Efficacy of Mitochondrial Transfer in Healing Toxin-Induced Damage to Neuromuscular Junction, an Empirical Study.

Abstract

Neuromuscular diseases and damage affect many people of all ages and are responsible for an exorbitant medical cost, more than $200 million annually. Accordingly, finding an appropriate model to investigate potential curative interventions is necessary. One currently used involves the application of toxic agents on skeletal muscle followed by mitochondrial transplant therapy. A question regarding this model is whether such toxins impact not only muscle tissue but also the neuromuscular junctions (NMJs) responsible for exciting the muscle tissue. This question was addressed here by forming four experimental groups of C57BL/six mice (10-14 per group) that were 8-12 weeks of age: 1) controls whose muscles had not been injured or treated, 2) muscles taken from mice that were injured and then treated with mitochondrial supplement, 3) muscles that had not been injured but were still treated with mitochondria, and 4) muscles that were injured and received no mitochondrial treatment. Several pre- and postsynaptic features of NMJs were subject to immunofluorescent staining procedures before having morphological features assessed with confocal microscopy. Results revealed that only postsynaptic acetylcholine (ACh) receptors showed any significant (p < 0.05) between-group differences, including decreased area size and perimeter length around ACh receptor clusters in injured NMJs. However, presynaptic nerve terminal branching was not different (p > 0.05) among treatment groups, and structural features were not different between groups with the exception of dispersion of postsynaptic receptors. Overall, these results suggest that skeletal muscles damaged with toxin accurately mimic what occurs during toxin-induced damage and post-injury recovery and can be used as a faithful model of occurrences during damage to NMJs as a result of muscle damage along with recovery from that insult.