NR AXIJ
AU Ayers,J.I.; Kincaid,A.E.; Bartz,J.C.
TI Prion Strain Targeting in the Central Nervous System
QU International Conference - Prion 2007 (26.-28.9.2007) Edinburgh International Conference Centre, Edinburgh, Scotland, UK - Book of Abstracts: Natural and Experimental Strains P02.08
IA http://www.prion2007.com/pdf/Prion Book of Abstracts.pdf
PT Konferenz-Poster
AB
Background: Prion strains are operationally defined by the regions of the central nervous system (CNS) where PrPsc, the prion disease specific isoform of the prion protein, accumulates. While it is known that prions are transynaptically transported along defined neuroanatomical pathways in the CNS, the mechanism responsible for prion strain targeting within the CNS is not known.
Objective: To investigate if prion strain targeting is due to differences in transport along neuroanatomical pathways.
Methods: Hamsters were inoculated in the sciatic nerve with either the hyper (HY) or drowsy (DY) strains of hamster-adapted transmissible mink encephalopathy (TME). Following inoculation with these two strains of TME, animals were sacrificed at selected time points postinfection. To determine the distribution of PrPsc within the CNS, immunohistochemistry was performed using a panel of monoclonal antibodies specific for the prion protein.
Results: In both strains of TME, sciatic nerve inoculation resulted in initial detection of PrPsc in ventral motor neurons of the lumbar spinal cord, ipsilateral to the side of inoculation, followed by retrograde transport of PrPsc via the corticospinal, rubrospinal, vestibulospinal, and reticulospinal descending motor tracts. PrPsc was not detected in neurons of the dorsal root ganglion prior to detection of PrPsc in the lumbar spinal cord. Both HY and DY PrPsc were detected in the neuropil with all antibodies tested, spanning from the N-terminal to C-terminal. Within the soma of neurons in lamina IX and the red nucleus HY PrPsc was only detected with antibodies C-terminal to the known HY TME PK cleavage site, whereas DY PrPsc was rarely detected in the soma of neurons.
Conclusion: These data suggest that differential transport along neuroanatomical pathways is not involved in prion strain targeting in the CNS, and that initial PrPsc transport is predominately, if not entirely, retrograde. This also suggests that once within the soma of neurons, HY and DY PrPsc may be differentially processed, which may lead to the differences observed between these two strains.
AD J. Ayers, J. Bartz, Creighton University, Department of Medical Microbiology and Immunology, USA; A. Kincaid, Creighton University, Department of Physical Therapy, USA
SP englisch
PO Schottland