Dissertation
CONTRIBUTION OF TRPV1 VAGAL AFFERENT NEURONS IN THE DETECTION OF PATHOGENIC BACTERIAL COLONIZATION IN THE GUT: PUTATIVE ROLE(S) OF PRO-INFLAMMATORY CYTOKINES
Doctor of Philosophy (PhD), Washington State University
01/2012
Handle:
https://hdl.handle.net/2376/4174
Abstract
Vagal efferent activation can reduce inflammation and disease activity in various animal models of intestinal inflammation, likely via a mechanism involving activation of a a7nAChR subtype. The current hypothesis for this pathway (termed the cholinergic anti-inflammatory pathway) suggests vagal efferent inflammatory inhibition is dependent on vagal afferent stimulation. However, little is known about what leads to afferent activation and what fiber type is responsible for transmitting this information to the brain especially in the context of subclinical or clinical pathogenic bacteria. To address these questions, we first determined if selectively lesioning vagal afferents altered c-Fos expression in the nucleus of the solitary tract (nTS) or altered animal survival after mice were either inoculated with Campylobacter jejuni (C. jejuni) or Salmonella typhimurium (S. typhimurium). Our results demonstrate intraluminal pathogenic bacteria induced nTS activation is dependent on intact, capsaicin sensitive vagal afferents. We also found that lesioning vagal afferents changes the survival dynamics of S. typhimurium inoculated animals but has no effect on C. jejuni inoculated animals. We next determined what possible inflammatory mediators could lead to the observed in vivo increase in nTS activation. To do this we used in vitro calcium imaging and found the pro-inflammatory mediators tumor necrosis factor alpha (TNFa;) and lipopolysaccharide (LPS) directly activated cultured vagal afferent neurons. We also found that the TNFa; and LPS sensitive neurons occurred primarily on capsaicin sensitive neurons. Additionally we found that pre-incubation with TNFa; had no affect on the response rate to cholecystokinin-8 but did increase the sensitivity and response rate to serotonin. Through this work, we concluded that nTS detection of pathogenic bacteria in the gut is dependent on capsaicin sensitive (TRPV1) vagal afferent neurons, inflammatory mediators that may activate this pathway are TNFa; and/or LPS, and chronic exposure to TNFa; may increase the sensitivity to other gut peptides.
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Details
- Title
- CONTRIBUTION OF TRPV1 VAGAL AFFERENT NEURONS IN THE DETECTION OF PATHOGENIC BACTERIAL COLONIZATION IN THE GUT
- Creators
- Timothy Paul Riley
- Contributors
- Steven M Simasko (Advisor)Robert C Ritter (Committee Member)Krzysztof Czaja (Committee Member)Richard C Rogers (Committee Member)
- Awarding Institution
- Washington State University
- Academic Unit
- Program in Neuroscience
- Theses and Dissertations
- Doctor of Philosophy (PhD), Washington State University
- Number of pages
- 135
- Identifiers
- 99900581748701842
- Language
- English
- Resource Type
- Dissertation