Induction of transmitter release at the neuromuscular junction prevents motoneuron death after axotomy in neonatal rats.
Motoneurons to rat hindleg muscles die after neonatal nerve injury. Here we show that increasing transmitter release of motor nerve terminals by treatment with 4-aminopyridine, prior to nerve injury at three days, reduces the extent of motoneuron death. Retrograde labelling of soleus motoneurons was carried out in 10-week-old animals that had their sciatic nerve crushed on one side when they were three days old. Only 20% (+/- 4.2 S.E.M.) of the motoneurons survived the nerve injury. A group of animals similarly injured at three days had their calf muscles treated with 4-aminopyridine at birth, prior to nerve injury. In these animals a significantly higher percentage (51 +/- 6.6% S.E.M.) of soleus motoneurons survived. In order to assess the proportion of surviving alpha-motoneurons only, the number of motor units in both the soleus and extensor digitorum longus muscles was established by following the stepwise increments of twitch tension in response to increasing intensity of stimulation of the respective motor nerve. After nerve injury at three days only 18% (+/- 4.1% S.E.M.) of motor units to soleus and 28.5% (+/- 4.9% S.E.M.) to extensor digitorum longus survived and were able to reinnervate their respective muscles. If the nerve injury was preceded by local application of 4-aminopyridine, then the number of motor units present in the reinnervated muscles was significantly greater, so that in soleus 52.7% (+/- 5.4% S.E.M.) and in extensor digitorum longus 52.1% (+/- 2.4% S.E.M.) of motor units were present. This increase of motoneuron survival was reflected in a smaller weight loss and in a better restoration of force production by the pretreated as compared to untreated muscles on reinnervation after nerve injury. It is suggested that enhancing transmitter release from nerve endings in neonatal animals induces the motoneuron to become more resistant to nerve injury.
Greensmith
L
L
Department of Anatomy and Developmental Biology, University College London, U.K.
Dick
J
J
Emanuel
A O
AO
Vrbová
G
G
D015761:4-Aminopyridine / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D001369:Axons / Q000502:physiology*; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D005260:Female; D008297:Male; D009046:Motor Neurons / Q000187:drug effects / Q000502:physiology*; D009119:Muscle Contraction / Q000502:physiology; D009121:Muscle Denervation; D018482:Muscle, Skeletal / Q000187:drug effects / Q000294:innervation / Q000502:physiology; D009409:Nerve Crush; D009416:Nerve Regeneration / Q000502:physiology; D009469:Neuromuscular Junction / Q000187:drug effects / Q000378:metabolism*; D018377:Neurotransmitter Agents / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012584:Sciatic Nerve / Q000187:drug effects / Q000378:metabolism / Q000502:physiology
D018377:Neurotransmitter Agents; D015761:4-Aminopyridine