أعرض في EDS

Activation of Akt/FKHR in the medulla oblongata contributes to spontaneous respiratory recovery after incomplete spinal cord injury in adult rats

التفاصيل البيبلوغرافية
العنوان: Activation of Akt/FKHR in the medulla oblongata contributes to spontaneous respiratory recovery after incomplete spinal cord injury in adult rats
المؤلفون: Patrick Gauthier, Marie-Solenne Felix, Fannie Darlot, Françoise Muscatelli, Anne Kastner, Valéry Matarazzo, Sylvian Bauer
المساهمون: Areva Le Creusot, Groupe AREVA, Institut de Biologie du Développement de Marseille (IBDM), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Physiologie et physiopathologie du système nerveux somato-moteur et neurovégétatif (PPSN), Institut National de la Recherche Agronomique (INRA)-Aix Marseille Université (AMU), Bayer Cropscience, Centre de recherche en neurobiologie - neurophysiologie de Marseille (CRN2M), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Aix Marseille Université (AMU)-Collège de France (CdF)-Centre National de la Recherche Scientifique (CNRS), Aix Marseille Université (AMU)-Institut National de la Recherche Agronomique (INRA)
المصدر: Neurobiology of Disease
Neurobiology of Disease, 2014, 69, pp.93-107. ⟨10.1016/j.nbd.2014.05.022⟩
Neurobiology of Disease, Elsevier, 2014, 69, pp.93-107. ⟨10.1016/j.nbd.2014.05.022⟩
Neurobiology of Disease, Vol 69, Iss, Pp 93-107 (2014)
بيانات النشر: HAL CCSD, 2014.
سنة النشر: 2014
مصطلحات موضوعية: Time Factors, Plasticity, [SDV]Life Sciences [q-bio], Diaphragm, Nerve Tissue Proteins, Functional Laterality, lcsh:RC321-571, Rats, Sprague-Dawley, Phosphatidylinositol 3-Kinases, Cervical hemisection, Medicine, Animals, Respiratory system, Protein kinase B, Spinal cord injury, lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry, PI3K/AKT/mTOR pathway, Medulla, Spinal Cord Injuries, ComputingMilieux_MISCELLANEOUS, Phosphoinositide-3 Kinase Inhibitors, Motor Neurons, Medulla Oblongata, Neuronal Plasticity, business.industry, Akt/PKB signaling pathway, Respiration, Forkhead Transcription Factors, Recovery of Function, FKHR, medicine.disease, P-Akt, Oncogene Protein v-akt, Phrenic Nerve, Disease Models, Animal, Neurology, FOXO1A, Medulla oblongata, Cervical Vertebrae, Female, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Brainstem, business, Neuroscience, Signal Transduction
الوصف: International audience; After incomplete spinal cord injury (SCI), patients and animals may ă exhibit some spontaneous functional recovery which can be partly ă attributed to remodeling of injured neural circuitry. This post-lesion ă plasticity implies spinal remodeling but increasing evidences suggest ă that supraspinal structures contribute also to the functional recovery. ă Here we tested the hypothesis that partial SCI may activate ă cell-signaling pathway(s) at the supraspinal level and that this ă molecular response may contribute to spontaneous recovery. With this ă aim, we used a rat model of partial cervical hemisection which injures ă the bulbospinal respiratory tract originating from the medulla oblongata ă of the brainstem but leads to a time-dependent spontaneous functional ă recovery of the paralyzed hemidiaphragm. We first demonstrate that after ă SCI the PI3K/Akt signaling pathway is activated in the medulla oblongata ă of the brainstem, resulting in an inactivation of its pro-apoptotic ă downstream target, forkhead transcription factor (FKHR/FOXO1A). ă Retrograde labeling of medullary premotoneurons including respiratory ă ones which project to phrenic motoneurons reveals an increased FKHR ă phosphorylation in their cell bodies together with an unchanged cell ă number. Medulla infusion of the PI3K inhibitor, LY294002, prevents the ă SCI-induced Akt and FKHR phosphorylations and activates one of its ă death-promoting downstream targets, Fas ligand. Quantitative EMG ă analyses of diaphragmatic contractility demonstrate that the inhibition ă of medulla PI3K/Akt signaling prevents spontaneous respiratory recovery ă normally observed after partial cervical SCI. Such inhibition does not ă however affect either baseline contractile frequency or the ventilatory ă reactivity under acute respiratory challenge. Together, these findings ă provide novel evidence of supraspinal cellular contribution to the ă spontaneous respiratory recovery after partial SCI. (C) 2014 Elsevier ă Inc All rights reserved.
اللغة: English
تدمد: 0969-9961
1095-953X
URL الوصول: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::762e0950df9f04d65925ca36df17b130
https://hal.science/hal-03436939
حقوق: OPEN
رقم الأكسشن: edsair.doi.dedup.....762e0950df9f04d65925ca36df17b130
قاعدة البيانات: OpenAIRE
الوصف
تدمد:09699961
1095953X