FORPRION

BAVARIAN RESEARCH ASSOCIATION PRIONS

Wü 1 Pathogenesis of Prion Diseases III

The effect of mouse prions on primary neurons was studied on cultured motoneurons of embryonic mice. We found that cells developed a mouse prion-specific reduction in axon growth when exposed to moderate doses of prions, whereas their survival was only affected after treatment with high dose of prions. In collaboration with the group of Klein/Flechsig we have detected the pathological protein form (PrPSc) on cultured motoneurons, but further colocalisation studies are still underway. In a second project, we have shown that untreated motoneurons devoid of the cellular protein form (PrPC) showed a significant reduction of axon growth, but unaltered survival in comparisons to wild-type cells. The reduced axon growth was rescued by over expressing of PrPc in cells from transgenic PrP null mice. Our data suggests that cultured motoneurons are a new tool to study prion-induced axonal dysfunctions that are involved in the prion pathogenesis.