Blockade of N-methyl-D-aspartate receptors by MK-801 (dizocilpine maleate) rescues motoneurones in developing rats.
In rats following nerve injury at birth a large proportion of motoneurones to the soleus muscle dies. Blocking of N-methyl-D-aspartate (NMDA) receptors by MK-801 (dizocilpine maleate) for 12 days after nerve injury at birth leads to rescue of a proportion of motoneurones destined to die. Retrograde labelling of soleus motoneurones shows that 6-8 weeks after crushing the sciatic nerve in one hindlimb, only 10.9 +/- 2.3% of the motoneurones have survived. In animals treated with an NMDA receptor blocker MK-801 (2 mg/kg i.p., from birth to 12 days old) 50.6 +/- 3.8% of soleus motoneurones survived. This neuroprotective effect of MK-801 was dose dependant, since after treatment with lower doses (0.5 mg/kg; 1 mg/kg) fewer motoneurones survived (13.7% and 34.5%, respectively). To assess the effect of treatment with MK-801 on survival of alpha-motoneurones only, the number of soleus motor units was established physiologically. After nerve injury alone only 4.2 +/- 1.2 of the 29-30 soleus motor units were present, while in animals treated with MK-801 (2 mg/kg) 14 +/- 1.5 motor units were identified. The neuroprotective effect of MK-801 was not confined to soleus motoneurones but was also apparent on motoneurones to the extensor digitorum longus (EDL). In untreated EDL muscles of the 40 motor units only 5.5 +/- 1.7 motor units survived neonatal nerve injury and this number increased to 18 +/- 2.6 after treatment with MK-801. The neuroprotective effect of MK-801 was apparent regardless of whether the nerve lesion was carried out close to or far from the soleus muscle.
Greensmith
L
L
Department of Anatomy and Developmental Biology, University College London, UK.
Mentis
G Z
GZ
Vrbová
G
G
D000818:Animals; D000831:Animals, Newborn; D001369:Axons / Q000502:physiology; D001522:Behavior, Animal / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D009046:Motor Neurons / Q000187:drug effects*; D024510:Muscle Development; D018482:Muscle, Skeletal / Q000166:cytology / Q000254:growth & development / Q000294:innervation*; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*
D016194:Receptors, N-Methyl-D-Aspartate; D016291:Dizocilpine Maleate