In vivo NMDA receptor activation accelerates motor unit maturation, protects spinal motor neurons, and enhances SMN2 gene expression in severe spinal muscular atrophy mice.

J Neurosci. 2010 Aug 25;30(34):11288-99. Biondi O, Branchu J, Sanchez G, Lancelin C, Deforges S, Lopes P, Pariset C, Lécolle S, Côté J, Chanoine C, Charbonnier F. “Spinal muscular atrophy (SMA), a lethal neurodegenerative disease that occurs in childhood, is caused by the misexpression of the survival of motor neuron (SMN) protein in motor neurons”. In the present study, the authors evaluated whether activation of NMDA receptor in a type 2 SMA mouse affects SMN expression and motor neuron survival in SMA spinal cord. The authors reported the level at which NMDA receptor gets activated could provide beneficial or detrimental effects. At adequate level it could accelerate motor unit maturation, prevention of the spinal motor neurons from apoptosis and modification of SMN2 expression. At higher levels of activation, it could provide opposite effects. Further activation of NMDA receptor lead to reactivation of downstream signaling pathway enhancing SMN expression suggesting that activation of NMDA receptor at adequate levels could be used in enhancing SMN expression and reducing motor neuron death in SMA spinal cord. - Madhan