Exercise-Induced Activation of NMDA Receptor Promotes Motor Unit Development and Survival in a Type 2 Spinal Muscular Atrophy Model Mouse
| Autor: | Hung Li, Philippe Lopes, Sylvie Lécolle, Séverine Deforges, Carmen Cifuentes-Diaz, Bruno Della Gaspera, Frédéric Charbonnier, Christophe Chanoine, Clément Grondard, Claude Pariset, Olivier Biondi |
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| Přispěvatelé: | Laboratoire de Neurobiologie des Réseaux Sensorimoteurs (LNRS), Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5), Université Paris Diderot - Paris 7 (UP7) - Université Paris Descartes - Paris 5 (UPD5) |
| Rok vydání: | 2008 |
| Předmět: |
MESH: Mice
Transgenic Cell Survival [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology Mice Transgenic Physical exercise MESH: Physical Conditioning Animal Spinal Muscular Atrophies of Childhood Biology MESH: Mice Knockout Receptors N-Methyl-D-Aspartate Neuroprotection Mice 03 medical and health sciences 0302 clinical medicine Physical Conditioning Animal medicine Animals Humans MESH: Animals Muscle Skeletal MESH: Mice 030304 developmental biology Mice Knockout Motor Neurons MESH: Receptors N-Methyl-D-Aspartate MESH: Muscle Skeletal 0303 health sciences MESH: Humans General Neuroscience [SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology Articles Spinal muscular atrophy Motor neuron Spinal cord medicine.disease SMA Motor unit Disease Models Animal medicine.anatomical_structure MESH: Cell Survival nervous system NMDA receptor MESH: Disease Models Animal Neuroscience MESH: Motor Neurons 030217 neurology & neurosurgery MESH: Spinal Muscular Atrophies of Childhood |
| Zdroj: | Journal of Neuroscience Journal of Neuroscience, Society for Neuroscience, 2008, 28 (4), pp.953-62. ⟨10.1523/JNEUROSCI.3237-07.2008⟩ Journal of Neuroscience, Society for Neuroscience, 2008, 28 (4), pp.953-62. <10.1523/JNEUROSCI.3237-07.2008> |
| ISSN: | 1529-2401 0270-6474 |
| DOI: | 10.1523/jneurosci.3237-07.2008 |
| Popis: | Spinal muscular atrophy (SMA) is an inborn neuromuscular disorder caused by low levels of survival motor neuron protein, and for which no efficient therapy exists. Here, we show that the slower rate of postnatal motor-unit maturation observed in type 2 SMA-like mice is correlated with the motor neuron death. Physical exercise delays motor neuron death and leads to an increase in the postnatal maturation rate of the motor-units. Furthermore, exercise is capable of specifically enhancing the expression of the gene encoding the major activating subunit of the NMDA receptor in motor neurons, namely the NR2A subunit, which is dramatically downregulated in the spinal cord of type 2 SMA-like mice. Accordingly, inhibiting NMDA-receptor activity abolishes the exercise-induced effects on muscle development, motor neuron protection and life span gain. Thus, restoring NMDA-receptor function could be a promising therapeutic approach to SMA treatment. |
| Databáze: | OpenAIRE |
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