Comparative Anatomy of the Neuromuscular Junction

Abstract

The neuromuscular junction (NMJ) is the area where a motor neuron synapses to a muscle fiber. The NMJ consists of a pre-synapse and a post-synapse which are separated by the synaptic cleft area. The ultimate function of the NMJ is to cause muscle contraction through the release of Acetylcholine neurotransmitters from the pre-synapse nerve terminal that will bind to the Acetylcholine receptors on the post-synapse. The NMJ has been extensively studied regarding its structure, function and pathology at a molecular and cellular level in many species including humans. However, comparative anatomy studies of the human NMJ and other species are limited. The mouse has been widely used in research as an experimental animal model, and great statistically significant differences when compared to human were reported. The aim of this thesis was to compare humans NMJs with mouse and sheep NMJs in the EDL, PL and S muscles in order to identify if there are any statistically significant differences between the two comparison groups as the NMJ is a primary target for many neurodegenerative diseases. The methods that were employed for this thesis were microdissection for myofiber acquisition (ethical approval was granted by the UK Home Office), immunohistochemistry for labelling the pre- and post-synapse, confocal microscopy to acquire NMJ micrographs and NMJ-morph platform and ImageJ software for NMJ morphometric analysis. One-way ANOVA test was used for statistical analysis. Statistical analysis showed that the mouse showed a statistically significant difference from human ranging from. In contrast, statistically, the sheep showed approximately of similarity to humans. Overall, the sheep was statistically strongly correlated to humans whereas mouse was significantly different. Future research is indispensable for understanding the structural and functional bases of the NMJ, and the identification of an animal model that accurately represents the human NMJ.