Neuromuscular blockade increases motoneurone survival during normal cell death in the chick embryo.

Abstract

NATURALLY occurring neuronal cell death is a quantitatively significant event in many developing systems1–5; however, the determinants responsible for some neurones surviving while an equal or even greater number degenerate are still unknown. Neurones which undergo spontaneous degeneration have axons in the appropriate peripheral area6,7, and it is generally believed that those neurones which die do so because they are losers in a competition for a limited number of ‘targets’1,8, or a limited amount of ‘trophic substance’9,10. This study was undertaken in an attempt to better understand the parameters which define a ‘target’ and the factors involved in the survival and degeneration of motoneurones in the lateral motor column of the lumbar spinal cord of the chick. Normally by embryonic day 6 a peak of approximately 22,000–24,000 motoneurones is found in each lateral motor column whereas by day 9 there are 13,500 and by day 12, and continuing through hatching, each lateral motor column consists of 11,000–11,500 motoneurones (unpublished data, also see refs 3, 11). We report here that contrary to what might be expected12, embryos treated during the period of normal cell death with botulinum toxin (BTX) or curare contain about 5,500 more motoneurones (a 50% increase) in each lateral motor column after the period of cell death is over. Treatment with the irreversible nicotinic receptor blocker α-cobratoxin (CT, from Naja naja siamensis) also produced an increase in motoneurone survival; however, no studies were carried out with this agent beyond day 10.