Involvement of Cdc2 in Axonal Regeneration Enhanced by Exercise Training in Rats

Seo, Tae Beom; Han, In Sun; Yoon, Jin-Hwan; Hong, Kihyon; Yoon, SungJin; Namgung, Uk

doi:10.1249/01.mss.0000227311.00976.68

Cited by 56 publications

(65 citation statements)

References 26 publications

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“…Marqueste et al (2004) found that treadmill training after common fibular nerve transection and repair results in better mechano-and metabosensitive afferent recovery in rats (Marqueste, et al, 2004). A more recent report showed a positive effect of treadmill training on axon regeneration in rats after sciatic nerve crush (Seo, et al, 2006). However, this is the first study to provide direct evidence of a positive effect of post-injury exercise training on axon regeneration after peripheral nerve transection.…”

Section: Discussionmentioning

confidence: 86%

“…Intensity was manipulated by altering treadmill speed. Continuous training has been used more extensively in animal exercise studies and has been applied in previous studies of exercise after peripheral nerve injury (Marqueste, et al, 2004, Seo, et al, 2006. However, the preferred approach to patterned running for rodents is brief intervals of high-intensity running interspersed with periods of rest (De Bono, et al, 2006).…”

Section: Discussionmentioning

confidence: 99%

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Treadmill training promotes axon regeneration in injured peripheral nerves

Sabatier

Redmon

Schwartz

et al. 2008

Experimental Neurology

150

153

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Physical activity after spinal cord injury promotes improvements in motor function, but its effects following peripheral nerve injury are less clear. Although axons in peripheral nerves are known to regenerate better than those in the CNS, methods of accelerating regeneration are needed due to the slow overall rate of growth. Therefore we studied the effect of two weeks of treadmill locomotion on the growth of regenerating axons in peripheral nerves following injury. The common fibular nerves of thy-1-YFP-H mice, in which a subset of axons in peripheral nerves express yellow fluorescent protein (YFP), were cut and repaired with allografts from non-fluorescent littermates, and then harvested two weeks later. Mice were divided into groups of low-intensity continuous training (CT, 60 minutes), low-intensity interval training (IT; one group, 10 reps, 20 minutes total), and high-intensity IT (three groups, 2, 4, and 10 reps). One repetition consisted of two minutes of running and five minutes of rest. Sixty minutes of CT resulted in the highest exercise volume, whereas two reps of IT resulted in the lowest volume of exercise. The lengths of regenerating YFP + axons were measured in images of longitudinal optical sections of nerves. Axon profiles were significantly longer than control in all exercise groups except the low-intensity IT group. In the CT group and the high-intensity IT groups that trained with four or 10 repetitions axons were more than twice as long as unexercised controls. The number of intervals did not impact axon elongation. Axon sprouting was enhanced in IT groups but not the CT group. Thus exercise, even in very small quantities, increases axon elongation in injured peripheral nerves whereas continuous exercise resulting in higher volume (total steps) may have no net impact on axon sprouting.

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Section: Discussionmentioning

confidence: 86%

Section: Discussionmentioning

confidence: 99%

Treadmill training promotes axon regeneration in injured peripheral nerves

Sabatier

Redmon

Schwartz

et al. 2008

Experimental Neurology

150

153

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“…Moderate exercise in the form of treadmill training has been shown to enhance axon regeneration following peripheral nerve injury in mice (English et al 2009;Sabatier et al 2008) and rats (Asensio-Pinilla et al 2009;Ilha et al 2008;Seo et al 2006;Udina et al 2011), but its full effects on functional recovery are not known. We hypothesized that moderate exercise in the form of daily treadmill training during the first 2 wk following transection and repair of the rat sciatic nerve would lead to improved functional recovery.…”

Section: Discussionmentioning

confidence: 99%

“…In studies from our laboratory in mice (Sabatier et al 2008), exercise in the form of moderate daily treadmill training results in a marked enhancement of axon regeneration in cut nerves. Others have reported a variety of different training paradigms in different injury models (crush or transection) in rats that result in enhanced axon regeneration (Asensio-Pinilla et al 2009;Ilha et al 2008;Seo et al 2006;Udina et al 2011). We have used a combination of transgenic and knockout mice to show that the enhancement of axon regeneration produced by this moderate exercise is the result of an autocrine neurotrophin stimulation of regeneration of injured axons (Wilhelm et al 2012).…”

mentioning

confidence: 99%

Effects of treadmill training on functional recovery following peripheral nerve injury in rats

Boeltz

Ireland

Mathis

et al. 2013

Journal of Neurophysiology

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“…Given that Cdc2 activation mediates cell proliferation and (Seo et al, 2006). Here we explored Cdc2 function in Schwann cells associated with nerve regeneration, and found that Cdc2 expression was induced in Schwann cells and promoted Schwann cell migration, which is functionally related to the nerve regeneration process.…”

Section: Introductionmentioning

confidence: 98%

Cdc2-mediated Schwann cell migration during peripheral nerve regeneration

Han

Seo

Kim

et al. 2007

Journal of Cell Science

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Schwann cell migration facilitates peripheral nerve regeneration after injury. We have recently found increased activation of Cdc2 kinase in regenerating sciatic nerves. Here we show that Cdc2 phosphorylation of caldesmon regulates Schwann cell migration and nerve regeneration. A robust but transient increase in Cdc2 expression was found in cultured Schwann cells prepared from the sciatic nerve in rats that had undergone crush injury for 7 days. These `injury-preconditioned' Schwann cells exhibited enhanced migration compared with non-preconditioned control cells and treatment with the cdk inhibitor roscovitine prevented cell migration. After transduction with recombinant Cdc2 DNA adenoviral vectors, Schwann cells were implanted into sciatic nerves; those expressing wild-type Cdc2 migrated further in the distal direction than those expressing dominant-negative Cdc2. We identified caldesmon as a downstream substrate of Cdc2 in Schwann cells and its phosphorylation by Cdc2 changed its subcellular localization. Overexpression of dominant-negative caldesmon significantly counteracted the migration effect caused by Cdc2. Finally, neurite outgrowth of cultured DRG sensory neurons, facilitated by co-culture with injury-preconditioned Schwann cells, was suppressed by roscovitine treatment. The results indicate that activation of the Cdc2-caldesmon pathway is necessary for Schwann cell migration and suggest a role for this pathway in peripheral axonal growth.

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Involvement of Cdc2 in Axonal Regeneration Enhanced by Exercise Training in Rats

Abstract: 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.

Cited by 56 publications

References 26 publications

Treadmill training promotes axon regeneration in injured peripheral nerves

Treadmill training promotes axon regeneration in injured peripheral nerves

Effects of treadmill training on functional recovery following peripheral nerve injury in rats

Cdc2-mediated Schwann cell migration during peripheral nerve regeneration

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