title: Long-term regeneration of abdominal vagus: efferents fail while afferents succeed.
abstract: Vagal afferents regenerate, by 18 weeks after subdiaphragmatic transection, to reinnervate the gut and to differentiate into the two types of terminals normally found in the smooth muscle wall of the gastrointestinal (GI) tract (Phillips et al. [2000] J Comp Neurol. 421:325-346). Regeneration, however, is neither complete nor entirely accurate by 18 weeks. Moreover, the capacity of the vagal efferents to reinnervate the GI tract under comparable conditions has not been evaluated. Therefore, to determine whether a more extended postaxotomy survival interval would (1). result in more extensive reinnervation of smooth muscle, (2). facilitate correction of the inaccuracies of the regenerated axons and terminals, and (3). yield motor as well as sensory reinnervation of GI targets, Sprague-Dawley rats received either complete subdiaphragmatic vagotomies (n = 18) or sham surgeries (n = 12). Physiological endpoints that might normalize as vagal elements regenerated, including body weight, daily food intake, size of first daily meal, and metabolic efficiency, were monitored. At 45 weeks after the vagotomies, the animals were randomly assigned to afferent (wheat germ agglutinin-horseradish peroxidase) or efferent (cholera toxin subunit B-horseradish peroxidase) mapping conditions, and labeled axons and terminals in the stomach and first 8 cm of the small intestine were inventoried in whole-mounts. Afferent regeneration was more extensive at 45 weeks than previously observed at 18 weeks after surgery; however, the amount of GI innervation was still not comparable to the intact pattern of the sham rats. Furthermore, abnormal patterns of sensory organization occurred throughout the reinnervated field, with small bundles of axons forming complex tangles and some individual axons terminating in ectopic locations. The presence of growth cone profiles suggested that vagal reorganization was ongoing even 45 weeks after surgery. In contrast to this relatively extensive, albeit incomplete, sensory reinnervation of the gut, motor fibers had failed to reinnervate the GI tract. Thus, dramatic differences exist in the regenerative capacities of the sensory and motor arms of the vagus under the same surgical and maintenance conditions. Furthermore, the functional measures of disordered energy regulation did not normalize over the 45 weeks during which afferent but not efferent innervation was restored.
authors.affiliation: Purdue University, Department of Psychological Sciences, West Lafayette, Indiana 47907, USA. rphillip@psych.perdue.edu
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Phillips
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Baronowsky
authors.forename: Terry L
authors.initials: TL
authors.lastname: Powley
mesh_terms: D000818:Animals; D004064:Digestive System / Q000294:innervation*; D004435:Eating / Q000502:physiology; D008297:Male; D009416:Nerve Regeneration / Q000502:physiology*; D009473:Neuronal Plasticity / Q000502:physiology*; D009475:Neurons, Afferent / Q000166:cytology / Q000473:pathology / Q000502:physiology*; D009476:Neurons, Efferent / Q000166:cytology / Q000473:pathology / Q000502:physiology*; D009620:Nodose Ganglion / Q000166:cytology / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014628:Vagotomy; D014630:Vagus Nerve / Q000166:cytology / Q000473:pathology / Q000502:physiology*; D017833:Visceral Afferents / Q000166:cytology / Q000473:pathology / Q000502:physiology