Journal
EXPERIMENTAL NEUROLOGY
Volume 223, Issue 1, Pages 153-165Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.expneurol.2009.08.025
Keywords
Femoral transection; Axon reinnervation; Recombinant adenovirus; Nerve growth factor; Axon guidance; Axon targeting; Triple retrograde tracing
Categories
Funding
- NINDS NIH HHS [R01 NS040592-06, R01 NS040592-07, R01NS40592, R01 NS040592, R01 NS040592-08] Funding Source: Medline
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Even though peripheral nerves regenerate well, axons are often misrouted and reinnervate inappropriate distal pathways post-injury. Misrouting most likely occurs at branch points where regenerating axons make choices. Here, we show that the accuracy of sensory axon reinnervation is enhanced by overexpression of the guidance molecule nerve growth factor (NGF) distal to the bifurcation. We used the femoral nerve as a model, which contains both sensory and motor axons that intermingle in the parent trunk and distally segregate into the saphenous (SB) and motor branches (MB). Transection of the parent trunk resulted in misrouting of axon reinnervation to SB and MB. To enhance sensory axon targeting, recombinant adenovirus encoding NGF was injected along the SB close to the bifurcation 1 week post-injury. The accuracy of axon reinnervation was assessed by retrograde tracing at 3 or 8 weeks after nerve injury. NGF overexpression significantly increased the accuracy of SB axon reinnervation to the appropriate nerve branch, in a manner independent of enhancing axon regeneration. This novel finding provides in vivo evidence that gradient expression of neurotrophin can be used to enhance targeting of distal peripheral pathways to increase axon regeneration into the appropriate nerve branch. (C) 2009 Elsevier Inc. All rights reserved.
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