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The Influence of Exercise on Motor Nerve Terminal Degeneration in Elderly Mice

Wednesday 6 July 2016 12:54pm

Sarcopenia is a form of progressive muscle weakening which will affect us all as we age. The issue was touched on by Associate Professor Phil Sheard during brain week. As part of the 2016 BHRC conference one of his PhD students, Kathrine Nielsen, discussed her work in identifying some of the chemical changes which occur in these weakening muscles, and how exercise may reverse the issue.

The progressive muscle weakness of sarcopenia is caused by two independent processes: muscle fibre death, and muscle fibre atrophy. In her research Kathrine focused on muscle fibre atrophy, a process by which the fibres which make up your muscle start to shrink. This shrinkage occurs because the nerves which control the muscle fibre detach. Without information from the nerve the fibre can’t contract, it can’t add its strength to the rest of the muscle, and it begins to waste away.

But why does the nerve detach, and how can we stop it from detaching? Your nerves and muscle fibres use feedback signals in order to communicate with one another and, in some cases, to locate one another and remain closely linked. Kathrine examined one such feedback chemical, neurotrophin-4, and compared it to the activity of the muscle fibre by examining another neurotrophic factor, tyrosine kinase 4. Neurotrophin-4 supports the growth and survival of neurons, while tyrosine receptor kinase B (or tropomyosin receptor kinase – TrkB) manages the energy of the cell.

By comparing the motor neurons in the spinal cord of young and old mice Kathrine was able to see that neurotrophin-4 was present in high concentrations in the young mice, this factor was much more sparse in the old mice.

Without NT4 the neuron would become unhealthy and retract from the muscle fibre, and the distribution of TrkB in the motor neuron gives us a possible explanation for this. TrkB is usually present in the cytoplasm or at the cell surface of the motor neuron. This distribution appeared to be disrupted in motor neurons of old mice, where TrkB was found exclusively in the nucleus, a compartment of the cell in which this molecule has no known function.

Kathrine wanted to know what would happen to these muscle fibres if the old mice were encouraged to exercise. She gave the mice free access to a running wheel, and over the course of the experiment the mice slowly but surely increased the distance they ran each day. When Kathrine later examined the muscle fibres of these elderly mice she found that innervation was maintained in old exercised mice compared to the non-exercised controls. This was explained by the additional finding that NT-4 levels were increased in motor neurons of elderly exercisers, along with the observation that TrkB in these same cells reverted to its' normal cytoplasmic distribution.

Muscle weakness can very easily spiral out of control. A loss of muscle mass can be discouraging and can increase our chance of injury through muscle strains, or simply just by increasing our chance of falls. While we will all progressively lose strength as we age, Kathrine’s research assures us that we do have some control over how fast that strength fades. It is never too late to get ourselves back on track. It is never too late to regain control of our bodies.


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