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Journal of Neuroscience, Vol 11, 3809-3821, Copyright © 1991 by Society for Neuroscience
Remodeling of B-50 (GAP-43)- and NSE-immunoreactive mucosal nerves in the intestines of rats infected with Nippostrongylus brasiliensis
RH Stead, U Kosecka-Janiszewska, AB Oestreicher, MF Dixon and J Bienenstock
Department of Pathology, McMaster University, Hamilton, Ontario, Canada.
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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