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Journal of Neuroscience, Vol 11, 2829-2837, Copyright © 1991 by Society for Neuroscience
Regulation of putative muscle-derived neurotrophic factors by muscle activity and innervation: in vivo and in vitro studies
LJ Houenou, JL McManaman, D Prevette and RW Oppenheim
Department of Neurobiology and Anatomy, Bowman Gray School of Medicine, Wake Forest University, Winston-Salem, North Carolina 27103.
The normal embryonic development of spinal cord motoneurons (MNs) involves
the proliferation of precursor cells followed by the degeneration of
approximately 50% of postmitotic MNs during the period when nerve-muscle
connections are being established. The death of MNs in vivo can be
ameliorated by activity blockade and by treatment with muscle extracts.
Muscle activity and innervation have been suggested to regulate the
availability of putative muscle-derived neurotrophic agent(s), and MNs are
thought to compete for limited amounts of these trophic agents during
normal development. Thus, activity and innervation are thought to regulate
MN survival by modulating trophic factor availability. We have tested this
notion by examining MN survival in vivo and ChAT development in spinal cord
neurons in vitro following treatments with partially purified muscle
extracts from normally active, paralyzed (genetically or
pharmacologically), aneural, denervated, slow tonic, and fast-twitch
muscles from embryonic and postnatal animals. Extracts from active and
chronically inactive embryonic avian and mouse muscles were found to be
equally effective in promoting the in vivo survival of MNs in the chick
embryo. Similarly, extracts from fast-twitch and slow tonic postnatal avian
muscles did not differ in their ability to promote both MN survival in vivo
and ChAT activity in vitro. Although aneural and control embryonic muscle
extract had similar effects on ChAT development in vitro, aneural muscle
extract contained somewhat less MN survival-promoting activity when tested
in vivo. By contrast, denervated postnatal muscle extract was more
effective in promoting both MN survival in vivo and ChAT activity in vitro
than age-matched control muscle extract.(ABSTRACT TRUNCATED AT 250 WORDS)
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