The regulation of motoneuron survival and differentiation by putative muscle-derived neurotrophic agents: neuromuscular activity and innervation.

The chronic blockade of neuromuscular activity is known to promote the survival of developing motoneurons in vivo in the chick, mouse and rat embryo. Increased survival in this situation may reflect an activity-dependent mechanism for the regulation of trophic factor production by target cells. To test this notion, we have examined motoneuron survival in vivo and choline acetyltransferase (ChAT) development in vitro following treatment of chick embryos and rat spinal cord cultures with partially purified skeletal muscle extracts derived from normally active, chronically paralyzed and aneural embryos, and from denervated postnatal chickens. Extracts from active and paralyzed chick embryos were equally effective in promoting motoneuron survival and ChAT activity. Aneural embryonic muscle extracts were slightly less effective in promoting motoneurons survival in vivo, but were not significantly different from control extracts in the in vitro ChAT assay. Denervated postnatal muscle extracts, however, were more effective in enhancing both motoneuron survival and ChAT activity. These data indicate that: (1) the promotion of motoneuron survival in vivo by activity blockade may not be mediated by an up-regulation of trophic factor synthesis in target cells; (2) postnatal innervation may regulate the production of putative muscle-derived neurotrophic factors; and (3) the synthesis or availability of trophic agents may be regulated differently in embryonic and postnatal muscle.