Regulation of motor nerve terminal degeneration by neuromuscular activity in the SOD1 mouse model of MND

Description:

What this research means to you: It is becoming clear that the degeneration of motor neurones in MND starts at the connection between the neurone and the muscle, known as the neuromuscular synapse. This project aims to investigate the breakdown of these connections in an animal model of MND and to assess the effect of exercise on this process. Ultimately, this project could provide a better understanding of the disease process in MND and may also indicate how exercise might be used as therapy.

The researcher explains in more detail: Some patients with MND believe that they benefit from taking exercise. However, there are contradictory reports on the benefits of exercise on disease progression. Thus, a major question is: does exercise protect motor neurones and thereby delay or prevent their degeneration? Recent studies have shown that neuromuscular synapses are the first components of a motor neurone to degenerate in MND, both in patients and in the most well-characterised animal models of the disease. However, neuromuscular synaptic degeneration is not completely understood. In this project we will first carry out a systematic and comprehensive review of the structure of neuromuscular synapses as disease progresses in mice that model MND. Second, we will find out the relationship in time between the onset of degeneration of neuromuscular synapses and the loss of motor neurones in the spinal cord. Third, we will test whether exercise in the mouse model delays degeneration of motor nerve endings, preserving neuromuscular function and preventing motor neurone death in the long run. The results will lead to a better understanding of the steps leading to degeneration of motor neurones and may reveal the best ways of using exercise to benefit the quality and duration of life in people with MND.

Prof Ribchester's home page