Abstract
Chronic wasting disease (CWD) is a fatal spongiform encephalopathy that is efficiently transmitted among members of the mammalian family Cervidae, including deer, elk, and moose. Typical of prion diseases, CWD is characterized by the conversion of the native protease-sensitive protein PrP C to a protease-resistant isoform, denoted PrP RES. In native species, spread of the disease likely results from the ingestion of prion-containing excreta, including urine, saliva, or feces. Although cervid prion protein-expressing transgenic [Tg(CerPrP)] mice have been shown to be effective surrogates of natural CWD, uncertainties remain regarding the mechanisms by which CWD prions traffic in vivo, including the manner by which CWD prions traffic from the gastrointestinal tract to the central nervous system. We used elk prion protein-expressing transgenic [Tg(CerPrP-E)] mice, infected by three different routes of inoculation, and tissue-based IHC to elucidate that centripetal and centrifugal CWD prion transit pathways involve cells and fibers of the autonomic nervous systems, including the enteric nervous system and central autonomic network. Moreover, we identified CWD PrP RES associated with the cell bodies and processes of enteric glial cells within the enteric nervous system of CWD-infected Tg(CerPrP-E) mice. The present findings demonstrate the importance of the peripheral and central autonomic networks in CWD neuroinvasion and neuropathogenesis and suggest that enteroglial cells may facilitate the shedding of prions via the intestinal tract.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1319-1328 |
| Number of pages | 10 |
| Journal | American Journal of Pathology |
| Volume | 179 |
| Issue number | 3 |
| DOIs | |
| State | Published - Sep 1 2011 |
| Externally published | Yes |
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Chronic wasting disease prion trafficking via the autonomic nervous system. / Seelig, Davis; Mason, Gary L.; Telling, Glenn C.; Hoover, Edward A.
In: American Journal of Pathology, Vol. 179, No. 3, 01.09.2011, p. 1319-1328.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Chronic wasting disease prion trafficking via the autonomic nervous system
AU - Seelig, Davis
AU - Mason, Gary L.
AU - Telling, Glenn C.
AU - Hoover, Edward A.
PY - 2011/9/1
Y1 - 2011/9/1
N2 - Chronic wasting disease (CWD) is a fatal spongiform encephalopathy that is efficiently transmitted among members of the mammalian family Cervidae, including deer, elk, and moose. Typical of prion diseases, CWD is characterized by the conversion of the native protease-sensitive protein PrP C to a protease-resistant isoform, denoted PrP RES. In native species, spread of the disease likely results from the ingestion of prion-containing excreta, including urine, saliva, or feces. Although cervid prion protein-expressing transgenic [Tg(CerPrP)] mice have been shown to be effective surrogates of natural CWD, uncertainties remain regarding the mechanisms by which CWD prions traffic in vivo, including the manner by which CWD prions traffic from the gastrointestinal tract to the central nervous system. We used elk prion protein-expressing transgenic [Tg(CerPrP-E)] mice, infected by three different routes of inoculation, and tissue-based IHC to elucidate that centripetal and centrifugal CWD prion transit pathways involve cells and fibers of the autonomic nervous systems, including the enteric nervous system and central autonomic network. Moreover, we identified CWD PrP RES associated with the cell bodies and processes of enteric glial cells within the enteric nervous system of CWD-infected Tg(CerPrP-E) mice. The present findings demonstrate the importance of the peripheral and central autonomic networks in CWD neuroinvasion and neuropathogenesis and suggest that enteroglial cells may facilitate the shedding of prions via the intestinal tract.
AB - Chronic wasting disease (CWD) is a fatal spongiform encephalopathy that is efficiently transmitted among members of the mammalian family Cervidae, including deer, elk, and moose. Typical of prion diseases, CWD is characterized by the conversion of the native protease-sensitive protein PrP C to a protease-resistant isoform, denoted PrP RES. In native species, spread of the disease likely results from the ingestion of prion-containing excreta, including urine, saliva, or feces. Although cervid prion protein-expressing transgenic [Tg(CerPrP)] mice have been shown to be effective surrogates of natural CWD, uncertainties remain regarding the mechanisms by which CWD prions traffic in vivo, including the manner by which CWD prions traffic from the gastrointestinal tract to the central nervous system. We used elk prion protein-expressing transgenic [Tg(CerPrP-E)] mice, infected by three different routes of inoculation, and tissue-based IHC to elucidate that centripetal and centrifugal CWD prion transit pathways involve cells and fibers of the autonomic nervous systems, including the enteric nervous system and central autonomic network. Moreover, we identified CWD PrP RES associated with the cell bodies and processes of enteric glial cells within the enteric nervous system of CWD-infected Tg(CerPrP-E) mice. The present findings demonstrate the importance of the peripheral and central autonomic networks in CWD neuroinvasion and neuropathogenesis and suggest that enteroglial cells may facilitate the shedding of prions via the intestinal tract.
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UR - http://www.scopus.com/inward/citedby.url?scp=80052841081&partnerID=8YFLogxK
U2 - 10.1016/j.ajpath.2011.05.057
DO - 10.1016/j.ajpath.2011.05.057
M3 - Article
C2 - 21777560
AN - SCOPUS:80052841081
VL - 179
SP - 1319
EP - 1328
JO - American Journal of Pathology
JF - American Journal of Pathology
SN - 0002-9440
IS - 3
ER -