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Prevention of natural motoneurone cell death by dibutyryl cyclic GMP


Natural neuronal cell death is a well-described developmental phenomenon common to many nerve centres in a variety of animal species1–8. Neuronal survival has been shown to depend on the presence9–11 and size of the available target tissue12,13 and it has been suggested that neuronal survival is dependent on successful competition for either a limited number of synaptic sites1,14 or a limited amount of trophic factor(s)9,15. In the lateral motor column of the lumbar spinal cord in the chick embryo, the period of axon elongation and innervation of the periphery has been shown to precede that of natural motoneurone cell death16,17. While muscle contractile activity appears to regulate the extent of motoneurone death18, to date the intracellular molecular events that initiate and regulate the developmental process of natural neuronal cell death or, more importantly, neuronal survival are unknown. Our earlier studies suggested that either contact or association between spinal cord processes and muscle cells during neuromuscular junction formation in vivo leads to an increase in cyclic GMP in whole spinal cord19. We now show that treatment of chick embryos with the membrane-permeable cyclic GMP analogue, dibutyryl cyclic GMP during the period of natural motoneurone cell death prevents >58% of natural motoneurone cell death in the lumbar lateral motor column.

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Weill, C., Greene, D. Prevention of natural motoneurone cell death by dibutyryl cyclic GMP. Nature 308, 452–454 (1984).

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