Characterization of enteric nervous system response to disease conditions in intestine

buir.advisorUzun, Bahar Değirmenci
dc.contributor.authorGönüllü, Nagihan Gizay
dc.date.accessioned2022-02-02T05:40:05Z
dc.date.available2022-02-02T05:40:05Z
dc.date.copyright2022-01
dc.date.issued2022-01
dc.date.submitted2022-01-31
dc.descriptionCataloged from PDF version of article.en_US
dc.descriptionThesis (Master's): Bilkent University, Department of Molecular Biology and Genetics, İhsan Doğramacı Bilkent University, 2022.en_US
dc.descriptionIncludes bibliographical references (leaves 50-57).en_US
dc.description.abstractSmall intestine is one of the vital organs in gastrointestinal tract that is responsible for absorption of food, amino acids and create barrier against microbial invasion. Whereas large bowel is involved in the reabsorption of water and minerals. Intestinal epithelium is a highly regenerative tissue that it can renew its cells in a span of 4-5 days. In homeostatic state, the turnover rate of the epithelial cells is stable however, in case of inflammation and disease, the rate of proliferation and differentiation increase to regenerate the damaged tissue. Primary cilia (PC) are non-motile, microtubule-based organelles that extrude from plasma membrane. It functions as a sensory element to detect environmental cues. One of the highly studied disease models is ulcerative colitis is mainly characterized by the inflammation of the intestinal mucosal layer and generated by DSS administration. Additionally, high fat diet induced obesity, as a metabolic disease model, was shown to affect intestinal stem cell activity such that higher fat composition of diet causes shortening of small intestine and decrease in weight of tissue. Enteric nervous system is the endogenous nervous network surrounding the gastrointestinal tract and it controls many vital functions including digestion, blood flow, intestinal motility. The initial aim of this study was to reveal the response of intestinal stem cell niche in those stated disease conditions. After detecting ACOT7 protein as a global marker for enteric nervous system of myenteric and submucosal plexus layers, we hypothesized that subpopulations of ENS cells have a connection with intestinal niche upon disease states. Our following goal was to identify subpopulations of ENS and ciliated cells. In order to assess our hypotheses, we conducted series of IHC experiments and confocal microscopy analyses. We found that ACOT7+ cells in ENS contain mainly distinct types of neuronal cell populations such as PHOX2B+ and HuCD+ cells. Further, we identified that glial cells are the main subpopulation of ENS changing their expression pattern in both colitis and obesity models. Also, we classified ciliated cells as a heterogenous population to be colocalized with several ENS and mesenchymal markers. Lastly, we analyzed the gut-brain axis response to DSS induced colitis in the brain of model animals with a focus on thalamus and insular cortex. We identified several thalamic regions showed similar expression pattern alterations which were observed in colon. Overall, the novelty of this thesis arises from the identification of ACOT7 as an ENS marker along with the detection of glial cell interaction with mesenchymal sub-populations. This interplay demonstrates a response upon disease states of both small intestine and colon.en_US
dc.description.provenanceSubmitted by Betül Özen (ozen@bilkent.edu.tr) on 2022-02-02T05:40:04Z No. of bitstreams: 1 Characterization of enteric nervous system response to disease conditions in intestine.pdf: 6479394 bytes, checksum: df63ee2935833ffe657d6285113106d0 (MD5)en
dc.description.provenanceMade available in DSpace on 2022-02-02T05:40:05Z (GMT). No. of bitstreams: 1 Characterization of enteric nervous system response to disease conditions in intestine.pdf: 6479394 bytes, checksum: df63ee2935833ffe657d6285113106d0 (MD5) Previous issue date: 2022-01en
dc.description.statementofresponsibilityby Nagihan Gizay Gönüllüen_US
dc.embargo.release2022-07-28
dc.format.extentix, 57 leaves, iv leaves : color illustrations ; 30 cm.en_US
dc.identifier.itemidB160751
dc.identifier.urihttp://hdl.handle.net/11693/76958
dc.language.isoEnglishen_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.subjectIntestineen_US
dc.subjectEnteric nervous systemen_US
dc.subjectACOT7en_US
dc.subjectStem cellen_US
dc.subjectNeuron and glial cellsen_US
dc.subjectPrimary ciliaen_US
dc.subjectObesityen_US
dc.subjectColitisen_US
dc.titleCharacterization of enteric nervous system response to disease conditions in intestineen_US
dc.title.alternativeEnterik sinir sisteminin bağırsakta hastalık durumlarına cevabının karakterizasyonuen_US
dc.typeThesisen_US
thesis.degree.disciplineMolecular Biology and Genetics
thesis.degree.grantorBilkent University
thesis.degree.levelMaster's
thesis.degree.nameMS (Master of Science)

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