Regeneration of sensory but not motor axons following visceral nerve injury.
Following peripheral nerve injury, restoration of function may occur via the regeneration of injured axons or compensatory sprouting of spared axons. Injury to visceral nerves that control urogenital organs is a common consequence of pelvic surgery, however their capacity to reinnervate organs is poorly understood. To determine if and how sensory and motor connections to the bladder are re-established, a novel surgical model of visceral nerve injury was performed unilaterally in adult male Wistar rats. Bladder-projecting motor and sensory neurons in pelvic ganglia and lumbosacral dorsal root ganglia, respectively, were identified and characterised by retrograde tracing and immunofluorescence. Application of tracers ipsi- and contralateral to injury distinguished the projection pathways of new connections in the bladder. In naive animals, the majority of sensory and motor neurons project ipsilaterally to the bladder, while ~20 % project contralaterally and ~5 % bilaterally. Injured axons of motor neurons were unable to regenerate by 4weeks after transection. In contrast, by this time many injured sensory neurons regrew axons to reform a substantial plexus within the detrusor and suburothelial tissues. These regeneration responses were also indicated by upregulation of activating transcription factor-3 (ATF-3), which was sustained in motor neurons but transient in sensory bladder-projecting neurons. Axotomy had little or no effect on the survival of bladder-projecting sensory and motor neurons. We also found evidence that uninjured motor and sensory neurons develop additional projections to the denervated bladder tissue and return connectivity, likely by undergoing compensatory growth. In conclusion, our results show that visceral sensory and motor neurons have a different capacity to regenerate axons following axotomy, however in both components of the circuit uninjured bladder neurons spontaneously grow new axon collaterals to replace the lost terminal field within the organ. For a full functional recovery, understanding the environmental and cellular mechanisms that reduce the ability of pelvic ganglion cells to undergo axonal regeneration is needed.
Department of Anatomy and Neuroscience, The University of Melbourne, Victoria 3010, Australia. Electronic address: sophie.payne@unimelb.edu.au.
Sophie C
SC
Payne
Department of Anatomy and Neuroscience, The University of Melbourne, Victoria 3010, Australia.
Philip J
PJ
Belleville
Department of Anatomy and Neuroscience, The University of Melbourne, Victoria 3010, Australia.
Janet R
JR
Keast
D051700:Activating Transcription Factor 3 / Q000096:biosynthesis; D000818:Animals; D001369:Axons / Q000473:pathology*; D019771:Axotomy; D002452:Cell Count; D002470:Cell Survival; D008297:Male; D009046:Motor Neurons / Q000473:pathology*; D009416:Nerve Regeneration; D009434:Neural Pathways / Q000473:pathology; D059348:Peripheral Nerve Injuries / Q000473:pathology*; D051381:Rats; D017208:Rats, Wistar; D011984:Sensory Receptor Cells / Q000473:pathology*; D001743:Urinary Bladder / Q000294:innervation / Q000473:pathology
D051700:Activating Transcription Factor 3; C497108:Atf3 protein, rat
Axotomy; Bladder innervation; Collateral sprouting; Inferior hypogastric plexus; Nerve regeneration; Pelvic ganglia; Pelvic surgery