The enteric nervous system (ENS) plays a crucial role in regulating gastrointestinal (GI) functions, yet its complex morphology and functional connectivity in humans remain underexplored compared to animal models. This thesis aims to bridge this knowledge gap by investigating the ENS within the human intestine, focusing on its morphological characteristics, and potential implications for GI diseases.

The research is organized around two primary objectives: (a) conducting a histological analysis of the human ENS and (b) achieving 3D imaging of the ENS. To achieve these goals, the study will focus on the following tasks: identifying effective markers for labeling ENS neurons, characterizing the different types of plexuses within the intestine, elucidating the diverse cell types and their arrangements within these plexuses, analyzing the neurochemical codes of enteric neurons, comparing the labeling patterns of antibodies from different species, visualizing the 3D structure of the intestine, and mapping the spatial distribution of ENS networks in a 3D context.

A combination of immunohistochemical techniques, advanced imaging methods, and tissue-clearing protocols were employed to achieve these objectives. Our key findings include (i) the identification of reliable markers such as S100A and Beta III Tubulin for labeling different cell types in the plexus, detailed characterization of the myenteric and submucosal plexuses, and (ii) the successful application of 3D imaging techniques to reveal the intricate structure of the intestine and the ENS. The study also demonstrated distinct labeling patterns when using antibodies from different species, highlighting the importance of antibody specificity.

Our main results provide new insights into the 3D organization of the ENS within the human gut, with possible implications for understanding GI diseases such as irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD). The developed methodologies offer potential applications in clinical diagnostics and research, paving the way for more targeted therapeutic strategies. Future research could expand these findings by exploring other regions of the human gut and employing additional antibodies and imaging techniques to further elucidate the ENS’s role in health and disease.

Title	Published in	Access level	OA Policy	Year	Views	Downloads

Mapping the Functional and Morphological Architecture of Enteric Neural Networks in the Human Intestine: Insights into the Gut-Brain Connection				2024	24	1

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Rahsepar, Shima

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