Induction of VGF mRNA in neurons of the rat nucleus tractus solitarius and the dorsal motor nucleus of vagus in duodenal ulceration by cysteamine.
To investigate the possible role of the brainstem in cysteamine-induced peptic ulceration, we examined the expression of VGF mRNA, which is induced in PC12 cells following application of nerve growth factor [23], in the nucleus tractus solitarius (NTS)/dorsal motor nucleus of vagus (DMV) complex of the medulla oblongata by in situ hybridization histochemistry. In control saline-treated rats, weak VGF mRNA signals were only rarely detected in neurons of the NTS and none were observed in those in the DMV. After 12 h of cysteamine administration (450 mg/kg, s.c.), the time at which duodenal ulcer was detected in all cases, heavily labeled VGF mRNA-expressing neurons appeared in the NTS and DMV. By quantitative analysis on macroautoradiogram, the VGF mRNA signals of the NTS/DMV complex in cysteamine-treated rats were twice as much as those in saline-treated rats. In situ hybridization histochemistry combined with the use of the retrograde neuronal tracer cholera toxin-B subunit revealed that the induced VGF mRNA-expressing neurons of the DMV projected directly to the stomach. The present results suggest that ulceration accompanies the induction of VGF mRNA in neurons of vagal afferent and efferent areas of the brainstem.