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C W Modert

Publications and source records attributed to C W Modert.

6 recordsLinked to original sources
PubMed1987

Orthograde and retrograde axonal transport of dopamine-beta-hydroxylase in ileal mesenteric nerves of rats with chronic streptozotocin diabetes.

Rats with chronic streptozotocin-induced diabetes develop a neuropathy involving the ileal mesenteric nerves. Distal portions of these postganglionic sympathetic axons develop markedly dilated, dopamine-beta-hydroxylase (DBH)-containing dystrophic swellings. These findings led us to develop a quantitative method to examine orthograde and retrograde axonal transport of DBH in ileal mesenteric nerves. Surprisingly, no significant alteration in orthograde or retrograde axonal transport of DBH was identified.

Animals↗
PubMed1984

Orthograde, retrograde, and turnaround axonal transport of dopamine-beta-hydroxylase: response to axonal injury.

Reversal of the direction (turnaround) of orthograde axonal transport of dopamine-beta-hydroxylase (DBH) activity was studied at a ligature placed on rat sciatic nerve. DBH was allowed to accumulate at a ligature in vivo for selected intervals, at which time a second ligature was placed proximal to the first and turnaround transport measured just distal to the second tie after incubation in vivo or in vitro. Orthograde accumulation of DBH activity proximal to a ligature peaked at 2 days, and then rapidly decreased as a result of turnaround transport and injury-induced reduction of orthograde transport. Destruction of postganglionic sympathetic axon terminals in vivo with 6 hydroxydopamine resulted in a decrease in orthograde transport similar to that seen after axotomy and turnaround at or proximal to the site of chemical injury. Turnaround transport of DBH in vitro was blocked by incubation in the cold and in the presence of NaCN and vinblastine. Orthograde transport of DBH appeared to reverse direction within a few millimeters of a ligature.

Afferent Pathways↗
PubMed1983

Neuroaxonal dystrophy in the autonomic ganglia of aged rats.

Distinctive axonal abnormalities in selected sympathetic ganglia of male and female Sprague-Dawley and male Fischer 344 rats have been characterized as a function of increasing age. Dilated intraganglionic axons contained a variety of unusual subcellular organelles, including large numbers of compact or loosely aggregated tubulovesicular profiles, layered membranous loops, and collections of normal and degenerating organelles, identical to those described in clinical and experimental neuroaxonal dystrophy. Although occasional dystrophic axons were encountered free within the ganglionic neuropil, the majority were intimately associated with the surface of major dendrites or perikarya of principal sympathetic neurons and presumably represent terminal preganglionic axons. However, neither synaptic vesicles in dystrophic axons nor the association of dystrophic axons with post-synaptic densities were demonstrated. Dystrophic axons were infrequent within the prevertebral superior mesenteric and celiac ganglia before one year of age, but increased substantially in numbers thereafter. Similar findings expressed as lesions per mm2 were approximately tenfold less frequent in the paravertebral superior cervical ganglia of the same animals.

Aging↗
PubMed1983

Retrograde axonal transport of intravenously administered 125I-nerve growth factor in rats with streptozotocin-induced diabetes.

We have previously demonstrated a reproducible axonopathy, involving but not confined to sympathetic neurons, which involves selectively the mesenteric nerves of chronically diabetic rats. We describe a series of experiments aimed at correlating changes in the retrograde transport of 125I-nerve growth factor (125I-NGF) with development of the lesions. 125I-NGF was injected systemically and the time course of accumulation compared in superior cervical ganglion (SCG) and superior mesenteric ganglion (SMG). 125I-NGF accumulated in the SCG with a sharp peak at 12 h, whereas in the SMG, accumulation reached a plateau, remaining at relatively constant amounts for 8 h before decreasing. There was a marked decrease in the accumulation of 125I-NGF (averaging 44% in 11 separate experiments) in the SMG at early times (approximately 12 h). These decreases were seen in animals diabetic for times ranging from 2 days to 10 mo. In contrast, no consistent decrease was observed in the SCG. The time course of 125I-NGF accumulation was unaltered in the SCG of diabetic rats but was clearly retarded in the SMG of diabetic animals. Morphometric examination of the SMG of diabetic animals and controls showed little or no atrophy or neuron loss due to diabetes. We conclude that decreases in the retrograde transport of NGF occur selectively in those ganglia (SMG) serving the alimentary tract in which mesenteric nerves develop distal axonopathy, but not in ganglia whose nerves do not ultimately develop such lesions (SCG). The decreases in retrograde transport precede the development of morphologic lesions in this system. These results are consistent with the suggestion that impairment of axonal transport may play a role in the development of axonopathy.

Animals↗
PubMed1983

Experimental diabetic autonomic neuropathy characterization in streptozotocin-diabetic Sprague-Dawley rats.

Rats with chronic streptozotocin-induced diabetes develop enlargement of the alimentary tract, loss of fecal consistency, and autonomic neuropathy involving the extrinsic innervation of the ileum. In this study we have continued the characterization of the unmyelinated axonopathy involving the ileal mesenteric nerves of outbred Sprague-Dawley rats diabetic for 1.5 to 10 months using ultrastructural methods. Axonopathy in the alimentary tract of chronically diabetic rats is characterized by modest to marked dilation of axons by distinctive subcellular organelles identical with those described in experimental and clinical axonal dystrophies. Lesions are infrequent 1.5 and 3 months after induction of diabetes, increasing rapidly in numbers thereafter. Axonal lesions are reproducibly encountered in the ileum, cecum, and rectum but not in the proximal jejunum of chronically diabetic rats. Sectioning of mesenteric nerves along their longitudinal axes demonstrates the focal and in some instances apparent terminal nature of the axonal dilation. Disappearance of dystrophic axons distal (peripheral) to mesenteric crush injury confirms the origin of the axons extrinsic to the gut wall. Only rare examples of dystrophic diabetic axonopathy were detected within the wall of the ileum, presumably representing involvement of terminal axonal segments within the intrinsic ganglia. Examination of the mesenteric nerves of 18- and 30-month-old control rats failed to demonstrate dystrophic axonopathy, providing evidence that diabetic axonopathy does not represent premature development of an aging change in mesenteric nerves. Examination of the autonomic innervation of various other tissues including spleen, bladder, vas deferens, and iris, as well as the phrenic, sciatic, vagus, and tail nerves of 4- to 12-month diabetic animals, failed to demonstrate reproducible axonopathy comparable to that involving the alimentary tract of the same animals. The paravascular fascicles of ileal mesenteric nerves of 6- to 7-month diabetic and age-matched control rats were examined by morphometric methods and failed to demonstrate significant loss of axons or an appreciable shift in mean fiber diameter.

Aging↗