title: Conditioning lesions enhance growth state only in sensory neurons lacking calcitonin gene-related peptide and isolectin B4-binding.
abstract: A conditioning lesion improves regeneration of central and peripheral axons of dorsal root ganglion (DRG) neurons after a subsequent injury by enhancing intrinsic growth capacity. This enhanced growth state is also observed in cultured DRG neurons, which support a more sparsely and rapidly elongating mode of growth after a prior conditioning lesion in vivo. Here we examined differences in the capacity or requirements of specific types of sensory neurons for regenerative growth, which has important consequences for development of strategies to improve recovery after injury. We showed that after partial or complete injury of the sciatic nerve in mice, an elongating mode of growth in vitro was activated only in DRG neurons that did not express calcitonin gene-related peptide (CGRP) or bind Bandeiraea simplicifolia I-isolectin B4 (IB4). We also directly examined the response of conditioned sensory neurons to nerve growth factor (NGF), which does not enhance growth in injured peripheral nerves in vivo. We showed that after partial injury, NGF stimulated a highly branched and linearly restricted rather than elongating mode of growth. After complete injury, the function of NGF was impaired, which immunohistochemical studies of DRG indicated was at least partly due to downregulation of the NGF receptor, tropomyosin-related kinase A (TrkA). These results suggest that, regardless of the type of conditioning lesion, each type of DRG neuron has a distinct intrinsic capacity or requirement for the activation of rapidly elongating growth, which does not appear to be influenced by NGF.
authors.affiliation: Pain Management Research Institute and Kolling Institute, University of Sydney at Royal North Shore Hospital, St Leonards, NSW 2065, Australia.
authors.forename: A
authors.initials: A
authors.lastname: Kalous
authors.forename: J R
authors.initials: JR
authors.lastname: Keast
mesh_terms: D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D003714:Denervation; D005727:Ganglia, Spinal / Q000166:cytology / Q000187:drug effects / Q000293:injuries / Q000378:metabolism*; D020439:Growth Cones / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D020932:Nerve Growth Factor / Q000378:metabolism / Q000494:pharmacology; D009416:Nerve Regeneration / Q000187:drug effects / Q000502:physiology*; D059348:Peripheral Nerve Injuries; D010525:Peripheral Nerves / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D037121:Plant Lectins / Q000378:metabolism; D020917:Receptor, trkA / Q000187:drug effects / Q000378:metabolism; D020127:Recovery of Function / Q000502:physiology; D020426:Sciatic Neuropathy / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D011984:Sensory Receptor Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013194:Staining and Labeling
chemical_list: C045475:Griffonia simplicifolia lectins; D037121:Plant Lectins; D020932:Nerve Growth Factor; D020917:Receptor, trkA; D015740:Calcitonin Gene-Related Peptide