Changes in nerve excitability during disease progression in animal models of MND

Description:

What this research means to you: Irregular muscle twitching, known as fasciculation, is one symptom of MND and is caused by changes in the way nerve impulses are transmitted. These changes in nerve excitability are seen in people with MND. This project will investigate nerve impulse transmission in three different mouse models of MND as the disease progresses. This may ultimately allow a similar approach to be applied in people with MND, which could provide a diagnostic aid and a way of monitoring disease progression.

The researchers explain in more detail: The ease with which nerves transmit impulses, or their “excitability”, depends on special gateways that span a neurone’s outer wall and allow only particular types of charged particle to enter or leave. Prof Bostock and colleagues have already developed a non-invasive test that can detect disturbances of nerve excitability and distinguish which types of gateway are responsible. These changes in nerve excitability are seen in people with MND.

In people with MND, this method has revealed a complex pattern of dysfunction that is difficult to interpret, not least because neighbouring motor neurones can degenerate at different times. In mice that model MND, neighbouring motor neurones are affected by the disease in a more consistent manner, thus allowing us to gain a clearer insight into the processes at work. During an MND Association funded pilot study we have successfully used Prof Bostock’s test to follow changes in nerve excitability with age in normal mice. Preliminary findings in a particular type of mouse model of MND have provided good evidence of abnormalities in nerve excitability, although these differ from those seen in people with the disease.

To better understand the changes in patients, we would now like to complete the study of changes in relation to disease progression in our first mouse model, and apply excitability testing to other mouse models of MND. We also plan to investigate a possible reason for the differences in abnormality between the mouse model and people with MND.