MOTONEURONS DESTINED TO DIE ARE RESCUED BY BLOCKING N-METHYL-D-ASPARTATE RECEPTORS BY MK-801

Motoneurons to soleus muscle die if their axons are injured at birth.7,16 We tested the possibility that their death may be caused by toxic effects of excitatory transmitters such as glutamate. Animals that had their sciatic nerves crushed at birth were treated either with a blocker of the N-methyl-D-aspartate receptor, dizocilpine maleate (MK-801), or saline. The number of surviving soleus motoneurons and motor units was assessed 60-90 days later. Treatment of rats with MK-801 rescued a large proportion of injured motoneurons destined to die. Moreover, the weight loss of soleus muscles seen after nerve injury at birth was reduced in animals treated with MK-801. These results suggest that motoneurons axotomized at birth are unable to withstand the excitotoxic effects of glutamate and die.8 Blocking glutamate receptors in conditions where motoneuron loss occurs could be an effective way of rescuing them.