Role of noradrenergic inputs from locus coeruleus on changes induced on axotomized motoneurons by physical exercise

Physical rehabilitation is one of the cornerstones for the treatment of lesions of the nervous system. After peripheral nerve injuries, activity dependent therapies promote trophic support for the paralyzed muscles, enhance axonal growth and also modulate the maladaptive plastic changes induced by t...

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Detalles Bibliográficos
Autores: Arbat-Plana, Ariadna|||0000-0003-0479-8323, Puigdomenech, Maria, Navarro, X. (Xavier)|||0000-0001-9849-902X, Udina i Bonet, Esther|||0000-0003-1954-8562
Tipo de recurso: artículo
Fecha de publicación:2019
País:España
Institución:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:223812
Acceso en línea:https://ddd.uab.cat/record/223812
https://dx.doi.org/urn:doi:10.3389/fncel.2019.00065
Access Level:acceso abierto
Palabra clave:Periferal nerve injury
Spinal circuitry
Physical exercise
Motoneuron
Noradrenaline
Locus coeruleus
Descripción
Sumario:Physical rehabilitation is one of the cornerstones for the treatment of lesions of the nervous system. After peripheral nerve injuries, activity dependent therapies promote trophic support for the paralyzed muscles, enhance axonal growth and also modulate the maladaptive plastic changes induced by the injury at the spinal level. We have previously demonstrated that an intensive protocol of treadmill running (TR) in rats reduces synaptic stripping on axotomized motoneurons, preserves their perineuronal nets (PNN) and attenuates microglia reactivity. However, it is not clear through which mechanisms exercise is exerting these effects. Here we aimed to evaluate if activation of the locus coeruleus (LC), the noradrenergic center in the brain stem, plays a role in these effects. Since LC is strongly activated during stressful situations, as during intensive exercise, we selectively destroyed the LC by administering the neurotoxin DPS-4 before injuring the sciatic nerve of adult rats. Animals without LC had increased microglia reactivity around injured motoneurons. In these animals, an increasing intensity protocol of TR was not able to prevent synaptic stripping on axotomized motoneurons and the reduction in the thickness of their PNN. In contrast, TR was still able to attenuate microglia reactivity in DSP-4 treated animals, thus indicating that the noradrenergic projections are important for some but not all the effects that exercise induces on the spinal cord after peripheral nerve injury. Moreover, animals subjected to treadmill training showed delayed muscle reinnervation, more evident if treated with DSP-4. However, we did not find differences in treated animals regarding the H/M amplitude ratio, which increased during the first stages of regeneration in all injured groups.