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

Authors

David A. Schneider, U.S. Department of Agriculture
Huijun Yan, Washington State University
Lindsay M. Fry, Washington State UniversityFollow
Janet Alverson, U.S. Department of Agriculture
Stephen N. White, U.S. Department of AgricultureFollow
Katherine I. O'Rourke, U.S. Department of AgricultureFollow

Date of this Version

2008

Comments

Published in Acta Neuropathol (2008) 115:651–661

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, PrP^Sc. Odds ratios (OR) were determined for the frequency of PrP^Sc 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). PrP^Sc 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 PrP^Sc within enteric somata was interdependent on plexus location and neurochemical type. Interestingly, PrP^Sc 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