c-Fos in enteric nerves after extrinsic denervation of guinea pig ileum

Background. Gastrointestinal function is controlled partly by an interactio n between extrinsic (sympathetic, parasympathetic, sensory) and intrinsic ( enteric) nerves. However, normal gut function occurs in the absence of extr insic innervation as enteric nerves adapt to the loss of extrinsic nerves f rom the gut wall. Expression of the proto-oncogene product, c-Fos, is a sig nal for activity-dependent changes in gene expression and immunocytochemica l detection of c-Fos is used as a marker for changes in neuronal activity. The purpose of this study was to determine if enteric neurons in guinea pig ileum respond to loss of extrinsic innervation by expressing c-Fos protein . Materials and methods. Fos protein was localized using immunohistochemical methods and an antiserum raised against synthetic Fos. Segments of ileum we re extrinsically denervated by crushing the mesenteric nerves in anesthetiz ed animals or by treating animals with 6-hydroxydopamine (6-OH-DA) or capsa icin to destroy sympathetic and extrinsic sensory nerves, respectively. Results. One week after surgical extrinsic denervation of loops of ileum, 1 2 +/- I nuclei/submucosal ganglion and 114 +/- 6 nuclei/myenteric ganglion contained Fos immunoreactivity (ir). These values were greater (P < 0.05) t han those from unoperated segments from the same animals (4 +/- I Fos-ir nu clei/submucosal ganglion and 13 +/- 4 Fos-ir nuclei/myenteric ganglion) or from sham-operated segments. Significantly more nuclei contained Fos-ir at 4, 7, 10, and 24 weeks after denervation. Finally, capsaicin or B-OH-DA tre atment increased the number of Fos-ir nuclei in enteric ganglia. Conclusions. These data suggest that Fos expression may be part of the adap tation of enteric nerves to extrinsic denervation. (C) 1999 Academic Press.