Enteric glial cells play a role in neuronal signalling and in inflammation in the gastrointestinal tract

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dc.contributor.advisorSharkey, Keith A.
dc.contributor.authorNasser, Yasmin
dc.date.accessioned2017-12-18T21:33:58Z
dc.date.available2017-12-18T21:33:58Z
dc.date.issued2007
dc.descriptionBibliography: p. 278-351en
dc.descriptionSome pages are in colour.en
dc.description.abstractThe functions of glial cells in the enteric nervous system remain poorly understood. We hypothesized that enteric glia play a role in enteric neurotransmission and in intestinal inflammation. Enteric glia may participate in neurotransmission as we observed that these cells expressed receptors for neurotransmitters, such as the metabotropic glutamate receptors (mGluR) 2/3 and 5, the a2a-adrenergic receptor and the somatostatin 2A (SSTR2A) receptor. Glial receptor expression was altered during colitis. We observed a redistribution in mGluR immunoreactivity in both trinitrobenzene sulphonic acid (TNBS) colitis in guinea pigs and dextran sodium sulphate (OSS) colitis in mice, while mGluR expression was decreased in the inflamed colons of interleukin-10 gene-deficient (I L-10-1-) mice. SSTR2A immunoreactivity was redistributed in mice given DSS but unchanged in IL-10-1- mice. No changes to enteric ganglia or glial fibrillary acidic protein expression were observed in DSS and IL-10_,_ mice. Stimulation of glial mGluR5 receptors increased the expression of the early immediate gene product, Fos, as well as the phosphorylated form of the extracellular signal-regulated kinase 1/2 (pERK1/2), but did not alter intracellular calcium, demonstrating that glial receptors were functionally activated. Studies in cultured enteric glia proved inconclusive, as their phenotype no longer resembled that in situ. The gliotoxin fluorocitrate specifically stimulated pERK1/2 expression in enteric glia and reduced ilea! motility in vitro and gastrointestinal transit in vivo. No changes in colonic transit or ion transport were observed, nor were there any signs of inflammation, suggesting that glia modulate the enteric neural circuits underlying gastrointestinal motility. Enteric glia of the mouse colon constitutively expressed the inducible nitric oxide synthase, likely due to "physiological" inflammation. The nitric oxide precursor, L-arginine was localized to neurons and glia in the mouse, suggesting that glial cells were not the sole source of L-arginine. No changes in gut transit or in the distribution of glial and neuronal markers were observed in mice deficient for the inducible L-arginine transporter. Taken together, these data demonstrate that enteric glia play a role in enteric neurotransmission, particularly in gastrointestinal motility and that changes in glial receptor expression are a feature of colitis.
dc.format.extentxix, 351 leaves : ill. ; 30 cm.en
dc.identifier.citationNasser, Y. (2007). Enteric glial cells play a role in neuronal signalling and in inflammation in the gastrointestinal tract (Doctoral thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca. doi:10.11575/PRISM/1745en_US
dc.identifier.doihttp://dx.doi.org/10.11575/PRISM/1745
dc.identifier.urihttp://hdl.handle.net/1880/102746
dc.language.isoeng
dc.publisher.institutionUniversity of Calgaryen
dc.publisher.placeCalgaryen
dc.rightsUniversity of Calgary graduate students retain copyright ownership and moral rights for their thesis. You may use this material in any way that is permitted by the Copyright Act or through licensing that has been assigned to the document. For uses that are not allowable under copyright legislation or licensing, you are required to seek permission.
dc.titleEnteric glial cells play a role in neuronal signalling and in inflammation in the gastrointestinal tract
dc.typedoctoral thesis
thesis.degree.disciplineNeuroscience
thesis.degree.grantorUniversity of Calgary
thesis.degree.nameDoctor of Philosophy (PhD)
ucalgary.item.requestcopytrue
ucalgary.thesis.accessionTheses Collection 58.002:Box 1740 520492257
ucalgary.thesis.notesUARCen
ucalgary.thesis.uarcreleaseyen
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