Acetylcholine receptors and nerve terminal distribution at the neuromuscular junction of non-obese diabetic mice

Abstract

Skeletal muscle is one of the main targets of the metabolic alterations in diabetes, in which protein synthesis is markedly reduced followed by increased proteolysis. Ultrastructural and functional changes in the presynaptic compartment of the neuromuscular junction (NMJ) have been demonstrated, but little attention has been paid to the proteins in the postsynaptic muscle fiber membrane. In the present work, we studied the changes in acetylcholine receptors (AChRs) and nerve terminal distribution in the NMJ of non-obese diabetic (NOD) mice. The sternomastoid muscles of adult female NOD mice were double-labeled for AChR and nerve terminal observation by fluorescence and reflected light confocal microscopy. In 62.4% of the diabetic endplates, AChR branches broke apart into receptor islands that stained less than in the normal mice. These patches had regular junctional folds. At most of the endplates studied, the nerve terminals colocalized with AChRs, and sprouts were seen in 10% of the diabetic endplates. The intramuscular nerve branches and axons in the nerve to the sternomastoid muscle showed no degenerative disorders. These results suggest that metabolic alterations in the diabetic muscle fiber can affect the distribution and expression of molecules, such as AChRs, in the postsynaptic membrane of the neuromuscular junction. © 2002 Wiley-Liss, Inc.