Modulation of the Acetylcholine Receptor Clustering Pathway Improves Neuromuscular Junction Structure and Muscle Strength in a Mouse Model of Congenital Myasthenic Syndrome.

Introduction: Congenital myasthenic syndromes (CMS) are a diverse group of inherited neuromuscular disorders characterized by a failure of synaptic transmission at the neuromuscular junction (NMJ). CMS often present early with fatigable weakness and can be fatal through respiratory complications. The AGRN gene is one of over 30 genes known to harbor mutations causative for CMS. In this study, we aimed to determine if a compound (NT1654), developed to stimulate the acetylcholine receptor (AChR) clustering pathway, would benefit a mouse model of CMS caused by a loss-of-function mutation in Agrn (Agrn nmf380 mouse). Methods: Agrn nmf380 mice received an injection of either NT1654 or vehicle compound daily, with wild-type litter mates used for comparison. Animals were weighed daily and underwent grip strength assessments. After 30 days of treatment animals were sacrificed, and muscles collected. Investigations into NMJ and muscle morphology were performed on collected tissue. Results: While minimal improvements in NMJ ultrastructure were observed with electron microscopy, gross NMJ structure analysis using fluorescent labelling and confocal microscopy revealed extensive postsynaptic improvements in Agrn nmf380 mice with NT1654 administration, with variables frequently returning to wild type levels. An improvement in muscle weight and myofiber characteristics helped increase forelimb grip strength and body weight. Conclusions: We conclude that NT1654 restores NMJ postsynaptic structure and improves muscle strength through normalization of muscle fiber composition and the prevention of atrophy. We hypothesize this occurs through the AChR clustering pathway in Agrn nmf380 mice. Future studies should investigate if this may represent a viable treatment option for patients with CMS, especially those with mutations in proteins of the AChR clustering pathway.

The relative effectiveness of computer-based and traditional resources for education in anatomy.

There is increasing use of computer-based resources to teach anatomy, although no study has compared computer-based learning to traditional. In this study, we examine the effectiveness of three formats of anatomy learning: (1) a virtual reality (VR) computer-based module, (2) a static computer-based module providing Key Views (KV), (3) a plastic model. We conducted a controlled trial in which 60 undergraduate students had ten minutes to study the names of 20 different pelvic structures. The outcome measure was a 25 item short answer test consisting of 15 nominal and 10 functional questions, based on a cadaveric pelvis. All subjects also took a brief mental rotations test (MRT) as a measure of spatial ability, used as a covariate in the analysis. Data were analyzed with repeated measures ANOVA. The group learning from the model performed significantly better than the other two groups on the nominal questions (Model 67%; KV 40%; VR 41%, Effect size 1.19 and 1.29, respectively). There was no difference between the KV and VR groups. There was no difference between the groups on the functional questions (Model 28%; KV, 23%, VR 25%). Computer-based learning resources appear to have significant disadvantages compared to traditional specimens in learning nominal anatomy. Consistent with previous research, virtual reality shows no advantage over static presentation of key views.