Browsing by Subject "Neuron and glial cells"

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Open Access
Characterization of enteric nervous system response to disease conditions in intestine
(2022-01) Gönüllü, Nagihan Gizay
Small 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.