Alteracions en la motilitat gastrointestinal degudes a neuropatia del sistema nerviós autònom i entèric basades en la diabetes mellitus

One opf the most important pathways that regulate gastrointestinal motility is the mechanisms involving excitation/contraction coupling or inhibition/relaxation coupling. These mechanisms are activated by intrinsic or extrinsic neural pathways allowing a proper coordination of gastrointestinal motility (gastric accommodation, migrating motor complex, peristaltic reflex, etc..) Patients with autoimmune diabtetes develop a peripheral neuropathy that impairs the gastrointestinal motor function. These patients show gastrointestinal symptoms such as (nausea, vomit, constipation, diarrea, etc...) At least part of this symptoms is due to the presence of a peripheral neuropathy that involves the automatic and enteric nervous system. A tansgenic mouse (RIP/IFN\betah) has been developed in the laboratory of Dra Fátima Bosch. These mice are an ideal model to study the diabetic neuropathy. A progressive destruction of pancreatic \beta cells occurs in these animals after administration of low doses of streptozotocin. A progressive increase of the blood glucose levels has been reported and after 3 to 5 months these animals show macroscopic alterations of the gastrointestinal tract (dilated stomach and colon). The main objective of this project is to study the physiopathology of the periphereal neuropaty based on the model of this transgenic mice. The study will be developes on three phases. In the first part, we will characterize the model studyding the histopathology of the peripheral neuropathy and the global alterations of gastrointestinal motility (gastric emptying and transit time). In the second phase we will study specific motor patterns such as migrating motor complexes, colonic motility and peristaltic reflex. Finally in the third approach we will focus on the impairmant of the relationship among neurons, ICC and muscle (release of neurotransmitters, pacemaker mechanisms ans impairment of smooth muscle function) (...)