Muscle atrophy is associated with cervical spinal motoneuron loss in BACHD mouse model for Huntington's disease

Abstract

Involuntary choreiform movements are clinical hallmark of Huntington's disease, an autosomal dominant neurodegenerative disorder caused by an increased number of CAG trinucleotide repeats in the huntingtin gene. Involuntary movements start with an impairment of facial muscles and then affect trunk and limbs muscles. Huntington's disease symptoms are caused by changes in cortex and striatum neurons induced by mutated huntingtin protein. However, little is known about the impact of this abnormal protein in spinal cord motoneurons that control movement. Therefore, in this study we evaluated abnormalities in the motor unit (spinal cervical motoneurons, motor axons, neuromuscular junctions and muscle) in a mouse model for Huntington's disease (BACHD). Using light, fluorescence, confocal, and electron microscopy, we showed significant changes such as muscle fibers atrophy, fragmentation of neuromuscular junctions, axonal alterations, and motoneurons death in BACHD mice. Noteworthy, the surviving motoneurons from BACHD spinal cords were smaller than WT. We suggest that this loss of larger putative motoneurons is accompanied by a decrease in the expression of fast glycolytic muscle fibers in this model for Huntington's disease. These observations show spinal cord motoneurons loss in BACHD that might help to understand neuromuscular changes in Huntington's disease.

Keywords: BACHD; motoneuron; neuromuscular junctions; spinal cord; sternomastoid muscle.