Exercise-induced activation of NMDA receptor promotes motor unit development and survival in a type 2 spinal muscular atrophy model mouse.

J Neurosci. 2008 Jan 23;28(4):953-62. Biondi O, Grondard C, Lécolle S, Deforges S, Pariset C, Lopes P, Cifuentes-Diaz C, Li H, della Gaspera B, Chanoine C, Charbonnier F. “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”. The authors have previously shown that running enhanced motor neuron function and increased life span in type 2 SMA-like mice. In the present study, the authors investigated whether there is a direct relationship between maturation state of a motor neurons and resistance to neuronal cell death. Further they report the signaling pathway by which exercise provides neuroprotection in SMA-like mice. They report their findings after performing a series of experiments in a knock-out transgenic SMA-like mice. The authors report that exercise leads to a delay in motor-neuron death, which is independent of the rate of postnatal motor-unit maturation. In the spinal cord motor neurons of neonatal SMA-like mice the authors observed a defective expression of NR2A subunit. In addition, the expression of NR2A subunit is enhanced in the trained SMA-like mice suggesting that this could contribute to NMDA-receptor activation in type 2 SMA-like mice. Further, the authors inhibited NMDA-receptor activity to show that exercise-induced benefits in the trained type 2 SMA-like mice were suppressed. The authors conclude that restoring the function of NMDA receptor could be a potential treatment for SMA.- Madhan