Region-dependent histological and molecular damage in the gut wall affecting the intestinal neuro-immune interactions in the streptozotocin diabetic rats
Thesis supervisor: Nikolett Bódi
Location of studies (in Hungarian): University of Szeged, Department of Physiology, Anatomy and Neuroscience Abbreviation of location of studies: SzTE
Description of the research topic:
Growing amount of evidence has indicated that molecular differences in the neuronal microenvironment are critical in the pathogenesis of intestinal region-specific diabetic enteric neuropathy.
Using a streptozotocin-induced diabetic rat model we recently demonstrated that nitrergic myenteric neurons, which are key regulators of peristalsis, the endothelium of mesenteric capillaries supplying these neurons, the faeces- and mucosa-associated intestinal microbiota, the endogenous heme oxygenase system and also the oxidative status display different susceptibilities to diabetic damage and also to insulin treatment in the different gut segments.
Therefore, the main focus of the present proposal relates to how the different inflammatory cytokines and toll-like receptors can regulate the neuro-immune interactions in the different intestinal segments in diabetes.
Considering the complexity of this question, we are planning a comprehensive study using histological, quantitative immunohistochemical, electron microscopic and molecular methods in different cellular compartments (enterocytes, immune cells, myenteric and submucous neurons) and tissue homogenates of different gut segments of control, streptozotocin-induced diabetic and insulin-treated diabetic rats to clear:
1/ Are there any gut segment-specific changes in the expression of different pro-inflammatory cytokines like tumor necrosis factor alpha and interleukins and their receptors?
2/ Which regional differences can be observed in the expression of different toll-like receptors in the epithelium and different immune cells of mucosa and enteric neurons?
Required language skills: English B2 Recommended language skills (in Hungarian): English B2 Further requirements: - MSc (biologist, biology teacher, veterinarian)/MD degree,
- Practice in histological and immunohistochemical techniques.