Cooperative roles of BDNF expression in neurons and schwann cells are modulated by exercise to facilitate nerve regeneration

Document Type

Article

Publication Date

2012

Abstract

After peripheral nerve injury, neurotrophins play a key role in the regeneration of damaged axons that can be augmented by exercise, although the distinct roles played by neurons and Schwann cells are unclear. In this study, we evaluated the requirement for the neurotrophin, brain-derived neurotrophic factor (BDNF), in neurons and Schwann cells for the regeneration of peripheral axons after injury. Common fibular or tibial nerves in thy-1-YFP-H mice were cut bilaterally and repaired using a graft of the same nerve from transgenic mice lacking BDNF in Schwann cells (BDNF -/-) or wild-type mice (WT). Two weeks postrepair, axonal regeneration into BDNF -/-grafts was markedly less thanWTgrafts, emphasizing the importance of Schwann cell BDNF. Nerve regeneration was enhanced by treadmill training posttransection, regardless of the BDNF content of the nerve graft. We further tested the hypothesis that traininginduced increases in BDNF in neurons allow regenerating axons to overcome a lack of BDNF expression in cells in the pathway through which they regenerate. Nerves in mice lacking BDNF in YFP + neurons (SLICK) were cut and repaired with BDNF -/- and WT nerves. SLICK axons lacking BDNF did not regenerate into grafts lacking Schwann cell BDNF. Treadmill training could not rescue the regeneration into BDNF -/- grafts if the neurons also lacked BDNF. Both Schwann cell- and neuron-derived BDNF are thus important for axon regeneration in cut peripheral nerves.

Publication Title

Journal of Neuroscience

Volume

32

Issue

14

First Page

5002

Last Page

5009

Comments

This article was published in Journal of Neuroscience, Volume 32, Issue 14, Pages 5002-5009.

The published version is available at http://dx.doi.org/10.1523/JNEUROSCI.1411-11.2012.

Copyright © 2012 the authors.

This document is currently not available here.

COinS