Neurotrophic Effects On Mature Skeletal Muscle

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Degree Type


Degree Name

Doctor of Philosophy


Evidence indicates that the trophic influences of motor nerves on skeletal muscle are mediated both by the release of neurotransmitter (which induces contracile activity) and by secretion of a special trophic substance. Other investigators have shown that extracts of peripheral nerves exert trophic influences on uninnervated muscle cells in vitro. This study was undertaken to determine whether trophic properties of nerve extract are demonstrable in vivo.;Denervated rats' extensor digitorum longus muscles were injected intramuscularly (once or twice daily) with extract of rats' sciatic nerves. After 1 to 14 days, injected muscles and appropriate control muscles were assessed for atrophy (wet weight, total protein, and cross-sectional areas of types IIA and IIB fibres in sections stained for ATPase), activity of acetylcholinesterase or number of acetylcholine receptors (binding of ('125)I-(alpha)-bungarotoxin).;Results indicated that the nerve extract had trophic effects on atrophy of denervated msucles in vivo. The effects were dose-dependent and affected the various types of fibre differently. At optimal concentration, injections of extract completely prevented that component of denervation atrophy not due to inactivity (determined by comparison with immobilized muscles). Loss of trophic influence was responsible for about 40% of the decreases in weight, protein and areas of IIB fibres, but only about 5% of the diminution of IIA fibres, in denervated muscles.;Injections of nerve extract did not reduce the loss of biochemically determined acetylcholinesterase in muscles denervated for 1 week.;Denervated muscles bound considerably more (alpha)-bungarotoxin than innervated controls. Injections of nerve extract did not prevent the increase in acetylcholine receptors, and even produced a greater increase in muscles denervated for 1 day.;Therefore, injection of substances extracted from peripheral nerves is able in vivo to ameliorate some of the consequences of denervation of a skeletal muscle.

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