Nerve degeneration by calcium ions may contribute to MS

enero 29, 2019
The permanent neurological deficits of multiple sclerosis patients largely depend on the extent of degeneration of long nerve fibers. A new study suggests that ruptures in the cell membrane initiate degeneration of long nerve fibers, resulting influx of calcium ions.

The degree of the patient´s disability, is critically dependent on the extent of nerve-fiber loss. Now researchers at the Institute of Clinical Neuroimmunology at Ludwig-Maximilians-Universitaet in Munich, and the Institute for Neuronal Cell Biology at the Technical University of Munich, working with an animal model of MS have shown that minuscule ruptures in the cell membrane allow calcium ions to percolate into the neuron, disrupting the ionic balance and ultimately killing the axon.

In previous studies, researchers observed that axons in inflammatory lesions often were swollen and subsequently fragmented. The researchers have now shown that the fate of these axons depends on their calcium content. Axons with an abnormally high concentration of calcium are more likely to undergo swelling and subsequent degeneration and less likely to recover from this state than axons with normal levels of the ion. In 10 percent of the axons examined, the calcium concentration was already increased prior to the onset of swelling. About half of the swollen axons were found to have high levels of intracellular calcium, and a correspondingly high risk of degeneration. The excess calcium is derived from the extracellular space and it enters the axon through nanoruptures in the cell membrane, as the team was able to demonstrate using a fluorescent dye coupled to a macromolecule. 

It is already known from studies of spinal cord injury that nerve cells have the capacity to repair ruptures caused by mechanical forces. Results of mouse model studies sometimes do not translate to humans and may be years away from being a marketable treatment. However, the researchers hope that a better understanding of the origins and repair of damaged nerve-cell membranes will bring them closer to identifying new targets for therapeutic interventions.

The new findings appear in the journal Neuron.
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