Ricerc@Sapienza

The connection between muscle and nerve is a biological mechanism severely impaired in many pathological conditions, as aging and Amyotrophic Lateral Sclerosis (ALS). Investigating the functionality of neuron conduction and muscle contraction is crucial in all those diseases where neuromuscular junction (NMJ) is altered. The NMJ fatigue is most often studied on neuromuscular disease animal models as a response to repeated stimulations in isometric conditions, comparing muscle contractile response elicited by two electrical stimulations, one on muscle membrane (direct) and the other through the nerve (indirect). However, the condition that better reflects body movements is the isotonic one. To date, in the literature, the isotonic fatigue test is only performed by repeatedly stimulating the muscle to lift a load equal to one-third of its maximal force (optimal force), a value proposed as the best representative of the force at which the tissue develops its maximum power. In view of this, the aim of this project is to devise a new experimental technique for NMJ functionality characterization during isotonic fatigue. Moreover, a software will be developed in LabVIEW 2019 to provide a real-time measurement of the maximum power the muscle is able to generate, both directly and indirectly, aiming at fatiguing the muscle at its own exact optimal force. Indeed, the experimental value of the optimal force will be applied as a constant load during the isotonic fatigue test. Finally, the isotonic fatigue protocol will be employed to test mouse models of Amyotrophic Lateral Sclerosis (SOD1G93A) at different stages of the disease progression, thus evaluating the impaired communication between muscle and nerve in a condition which better mimics the fatigue occurring in-vivo during muscle dynamic activity.