Conditioning lesions enhance growth state only in sensory neurons lacking calcitonin gene-related peptide and isolectin B4-binding

• Published in: Neuroscience Vol. 166; no. 1; pp. 107 - 121
• Main Authors: Kalous, A, Keast, J.R
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Ltd 10.03.2010; Elsevier
• Subjects: Animals; axonal regeneration; axotomy; Biological and medical sciences; Calcitonin Gene-Related Peptide - genetics; Calcitonin Gene-Related Peptide - metabolism; Cells, Cultured; Denervation; Fundamental and applied biological sciences. Psychology; Ganglia, Spinal - cytology; Ganglia, Spinal - drug effects; Ganglia, Spinal - injuries; Ganglia, Spinal - metabolism; Growth Cones - drug effects; Growth Cones - metabolism; Growth Cones - ultrastructure; Immunohistochemistry; Male; Mice; Mice, Inbred C57BL; mouse; Nerve Growth Factor - metabolism; Nerve Growth Factor - pharmacology; Nerve Regeneration - drug effects; Nerve Regeneration - physiology; Neurology; neurotrophic factor; nociceptor; Peripheral Nerve Injuries; Peripheral Nerves - cytology; Peripheral Nerves - drug effects; Peripheral Nerves - metabolism; Plant Lectins - metabolism; Receptor, trkA - drug effects; Receptor, trkA - metabolism; Recovery of Function - physiology; Sciatic Neuropathy - genetics; Sciatic Neuropathy - metabolism; Sciatic Neuropathy - physiopathology; Sensory Receptor Cells - cytology; Sensory Receptor Cells - drug effects; Sensory Receptor Cells - metabolism; Signal Transduction - drug effects; Signal Transduction - physiology; Staining and Labeling; Vertebrates: nervous system and sense organs; nociceptor; phosphate-buffered saline; extracellular signal-related protein kinase; glial cell line-derived neurotrophic factor; mouse; growth-associated proteins; nerve growth factor; GAP-43; PI 3-kinase; phophatidylinositol 3-kinase; PBS; ATF-3; axonal regeneration; tropomyosin-related kinase A; neurotrophic factor; STAT3; CCI; chronic constriction injury; calcitonin gene-related peptide; signal transducer and activator of transcription 3; axotomy; NGF; activating transcription factor-3; Bandeiraea simplicifolia I-isolectin B4; TrkA; GDNF; dorsal root ganglion; DRG; IB4; CGRP; Erk; Growth; Rodentia; Calcitonin gene related peptide; Neuropeptide; Neurotrophic factor; Regeneration; Vertebrata; Axotomy; Nociceptor; Mammalia; Mouse; Animal; Sensory neuron; Conditioning; Lesion
• ISSN: 0306-4522; 1873-7544
• DOI: 10.1016/j.neuroscience.2009.12.019

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.