Ultrastructural and immunohistochemical characterization of autonomic neuropathy in genetically diabetic Chinese hamsters.

Selected portions of the prevertebral and paravertebral sympathetic and vagal parasympathetic nervous systems have been examined in the genetically diabetic Chinese hamster, an experimental animal model of diabetic gastrointestinal disease. The prevertebral sympathetic superior mesenteric/celiac ganglia, which provide much of the sympathetic innervation of the alimentary tract, developed large numbers of markedly dilated axons, many of which had the ultrastructural features of neuroaxonal dystrophy. Dystrophic axons, many involving presynaptic axonal elements, were increased in frequency in the prevertebral superior mesenteric/celiac ganglia, but not in the paravertebral superior cervical sympathetic ganglia, of chronically diabetic hamsters in comparison with age-matched controls. Dystrophic axons contained substance P- and gastrin-releasing peptide (gastrin-releasing peptide/bombesin)-like staining but were not labeled by antisera directed against vasoactive intestinal peptide, dynorphin-B, somatostatin, leu- and met-enkephalin and neuropeptide tyrosine. Substance P and gastrin-releasing peptide/bombesin containing subpopulations of presynaptic elements in prevertebral sympathetic ganglia are thought to participate in local reflex control of bowel motility and lesions preferentially involving these elements may contribute to bowel dysfunction. Immunohistologic techniques failed to demonstrate dystrophic axons in the superior cervical ganglia. Although morphometric studies failed to show significant axon loss in the abdominal vagus of chronically diabetic Chinese hamsters, evidence of markedly diminished numbers of axons comprising each Schwann cell unit and regenerative collections of Schwann cell processes devoid of axons are consistent with the participation of parasympathetic elements in the pathogenesis of alimentary dysfunction in this model system. These results suggest that selective subpopulations of neuropeptide containing axons are vulnerable to the diabetic condition and that these abnormalities may lead to physiologic dysfunction.