New findings on multiple sclerosis—immune cells also attack neurons directly

Sep 23, 2010

Researchers in Germany have gained new insight into how the immune system causes damage associated with multiple sclerosis (MS). Using imaging tools which enable investigation of processes in living organisms, they were able to show a direct interaction between immune cells and neurons which play a significant role in neuronal injury. However, this direct interaction may respond to therapeutic intervention. The study by Dr Volker Siffrin and Professor Dr Frauke Zipp (formerly Max Delbrück Center for Molecular Medicine, MDC, Berlin-Buch, now University Medical Center Johannes Gutenberg University, Mainz) has now been published in the journal Immunity.

"The contribution of direct neuronal damage to MS pathology has been debated since the first description of the disease," explained Professor Frauke Zipp, senior author of the study. "Although many different theories about possible underlying mechanisms have been proposed – such as neuron damage being a secondary effect of the disrupted myelin sheath – actual events leading to neural damage are not well understood."

To investigate processes in the living organisms, Dr Zipp and her colleagues used 2-photon laser scanning microscopy (TPLSM), with which they studied the role immune cells play in neuronal damage in mice with experimental autoimmune encephalomyelitis, an animal model of multiple sclerosis. They observed direct synapse-like interactions between immune cells and neurons.

Th17 cells, immune cells which have been linked to autoimmune inflammation, induced elevated calcium levels in the neurons, which in the long run are toxic to the cells. Normally, calcium within the neuron plays a crucial role in exciting nerve cells as well as muscle cells.

This is significant because fluctuations in neuronal intracellular calcium levels that are linked to cell injury are partially reversible when the researchers expose the lesions of the animals to compounds used to treat excitotoxicity.

These results highlight a specific interaction between the immune system and the nervous system, implicating direct neuronal damage in autoimmune-mediated inflammation. "Our use of in vivo imaging during disease has led to the characterization of neuronal dysfunction as early and potentially reversible, and suggests that immune-mediated disturbances of the neurons themselves contribute to multiple sclerosis, in addition to interruptions in nerve cell transmission as a result of changes to the myelin sheath," Professor Zipp concluded.

"Furthermore, immune-mediated reversible calcium increases in neurons are a potential target for future therapeutics." However, it will take many years to find out if this is a strategy which will work for treating multiple sclerosis.

Source: News Release
Helmholtz Association of German Research Centres
September 23, 2010