Caracterização das alterações morfofuncionais de unidades motoras de um modelo murino para doença de Huntington (BACHD)

Abstract

Huntington's disease is a complex neurodegenerative disorder characterized by motor dysfunction with severe muscle atrophy. The motor symptoms are progressive and attributed to the loss of striatal neurons in the brain, causing involuntary limbs, trunk and face movements. In Huntington’s disease, there is a polyglutamine expansion of huntingtin protein leading to the formation of mutated protein that interferes in several processes in cells leading them to the death. Despite the cause of the involuntary movements in Huntington’s disease be well established, it is known that both normal and mutated huntingtin are expressed outside the Central Nervous System, such as at the skeletal muscle. Thus, the aim of this study was to investigate possible changes in sternomastoid and tibialis anterior muscle’s motor units from a murine model for Huntington’s disease (BACHD) once this structure is directly involved in the execution of movements. We used behavioral tests, optical, fluorescence, confocal and electronic microscopy to investigate possible changes in the components of sternomastoid and tibialis anterior muscles motor units, such as motor neurons in the cervical and lumbar segment of the spinal cord, neuromuscular junctions and skeletal muscles. We first identified motor deficit in behavioral testes in BACHD mice. After, we observed in transgenic mice decrease in cervical and lumbar motoneurons number and atrophy. We also observed fragmentation, denervation and loss of pre and post-synaptic colocalization in neuromuscular junctions. In addition, we noticed that muscle atrophy that was accompanied by both changes in the pattern of the myosin heavy chain and muscle ultrastructural abnormalities in both muscle. Together, our results indicate that this muscle’ motor unit is also affected in all its components. These results can further contribute to new targets for therapeutic interventions focusing on peripheral structures related to movement.