Enhancement of Peripheral Nerve Regeneration due to Treadmill Training and Electrical Stimulation is Dependent on Androgen Receptor Signaling Open Access

Thompson, Nicholas (2013)

Permanent URL: https://etd.library.emory.edu/concern/etds/474299274?locale=en
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Abstract

Moderate exercise in the form of treadmill training and brief electrical nerve stimulation (ES) both enhance axon regeneration after peripheral nerve injury. Androgens were suspected to be involved in the enhancement of axon regeneration due to treadmill training because of a sex difference previously identified, in which different regimens of exercise lead to dissimilar results of axon regeneration between male and female mice (Wood et al., 2012). We treated mice with the androgen receptor blocker, flutamide, prior to either exercise or ES, to evaluate the role of androgen receptor signaling in these methods of enhancing axon regeneration. The common fibular (CF) and tibial (TIB) nerves of thy-1-YFP-H mice, in which axons in peripheral nerves are marked by yellow fluorescent protein (YFP), were transected and repaired using CF and TIB nerve grafts harvested from non-fluorescent donor mice. Silastic capsules filled with flutamide were implanted subcutaneously to release the drug continuously. Exercised mice were treadmill trained five days/week for two weeks, starting on the third day post transection. For ES, the sciatic nerve was stimulated continuously for one hour prior to nerve transection. After two weeks, lengths of YFP+ axon profiles were measured from harvested nerves. Both exercise and ES enhanced axon regeneration, but this enhancement was blocked completely by flutamide treatments. Signaling through androgen receptors is necessary for the enhancing effects of treadmill exercise or ES on axon regeneration in cut peripheral nerves.

Table of Contents

Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
Materials and Methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4
Results . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9
Discussion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15

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