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Myenteric neurons of the ileum that express somatostatin are a target of prion neuroinvasion in an alimentary model of sheep scrapie

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Abstract

Neuroinvasion of the enteric nervous system by prions is an important step in dissemination to the brain, yet very little is known about the basic process of enteric neuroinvasion. Using an alimentary model of neonatal disease transmission, neuroinvasion by scrapie prions in the ileum of lambs was detected by immunohistochemical staining for the disease-associated form of the prion protein, PrPSc. Odds ratios (OR) were determined for the frequency of PrPSc staining within enteric somata categorized by plexus location (myenteric, submucosal) and neurochemical staining (PGP 9.5, neural nitric oxide synthase, somatostatin, substance P, and vasoactive intestinal polypeptide). PrPSc was observed in 4.48 ± 4.26% of myenteric neurons and 2.57 ± 1.82% of submucosal neurons in five lambs aged 208–226 days but not in a lamb aged 138 days. The relative frequency of PrPSc within enteric somata was interdependent on plexus location and neurochemical type. Interestingly, PrPSc was observed more frequently within myenteric neurons than in submucosal neurons (PGP 9.5; OR = 1.72, 95% confidence interval = 1.21–2.44), and was observed within the myenteric plexus approximately 4× (2.16–6.94) more frequently in somatostatin neurons than in the general neural population stained by PGP 9.5. Nerve fibers stained for somatostatin were present in the mucosa and near PrPSc staining within Peyer’s patches. The results suggest that somatostatin-expressing enteric neurons, with fiber projections near Peyer’s patches, but with somata present in greatest proportion within the myenteric plexus, are an early target for neuroinvasion by scrapie prions and could serve an important role in neural dissemination.

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Acknowledgments

We thank Tom Truscott for histological assistance; Duane Chandler, Alicia Ewing, Jim Reynolds, Caitlin Rizzo, and Ira Mickelsen for assistance with animal care and necropsy; and Bruce Mackey (USDA, Albany, CA) for statistical consultation. This work was paid for by CRIS 5348-32000-019-00D from the Agricultural Research Service, US Department of Agriculture. Lindsay Fry was supported by a summer research stipend from the Research Scholars Program, College of Veterinary Medicine, Washington State University. Mention of trade names or commercial products in this article is solely for the purpose of providing specific information and does not imply recommendation or endorsement by the US Department of Agriculture.

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Authors and Affiliations

  1. Animal Disease Research Unit, Agricultural Research Service, US Department of Agriculture, 3003 ADBF, WSU, PO Box 646630, Pullman, WA, 99164-6630, USA

    David A. Schneider, Stephen N. White & Katherine I. O’Rourke

  2. Department of Veterinary Microbiology and Pathology, Washington State University, Pullman, WA, 99164, USA

    Huijun Yan & Lindsay M. Fry

  3. Animal and Plant Health Inspection Service, Veterinary Services, US Department of Agriculture, Helena, MT, 59601, USA

    Janet Alverson

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  1. David A. Schneider
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  2. Huijun Yan
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Correspondence to David A. Schneider.

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Schneider, D.A., Yan, H., Fry, L.M. et al. Myenteric neurons of the ileum that express somatostatin are a target of prion neuroinvasion in an alimentary model of sheep scrapie. Acta Neuropathol 115, 651–661 (2008). https://doi.org/10.1007/s00401-008-0374-2

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  • DOI: https://doi.org/10.1007/s00401-008-0374-2

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