Multiple sclerosis (MS) is a chronic inflammatory disease that affects the central nervous system, in which nerve cells are attacked by the patient's own immune system. In many cases, the disease develops into a progressive form, which is characterized by a shift of pathology from the white matter to the gray matter, for instance, to the cerebral cortex. This phase of the disease has so far been difficult to treat and its underlying causes are poorly understood. Now, a research team led by Martin Kerschensteiner, Director of the Institute for Clinical Neuroimmunology at LMU, in cooperation with Thomas Misgeld (Technical University of Munich) and Doron Merkler (University of Geneva), has shown in a mouse model that inflammation of the gray matter leads to a decrease in nerve-cell activity, owing to the (potentially reversible) destruction of synapses. Targeted inhibition of specific types of immune cells can slow synapse damage down, and offers an interesting new therapeutic approach.

Loss of synapses—the structures that serve as functional contacts between nerve cells—is an early indicator of damage to the cerebral cortex in cases of progressive MS. The researchers therefore suspected that the synapses are the key to the neuronal damage that ensues in this stage of the disease. With the aid of various imaging techniques, the team was able to demonstrate that such widespread loss of synapses can be reproduced in a mouse model of MS. Moreover, their observations revealed that synaptic spines are destroyed by a specific type of immune cells. "These immune cells preferentially eliminate spines, which contain high levels of calcium. We assume that the inflammation reaction itself triggers an influx of calcium, which destabilizes the spines. These changes in late-stage MS are reminiscent of those that can also be observed during the early phases of neurodegeneration.

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John
Editorial Assistant
Immunogenetics Open Access