Spatio-temporal imaging of calcium in degenerating nerves

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Axons are the long processes that link neurons together within our brain, spinal cord and peripheral nervous system, allowing neurons to communicate rapidly with one another. Naturally with such huge structures, there are significant logistical problems in maintaining axons. Failure to do so is the cause of a number of human neurological disorders, not only those where there is direct axonal injury such as spinal injury, but also many where the disorder is inherited such as motor neuron disease, or acquired such as exposure to neurotoxins. We are beginning to understand that the way in which axons die is similar in each of these seemingly unrelated circumstances. However, we do not yet fully understand what that mechanism is. Calcium ions are normally pumped out of all cells, including neurons, because high levels of calcium inside the cell are extremely dangerous. It is also pumped into specific 'stores' within cells, including inside the axon, from where it may be released and used to 'signal' certain events and processes so that the cell or axon can respond accordingly. We are investigating whether calcium is released from intra-axonal stores early in the degeneration process and whether this is required for axon degeneration. This is a very important issue because axons make up by far the largest part of most neurons and because they are essential for the function of that neuron and for the most part cannot be replaced if they are lost. In the longer term, understanding this process should lead to new ways to treat, or even prevent, a wide spectrum of neurodegenerative conditions.

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