Endogenous modulation of TrkB signaling by treadmill exercise after peripheral nerve injury

Ariadna Arbat-Plana, Stefano Cobianchi, Mireia Herrando-Grabulosa, Xavier Navarro, Esther Udina

Research output: Contribution to journalArticleResearchpeer-review

8 Citations (Scopus)

Abstract

© 2016 IBRO After peripheral nerve injury, transected fibers distal to the lesion are disconnected from the neuronal body. This results in target denervation but also massive stripping of the central synapses of axotomized motoneurons, disrupting spinal circuits. Even when axonal regeneration is successful, the non-specific target reinnervation and the limited rebuilding of spinal circuits impair functional recovery. Therefore, strategies aimed to preserve spinal circuits after nerve lesions may improve the functional outcome. Activity-dependent therapy in the form of early treadmill running reduces synaptic stripping, mainly of excitatory synapses, and the disorganization of perineuronal nets (PNNs) on axotomized motoneurons. The mechanism underlying these effects remains unknown, although the benefits of exercise are often attributed to an increase in the neurotrophin brain-derived neurotrophic factor (BDNF). In this study, tropomyosin-related kinase (TrkB) agonist and antagonist were administered to rats subjected to sciatic nerve injury in order to shed light on the role of BDNF. The maintenance of synapses on axotomized motoneurons induced by treadmill running was partially dependent on TrkB activation. Treatment with the TrkB agonist at a low dose, but not at a high dose, prevented the decrease of excitatory glutamatergic synapses, and both doses increased the density of inhibitory synapses. TrkB inactivation counteracted only some of the positive effects exerted by exercise after nerve injury, such as maintenance of excitatory synapses surrounding motoneurons. Therefore, specific regimes of physical exercise are a better strategy to attenuate the alterations that motoneurons suffer after axotomy than pharmacological modulation of the TrkB pathway.
Original languageEnglish
Pages (from-to)188-200
JournalNeuroscience
Volume340
Issue number6
DOIs
Publication statusPublished - 6 Jan 2017

Keywords

  • BDNF
  • motoneurons
  • nerve injury
  • synaptic stripping
  • treadmill running
  • TrkB

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