NR AXLQ
AU Ermolayev,V.; Cathomen,T.; Klein,M.A.; Flechsig,E.
TI Prion Disease is Associated with Impaired Axonal Transport of Spinal Cord Projecting Motor Neurons in Mice
QU International Conference - Prion 2007 (26.-28.9.2007) Edinburgh International Conference Centre, Edinburgh, Scotland, UK - Book of Abstracts: Pathology and Pathogenesis P03.79
IA http://www.prion2007.com/pdf/Prion Book of Abstracts.pdf
PT Konferenz-Poster
AB Prion diseases are fatal neurodegenerative disorders leading to motor dysfunction, dementia and death. They are accompanied by neuropathological changes, such as spongiosis, astrogliosis, and neuronal death. How prions proceed to damage neurons and whether dysfunctions in distinct brain areas are required for clinical disease is still unknown. Axonal transport of spinal cord projecting motor neurons in mouse cortex and the Red Nucleus (RN) was analyzed by injecting the tracer Fast blue (FB) into the cervical spinal cord. Upon intracerebral challenge with mouse RML prions, we found a significant reduction of FB-labelled neurons in the RN of wild-type and heterozygous mice as well as in mice expressing either wild-type PrP (Tga20) or truncated PrP (PrPf'32-93) shortly before the onset of clinical prion disease despite different incubation times. To show selective impairments of axonal transport, prions were applied into the right sciatic nerve to target the contralateral side of RN. A reduction of 37% and 43% was found exclusively on the targeted side of wild-type and Tga20 mice, respectively. Applying hamster prions to mice expressing hamster PrP by the same route, we confirmed the significant reduction demonstrating that prion-induced defects in the axonal transport are independent on the prion strain. Other tracing experiments with an AAV vector expressing a marker gene (AAV2-dsRed) injected into the hind limb muscle were performed for Tga20 and wild-type mice infected via the sciatic nerve. These revealed a reduction of tracer-positive neurons in the RN similar to FB. In infected wild-type mice we found a significant reduction of labelled motor neurons in the cortex. Quantitative analyses of brain sections for altered immunoreactivity of axonal markers are currently performed. Our data suggest that prion-induced impairments of the axonal transport in motor neurons located in the cortex and RN are associated with prion pathogenesis.
AD V. Ermolayev, M. Klein, E. Flechsig, Institute of Virology and Immunobiology, Germany; T. Cathomen, Charite Medical School, Institute of Infectious Diseases, Germany
SP englisch
PO Schottland