title: Sex differences in the effectiveness of treadmill training in enhancing axon regeneration in injured peripheral nerves.
abstract: Exercise in the form of daily treadmill training results in significant enhancement of axon regeneration following peripheral nerve injury. Because androgens are also linked to enhanced axon regeneration, we wanted to investigate whether sex differences in the effect of treadmill training might exist. The common fibular nerves of thy-1-YFP-H mice were cut and repaired with a graft of the same nerve from a strain-matched wild-type donor mouse. Animals were treated with one of two daily treadmill training paradigms: slow continuous walking for 1 h or four higher intensity intervals of 2 min duration separated by 5-min rest periods. Training was begun on the third day following nerve injury and continued 5 days per week for 2 weeks. Effects on regeneration were evaluated by measuring regenerating axon profile lengths in optical sections through the repair sites and grafts at the end of the training period. No sex differences were found in untrained control mice. Continuous training resulted in significant enhancement of axon regeneration only in males. No effect was found in females or in castrated males. Interval training was effective in enhancing axon regeneration only in females and not in intact males or castrated males. Untrained females treated with the aromatase inhibitor, anastrozole, had significant enhancement of axon regeneration without increasing serum testosterone levels. Two different mechanisms exist to promote axon regeneration in a sex-dependent manner. In males treadmill training uses testicular androgens. In females, a different cellular mechanism for the effect of treadmill training must exist.
authors.affiliation: Department of Cell Biology, Emory University, Atlanta, Georgia, USA.
authors.forename: Kylene
authors.initials: K
authors.lastname: Wood
authors.forename: Jennifer C
authors.initials: JC
authors.lastname: Wilhelm
authors.forename: Manning J
authors.initials: MJ
authors.lastname: Sabatier
authors.forename: Kevin
authors.initials: K
authors.lastname: Liu
authors.forename: Jingsheng
authors.initials: J
authors.lastname: Gu
authors.forename: Arthur W
authors.initials: AW
authors.lastname: English
mesh_terms: D000818:Animals; D001369:Axons / Q000502:physiology* / Q000648:ultrastructure; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D009416:Nerve Regeneration / Q000187:drug effects / Q000502:physiology*; D059348:Peripheral Nerve Injuries / Q000503:physiopathology* / Q000534:rehabilitation* / Q000601:surgery; D010805:Physical Conditioning, Animal / Q000379:methods / Q000502:physiology*; D020813:Receptor, trkB / Q000378:metabolism; D012727:Sex Characteristics; D018800:Thy-1 Antigens / Q000235:genetics
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D018800:Thy-1 Antigens; D020813:Receptor, trkB