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Journal of Virology, October 2001, p. 9320-9327, Vol. 75, No. 19
Neuropathogenesis Unit, Institute for Animal
Health, Edinburgh EH9 3JF, United
Kingdom,1 and Institut für
Neuropathologie, 81377 Munich,2 and
Robert Koch-Institut, 13353 Berlin,3
Germany
Received 19 March 2001/Accepted 11 June 2001
Although the ultimate target of infection is the central nervous
system (CNS), there is evidence that the enteric nervous system (ENS)
and the peripheral nervous system (PNS) are involved in the
pathogenesis of orally communicated transmissible spongiform encephalopathies. In several peripherally challenged rodent models of
scrapie, spread of infectious agent to the brain and spinal cord shows
a pattern consistent with propagation along nerves supplying the
viscera. We used immunocytochemistry (ICC) and paraffin-embedded tissue
(PET) blotting to identify the location and temporal sequence of
pathological accumulation of a host protein, PrP, in the CNS, PNS, and ENS of hamsters orally infected with the 263K scrapie strain.
Enteric ganglia and components of splanchnic and vagus nerve circuitry
were examined along with the brain and spinal cord. Bioassays were
carried out with selected PNS constituents. Deposition of pathological
PrP detected by ICC was consistent with immunostaining of a partially
protease-resistant form of PrP (PrPSc) in PET blots.
PrPSc could be observed from approximately one-third of the
way through the incubation period in enteric ganglia and autonomic
ganglia of splanchnic or vagus circuitry prior to sensory ganglia.
PrPSc accumulated, in a defined temporal sequence, in sites
that accurately reflected known autonomic and sensory relays. Scrapie
agent infectivity was present in the PNS at low or moderate levels. The
data suggest that, in this scrapie model, the infectious agent
primarily uses synaptically linked autonomic ganglia and efferent
fibers of the vagus and splanchnic nerves to invade initial target
sites in the brain and spinal cord.
0022-538X/01/$04.00+0 DOI: 10.1128/JVI.75.19.9320-9327.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
Early Spread of Scrapie from the Gastrointestinal
Tract to the Central Nervous System Involves Autonomic Fibers of the
Splanchnic and Vagus Nerves

*
Corresponding author. Mailing address: Institute for
Animal Health, Neuropathogenesis Unit, Ogston Building, West Mains Rd., Edinburgh EH9 3JF, United Kingdom. Phone: 44(0)131 667 5204. Fax: 44(0)131 668 3872. E-mail: tricia.mcbride{at}bbsrc.ac.uk.
Present address: Institute für Neuropathologie, 37075 Göttingen, Germany.
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