Remodeling of B-50 (GAP-43)- and NSE-immunoreactive mucosal nerves in the intestines of rats infected with Nippostrongylus brasiliensis
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Intestinal mucosal mast cells (IMMCs) are closely apposed to nerves, which is consistent with other evidence suggesting that mast cells are innervated. Recent studies have indicated that coordinated changes in mast cell and nerve densities occur in the gut mucosa, during progressive fibrosis, but there is a lack of experimental evidence to support remodeling of intestinal nerve fibers as part of a disease process. Infection of rats with the nematode Nippostrongylus brasiliensis (Nb) results in an initial loss of stainable IMMCs, during an acute inflammatory phase, with subsequent mast cell hyperplasia. Accordingly, we employed the Nb model to look for structural neuroplasticity of intestinal mucosal nerves during inflammation. Immunocytochemical labeling of neurofilament subunits was very low in the jejunal mucosa of all animals, whereas neuron-specific enolase (NSE)-immunoreactive nerves were relatively abundant in control animals. The number of NSE-immunoreactive profiles increased approximately 2.5-fold by day 10 (d10) postinfection (p less than 0.01) and returned to near control values by d14. Immunoreactivity for B-50/GAP-43 was more extensive, labeling more than four times the number of nerves per villus, compared with NSE (p less than 0.0001). B-50 immunoreactivity decreased minimally (ca. 20%) by d7 postinfection, and then increased through control values between d10 and d21, to 30% greater than controls at d49 (p less than 0.05). Subclassification of the B-50-immunoreactive nerves according to cross-sectional area revealed a greater than twofold increase in the proportions of large fibers at d7 and d10. Subsequently, the proportions of small nerves were increased compared with controls. The fiber size changes were found to correlate with mast cell densities (r = -0.72 for large and r = 0.76 for small nerves). At d10, dilated B-50- and NSE-immunoreactive nerves predominated, and extraneuronal NSE was noted. Electron microscopy revealed that this was due to axonal dilation and degeneration. These data provide evidence for plasticity of intestinal mucosal nerve fibers during inflammation. This includes early degenerative and later regenerative phases that appear to correlate with mast cell densities. The phenotype of mucosal nerves in control animals suggests ongoing modeling of these fibers.
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