Voluntary exercise increases axonal regeneration from sensory neurons

doi:10.1073/pnas.0401443101

Voluntary exercise increases axonal regeneration from sensory neurons

Departments of ^*Neurosurgery and ^¶Physiological Science, and ^∥Brain Injury Research Center, University of California, Los Angeles, CA 90095; and ^§Nemours Biomedical Research, A. I. duPont Hospital for Children, Wilmington, DE 19803

Edited by Eric M. Shooter, Stanford University School of Medicine, Stanford, CA (received for review March 1, 2004)

Abstract

Recent advances in understanding the role of neurotrophins on activity-dependent plasticity have provided insight into how behavior can affect specific aspects of neuronal biology. We present evidence that voluntary exercise can prime adult dorsal root ganglion neurons for increased axonal regeneration through a neurotrophin-dependent mechanism. Dorsal root ganglion neurons showed an increase in neurite outgrowth when cultured from animals that had undergone 3 or 7 days of exercise compared with sedentary animals. Neurite length over 18–22 h in culture correlated directly with the distance that animals ran. The exercise-conditioned animals also showed enhanced regrowth of axons after an in vivo nerve crush injury. Sensory ganglia from the 3- and 7-day-exercised animals contained higher brain-derived neurotrophic factor, neurotrophin 3, synapsin I, and GAP43 mRNA levels than those from sedentary animals. Consistent with the rise in brain-derived neurotrophic factor and neurotrophin 3 during exercise, the increased growth potential of the exercise-conditioned animals required activation of the neurotrophin signaling in vivo during the exercise period but did not require new mRNA synthesis in culture.

Footnotes

↵ ** To whom correspondence should be addressed at: A. I. duPont Hospital for Children, 1600 Rockland Road, Wilmington, DE 19803. E-mail: twiss{at}medsci.udel.edu.
↵ † R.M. and J.-Q.Z. contributed equally to this work.
↵ ‡ Present address: Department of Pharmacological Sciences, Center for Neuropharmacology, University of Milan, 20133 Milan, Italy.
This paper was submitted directly (Track II) to the PNAS office.
Abbreviations: BDNF, brain-derived neurotrophic factor; NT3, neurotrophin 3; DRG, dorsal root ganglion; CytC, cytochrome c; DRB, 5,6-dichlorobenzimidazole 1-β-d-ribofuranoside.