Gangliosides and GDNF pathway in diabetic small intestine

SÁNCHEZ M.N.; HONORÉ S.M.; GENTA S.B.; SÁNCHEZ S.S.

Mar del Plata, Buenos Aires, Argentina

Congreso; XLIII Anual Meeting Sociedad Argentina de Investigacion en Bioquímica y Biología Molecular; 2007

Sociedad Argentina de Investigacion en Bioquímica y Biología Molecular

Chronic diabetes gives rise to multiple complication including those of gastrointestinal tract. Diabetic intestinal motility dysfunction is associated with pathologicallesions that occur in the enteric neurons. However the mechanisms underlying these changes in the enteric nervous system are not well defined. Gangliosides (Gls), sialic acid-containing glicoesphingolipids are present at cell surface. Recent studies indicate that they are implicated in many biological functions including cell-cell interaction, cell activation, and signal transduction through modulation of growth factors. In addition GIs play role in neuron survival and death. In this study we investigated the pattem ofGls and GDNF/GFRal-Ret signal pathway in the small intestine of diabetic mice. Samples were analyzed by TUNEL, irnmunohistochemistry, thin layer chromatography and RT-PCR. A significantly increase of apoptotic cells was observed at the myenteric plexus level of diabetic animals. AIso we observed quantitative and qualitative changes in the pattem of intestinal GIs. Diabetes produces a significant decrease in GDla, GD3, GMl and an increase expression of GM3. Semi-quantitative variations on GDNF/GFRal-Ret rnRNA levels were observed under diabetic state. In conclusion we suggest that the impairment of enteric neurons could be mediated by alterations in both GLs pattem and in consonance with GDNF pathway.