Metabolic Profiling of Prions In The Gastro-Intestinal Tract

<p><strong>Metabolic profiling of prions in the gastro-intestinal tract</strong><strong></strong></p> <p><strong>Uffaf Khan, B.S.</strong></p> <p><strong>Thesis Advisor: Claudio Soto, Ph.D.</strong></p> <p><strong>Abstract</strong></p> <p>Prion diseases, also known as transmissible spongiform encephalopathies (TSEs), are a group of debilitating neurodegenerative disorders that affect both humans and animals. They can be spread by horizontal transmission as seen in chronic wasting disease in deer and elk population. In addition, transmission to humans has also been documented which includes bovine spongiform encephalopathy in cattle to variant Creutzfeldt-Jakob disease in humans due to consumption of contaminated meat. The most probable natural route of transmission is by oral consumption of infectious material. Even though this mode of transmission has been known for a long time it is still unclear how the infectious material distributes <em>in vivo </em>shortly after ingestion and what is the metabolic stability in gastro-intestinal tissues. In this line, our hypothesis is that infectious prions resist gastro-intestinal digestion and directly cross the intestinal barrier after per-oral administration, distributing in blood and various organs. In order to test this hypothesis, we characterized the metabolic profile of prions in gastro-intestinal tract tissues by <em>in vitro</em> experiments and determined the initial distribution of infectious material within hours of ingestion <em>in vivo</em>. Our results showed the radiolabeled ¹²⁵I-PrP^Sc undergoes limited metabolic degradation -mostly in duodenum, jejunum and ileum tissue homogenates- as compared to stomach and colon homogenates where little degradation is observed. We have also separately shown that within two hours of oral ingestion of prions in mice self propagating prions are detected in blood, brain and various tissues.</p>

Name thesis:degree_name

Masters of Science (MS)

Level thesis:degree_level

Thesis (MS)

Year dc:date.available

2015

Author dc:creator

• Khan, Uffaf

Contributors dc:contributor

• Dr. Claudio Soto
• Dr. Jack Waymire
• Dr. Pramod Dash

• Prions
• TSE's
• scrapie
• PMCA
• radiolabeled prions
• Medicine and Health Sciences
• Neurosciences

Repository record dc:identifier

https://digitalcommons.library.tmc.edu/utgsbs_dissertations/624

OAI identifier oai:identifier

oai:digitalcommons.library.tmc.edu:utgsbs_dissertations-1659