A importância do sistema nervoso simpático na unidade motora e a utilização de seus agonistas no tratamento das Síndromes Miastênicas Congênitas

Abstract

Acetylcholine and its receptors are responsible for the communication between the Central Nervous System and skeletal muscles in mammals, through the Neuromuscular Junction. Disturbances in this communication can cause diseases that affect the neuromuscular system, such as Congenital Myasthenic Syndromes (CMSs). CMSs are a group of rare diseases that affect the NMJ and the usual treatment is the use of anticholinesterase drugs. However, its effects are lost over time. Recent discoveries have highlighted the importance of the sympathetic nervous system and its receptors in the physiology and diseases that affect the motor unit. Under normal conditions, β2-adrenergic receptors are involved in important processes in the motor endplate and in skeletal muscle physiology. Previous works from others and from our group have highlighted the importance of using β2-adrenergic agonists for the treatment of CMSs. Although the results are positive, the role of the sympathetic system and β2-adrenergic receptors in both the physiology of the motor unit and the treatment of CMSs is still unknown. In this work, we evaluated motor changes at the behavioral and motor unit level in knockout animals for β2-adrenergic receptors, demonstrating that the lack of these receptors causes several alterations in the animals. We also evaluated the use of a β2-adrenergic agonist in the treatment of mnVAChT-KD animals, a new model of SMC of presynaptic origin, through the deletion of VAChT (vesicular acetylcholine transporter) specifically in α-motoneurons. We observed that despite not being able to reverse the myasthenic condition, the β2-adrenergic agonist caused several changes in the components of the motor unit of the treated animals. Taken together, these findings demonstrate the importance of the sympathetic system and β2-adrenergic receptors in homeostasis and in the treatment of neuromuscular diseases.