Exercise-induced activation of NMDA receptor promotes motor unit development and survival in a type 2 spinal muscular atrophy model mouse.
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.
Biondi
Olivier
O
Laboratoire de Neurobiologie des Réseaux Sensorimoteurs, Centre Universitaire des Saints-Pères, Université Paris Descartes, Unité Mixte de Recherche 7060, Centre National de la Recherche Scientifique, F-75270 Paris Cedex 06, France.
Grondard
Clément
C
Lécolle
Sylvie
S
Deforges
Séverine
S
Pariset
Claude
C
Lopes
Philippe
P
Cifuentes-Diaz
Carmen
C
Li
Hung
H
della Gaspera
Bruno
B
Chanoine
Christophe
C
Charbonnier
Frédéric
F
D000818:Animals; D002470:Cell Survival / Q000235:genetics; D004195:Disease Models, Animal; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009046:Motor Neurons / Q000378:metabolism* / Q000473:pathology; D018482:Muscle, Skeletal / Q000254:growth & development / Q000378:metabolism / Q000473:pathology; D010805:Physical Conditioning, Animal / Q000502:physiology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D014897:Spinal Muscular Atrophies of Childhood / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology
C120997:NR2A NMDA receptor; D016194:Receptors, N-Methyl-D-Aspartate