Changes in the enzyme histochemistry of skeletal muscle during experimental denervation and reinnervation

Abstract

Histochemical studies were made of the tibialis anterior muscle from rats following crush or section of the sciatic nerve. At intervals varying between 48 hours and 9 months the animals were sacrificed, samples taken and sections stained for the mitochondrial enzymes diphosphopyridine (DPN) and triphosphopyridine (TPN), diaphorase, succinate dehydrogenase and beta hydroxybutyrate dehydrogenase and for the glycolytic enzymes, the DPN-dependent a glycerosphosphate and lactate dehydrogenase. Non-specific acid and alkaline phosphatases, non-specific esterases and phosphorylase activity were also estimated. A loss of glycogenolytic enzymatic activity was demonstrated in all fibers at the end of the first week after denervation. A total loss was seen in the absence of reinnervation. A gradual loss of succinate dehydrogenase activity was found after denervation, indicating that the Krebs cycle is not being used significantly. This, in turn, is related to the decreased energy requirements of denervated muscle. The overall increase of DPN diaphorase suggests that some other metabolic pathway is being used. Non-specific esterase is increased in "red" fibers and more so in "white" fibers. This enzyme is found where lipids and fatty acids are being metabolized. This suggests that the metabolism of denervated muscle uses ketones and fatty acids as a source of energy for its limited requirements. The maintenance of TPN diaphorase activity and the absence of acid phpsphatase confirms the fact that muscle necrosis and regeneration do not occur after denervation. The enzyme changes are reversed when effective reinnervation is established.