The role of the homeobox gene family Otx in an ischemia/reperfusion damage in the enteric nervous system.

The homeobox gene family Otx encodes for transcription factors involved in the induction and morphogenesis of the neuroectoderm. Intestinal ischemia is an acute and rarely chronic clinical condition caused by the unbalance between intestinal oxygen supply and the metabolic tissue demand. After the remove of its cause, tissue re-oxygenation causes a series of biochemical and cellular mechanisms that amplify tissue damage. During intestinal I/R, nitric oxide can be both cryoprotective and cytotoxic based on the type of NOS involved in its synthesis. During this PhD project we have firstly studied the involvement of the Otx genes in a rat model of ischemia/reperfusion. Subsequently we replicated in vitro an I/R damage through the OGD procedure on a human neuroblastoma cell line previously treated with ATRA to induce its differentiation towards a neuronal-like phenotype. The data presented in this project clearly indicate the existence of an interplay between myenteric nitrergic pathways and Otx transcription factors that could sustain the development of motor alterations induced by NO after an I/R injury, with OTX1 and iNOS more related to the effects of I/R on the glial cells performing a cytotoxic effect while OTX2 and nNOS linked to the consequences on neuronal cells and developing a cytoprotective role.