title: Endogenous modulation of TrkB signaling by treadmill exercise after peripheral nerve injury.
abstract: 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.
authors.affiliation: Institute of Neurosciences, Department of Cell Biology, Physiology and Immunology, Universitat Autònoma de Barcelona, and Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Bellaterra, Spain.
authors.forename: Ariadna
authors.initials: A
authors.lastname: Arbat-Plana
authors.affiliation: Institute of Neurosciences, Department of Cell Biology, Physiology and Immunology, Universitat Autònoma de Barcelona, and Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Bellaterra, Spain.
authors.forename: Stefano
authors.initials: S
authors.lastname: Cobianchi
authors.affiliation: Institute of Neurosciences, Department of Cell Biology, Physiology and Immunology, Universitat Autònoma de Barcelona, and Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Bellaterra, Spain.
authors.forename: Mireia
authors.initials: M
authors.lastname: Herrando-Grabulosa
authors.affiliation: Institute of Neurosciences, Department of Cell Biology, Physiology and Immunology, Universitat Autònoma de Barcelona, and Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Bellaterra, Spain.
authors.forename: Xavier
authors.initials: X
authors.lastname: Navarro
authors.affiliation: Institute of Neurosciences, Department of Cell Biology, Physiology and Immunology, Universitat Autònoma de Barcelona, and Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Bellaterra, Spain. Electronic address: esther.udina@uab.cat.
authors.forename: Esther
authors.initials: E
authors.lastname: Udina
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism; D008159:Lumbar Vertebrae; D009046:Motor Neurons / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D009457:Neuroglia / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D059225:Nociception / Q000502:physiology; D017288:Pain Threshold / Q000502:physiology; D059348:Peripheral Nerve Injuries / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D020813:Receptor, trkB / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D020812:Receptor, trkC / Q000378:metabolism; D012420:Running / Q000502:physiology*; D012584:Sciatic Nerve / Q000293:injuries; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D013569:Synapses / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D050598:Vesicular Glutamate Transport Protein 1 / Q000378:metabolism
chemical_list: D019208:Brain-Derived Neurotrophic Factor; C493466:Slc17a7 protein, rat; D050598:Vesicular Glutamate Transport Protein 1; D018698:Glutamic Acid; D020813:Receptor, trkB; D020812:Receptor, trkC; D051057:Proto-Oncogene Proteins c-akt
keywords: BDNF; TrkB; motoneurons; nerve injury; synaptic stripping; treadmill running