title: Involvement of Cdc2 in axonal regeneration enhanced by exercise training in rats.
abstract: OBJECTIVE
  Physical activity can improve sensorimotor recovery after peripheral nerve injury. We examined the effects of treadmill training (TMT) on axonal regeneration in the injured sciatic nerve of the rat and further investigated cellular and molecular events that underlie enhanced axonal regrowth by training.
  
  
  METHODS
  After crush injury of the sciatic nerves, rats were randomly assigned into either TMT or sedentary groups. Three to 14 d after injury, changes in protein levels in the regenerating nerve were analyzed by Western blotting and immunofluorescence staining. Axonal regeneration was assessed by anterograde and retrograde tracing techniques. The animals' functional recovery was determined by the sciatic functional index.
  
  
  RESULTS
  We identified enhanced axonal regrowth in the distal stump of the sciatic nerve 7-14 d after injury in the rats with TMT. Cell division cycle 2 (Cdc2) mRNA and protein levels were highly increased in the injured sciatic nerves 3 and 7 d after injury, and decreased to basal levels 14 d later. Daily TMT accelerated distal shift of Cdc2 mRNA and protein induced in the regenerating nerves, and Cdc2 kinase activity was similarly increased in the distal stump by TMT. Cdc2 protein induced by TMT was mainly colocalized with Schwann cell marker S100beta protein, and correlated with axial distribution pattern of bromodeoxyuridine-labeled proliferating cell population in the regenerating nerve. We further demonstrate that axonal regeneration and motor function recovery after injury, both of which were promoted by TMT, were greatly suppressed by in vivo administration of Cdc2 inhibitor roscovitine.
  
  
  CONCLUSIONS
  The present data suggest that Cdc2 kinase activated in the regenerating sciatic nerve may play an important role in TMT-mediated enhancement of axonal regeneration.
authors.affiliation: Department of Oriental Medicine, Daejeon University, Daejeon, Korea.
authors.forename: Tae Beom
authors.initials: TB
authors.lastname: Seo
authors.forename: In Sun
authors.initials: IS
authors.lastname: Han
authors.forename: Jin-Hwan
authors.initials: JH
authors.lastname: Yoon
authors.forename: Kwon-Eui
authors.initials: KE
authors.lastname: Hong
authors.forename: Sung-Jin
authors.initials: SJ
authors.lastname: Yoon
authors.forename: Uk
authors.initials: U
authors.lastname: Namgung
mesh_terms: D000818:Animals; D001369:Axons; D016203:CDC2 Protein Kinase / Q000032:analysis*; D005080:Exercise Test; D009409:Nerve Crush; D009416:Nerve Regeneration / Q000502:physiology*; D010805:Physical Conditioning, Animal / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012584:Sciatic Nerve / Q000293:injuries
chemical_list: D016203:CDC2 Protein Kinase