 50% two months before and at disease onset, respectively. Taken together, we have shown that reduction of labelled rubrospinal neurons revealing the functional loss of brainstem neurons correlates with onset of prion disease in three lines.
AD V.Ermolayev, M.A.Klein, E.Flechsig, Emmy Noether Group, Institute of Virology and Immunobiology, University of Wuerzburg
SP englisch
PO Deutschland