Transient muscle paralysis in neonatal rats renders motoneurons susceptible to N-methyl-D-aspartate-induced neurotoxicity.
Paralysis of the soleus muscle in newborn rats causes a large proportion of motoneurons to die by 10 weeks of age. However, all of these neurons are still present at three to four weeks of age. We have previously shown that although nerve injury at five days does not result in any motoneuron death, it does render these neurons susceptible to the toxic effects of the glutamate agonist N-methyl-D-aspartate. Using retrograde labelling of soleus motoneurons, in this study we show that an increased susceptibility to glutamate also plays a role in the eventual death of those motoneurons which survive for three weeks after interruption of neuromuscular transmission at birth but die by 10 weeks. Treatment with dizocilpine maleate an antagonist of the N-methyl-D-aspartate receptor increased the survival of motoneurons to alpha-bungarotoxin-treated soleus muscles. By 10 weeks of age the size of motoneurons to alpha-bungarotoxin-treated soleus muscles is smaller than that of controls, but after treatment with dizocilpine maleate the sizes of motoneurons to control and treated muscles are similar. Moreover, only 55 +/- 2.7% of motoneurons to the soleus muscle paralysed at birth with alpha-bungarotoxin survive for three weeks after a single injection of N-methyl-D-aspartate at 12 days of age. This motoneuron death is due to the application of N-methyl-D-aspartate since treatment with alpha-bungarotoxin alone causes no loss of neurons at this age.(ABSTRACT TRUNCATED AT 250 WORDS)
Greensmith
L
L
Department of Anatomy and Developmental Biology, University College, London, U.K.
Sanusi
J
J
Mentis
G Z
GZ
Vrbová
G
G
D000818:Animals; D016291:Dizocilpine Maleate / Q000494:pharmacology; D006801:Humans; D007231:Infant, Newborn; D009046:Motor Neurons / Q000187:drug effects* / Q000502:physiology; D018482:Muscle, Skeletal / Q000187:drug effects / Q000502:physiology; D009132:Muscles / Q000187:drug effects*; D016202:N-Methylaspartate / Q000494:pharmacology*; D010243:Paralysis / Q000145:classification*; D051381:Rats; D017208:Rats, Wistar; D013116:Spinal Cord / Q000187:drug effects / Q000502:physiology
D016202:N-Methylaspartate; D016291:Dizocilpine Maleate