Abstract
Study design:
Morphological and Stereological assessment of the dorsal root transitional zone (DRTZ) following complete crush injury, using light microscopy (LM) and transmission electron microscopy (TEM).
Objectives:
To assess the effect of exogenous neurotrophin-3 (NT-3) on the response of glial cells and axons to dorsal root damage.
Setting:
Department of Anatomy, University College Cork, Ireland and Department of Physiology, UMDS, University of London, UK.
Methods:
Cervical roots (C6-8) from rats which had undergone dorsal root crush axotomy 1 week earlier, in the presence (n=3) and absence (n=3) of NT-3, were processed for LM and TEM.
Results:
Unmyelinated axon number and size was greater in the DRTZ proximal (Central Nervous System; CNS) and distal (Peripheral Nervous System; PNS) compartments of NT-3-treated tissue. NT-3 was associated with a reduced astrocytic response, an increase in the proportion of oligodendrocytic tissue and a possible inhibition or delay of microglial activation. Disrupted-myelin volume in the DRTZ PNS and CNS compartments of treated tissue was lower, than in control tissue. In the PNS compartment, NT-3 treatment increased phagocyte and blood vessel numbers. It decreased myelinating activity, as sheath thickness was significantly lower and may also account for the noted lower Schwann cell and organelle volume in the test group.
Conclusions:
Our observations suggest that NT-3 interacts with non-neuronal tissue to facilitate the regenerative effort of damaged axons. This may be as a consequence of a direct action or indirectly mediated by modulation of non-neuronal responses to injury.
Similar content being viewed by others
Log in or create a free account to read this content
Gain free access to this article, as well as selected content from this journal and more on nature.com
or
References
Aldskogius H, Kozlova EN . Strategies for repair of the deafferented spinal cord. Brain Res Brain Res Rev 2002; 40: 301–308.
Rossignol S, Schwab M, Schwartz M, Fehlings MG . Spinal cord injury: time to move? J Neurosci 2007; 27: 11782–11792.
Hannila SS, Filbin MT . The role of cyclic AMP signaling in promoting axonal regeneration after spinal cord injury. Exp Neurol 2008; 209: 321–332.
Fraher JP . The transitional zone and CNS regeneration. J Anat 1999; 194 (Part 2): 161–182.
Ramón y Cajal S . Degeneration and Regeneration in the Nervous System. Translated and edited by Raoul M May. Oxford University Press: London, 1928.
Schulte-Herbruggen O, Braun A, Rochlitzer S, Jockers-Scherubl MC, Hellweg R . Neurotrophic factors—a tool for therapeutic strategies in neurological, neuropsychiatric and neuroimmunological diseases? Curr Med Chem 2007; 14: 2318–2329.
Blochl A, Blochl R . A cell-biological model of p75NTR signaling. J Neurochem 2007; 102: 289–305.
Gundersen HJ, Jensen EB . The efficiency of systematic sampling in stereology and its prediction. J Microsc 1987; 147 (Part 3): 229–263.
Ramer MS, Bishop T, Dockery P, Mobarak MS, O’Leary D, Fraher JP et al. Neurotrophin-3-mediated regeneration and recovery of proprioception following dorsal rhizotomy. Mol Cell Neurosci 2002; 19: 239–249.
Ramer MS, McMahon SB, Priestley JV . Axon regeneration across the dorsal root entry zone. Prog Brain Res 2001; 132: 621–639.
Ramer MS, Priestley JV, McMahon SB . Functional regeneration of sensory axons into the adult spinal cord. Nature 2000; 403: 312–316.
Ramer LM, McPhail LT, Borisoff JF, Soril LJ, Kaan TK, Lee JH et al. Endogenous TrkB ligands suppress functional mechanosensory plasticity in the deafferented spinal cord. J Neurosci 2007; 27: 5812–5822.
McPhail LT, Borisoff JF, Tsang B, Hwi LP, Kwiecien JM, Ramer MS . Protracted myelin clearance hinders central primary afferent regeneration following dorsal rhizotomy and delayed neurotrophin-3 treatment. Neurosci Lett 2007; 411: 206–211.
Shuman SL, Bresnahan JC, Beattie MS . Apoptosis of microglia and oligodendrocytes after spinal cord contusion in rats. J Neurosci Res 1997; 50: 798–808.
Scholz J, Woolf CJ . The neuropathic pain triad: neurons, immune cells and glia. Nat Neurosci 2007; 10: 1361–1368.
Tzeng SF, Huang HY, Lee TI, Jwo JK . Inhibition of lipopolysaccharide-induced microglial activation by preexposure to neurotrophin-3. J Neurosci Res 2005; 81: 666–676.
Kraemer R, Hempstead BL . Neurotrophins: novel mediators of angiogenesis. Front Biosci 2003; 8: s1181–s1186.
Zakharenko S, Popov S . Dynamics of axonal microtubules regulate the topology of new membrane insertion into the growing neurites. J Cell Biol 1998; 143: 1077–1086.
Chan JR, Cosgaya JM, Wu YJ, Shooter EM . Neurotrophins are key mediators of the myelination program in the peripheral nervous system. Proc Natl Acad Sci USA 2001; 98: 14661–14668.
Yamauchi J, Chan JR, Shooter EM . Neurotrophins regulate Schwann cell migration by activating divergent signaling pathways dependent on Rho GTPases. Proc Natl Acad Sci USA 2004; 101: 8774–8779.
Acknowledgements
These studies were carried out as part of the European Union Biomed II programme (Grant number: BMH4-CT97-2586) and the HEA PRTL1 programme (Grant number 51243526).
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Hanna-Mitchell, A., O'Leary, D., Mobarak, M. et al. The impact of neurotrophin-3 on the dorsal root transitional zone following injury. Spinal Cord 46, 804–810 (2008). https://doi.org/10.1038/sc.2008.57
Received:
Revised:
Accepted:
Published:
Issue date:
DOI: https://doi.org/10.1038/sc.2008.57
Keywords
This article is cited by
-
NT-3 Combined with TGF-β Signaling Pathway Enhance the Repair of Spinal Cord Injury by Inhibiting Glial Scar Formation and Promoting Axonal Regeneration
Molecular Biotechnology (2023)
-
The effect of OTK18 upregulation in U937 cells on neuronal survival
In Vitro Cellular & Developmental Biology - Animal (2009)
