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New Findings on Multiple Sclerosis - Immune Cells Also Attack Neurons Directly

Researchers in Germany have gained new insight into how the immune system causes damage associated with multiple sclerosis (MS), an incurable neuroinflammatory disorder. 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 plays 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 (DOI 10.1016/j.immuni.2010.08.018)*.

sclerosis is an autoimmune disease in which a person’s own immune system
attacks the central nervous system. Symptoms of the disease are variable
depending on which nerves are affected, but often include muscle weakness,
walking difficulties, numbness and visual disturbances. Research has shown that
MS is caused by damage to the protective myelin sheath, an insulating substance
that surrounds nerve processes and is critical for transmission of nerve

has also indicated that direct damage to neurons is prominent in early disease
stages. “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.”

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

cells called Th17 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.

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

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 MS.

*In vivo imaging of partially reversible Th17 cell-induced neuronal dysfunction in the course of encephalomyelitis

Volker Siffrin,1,2* Helena Radbruch,2,3* Robert Glumm,2,3 Raluca Niesner,2,3 Magdalena Paterka,2 Josephine Herz,2,3 Tina Leuenberger,2 Sabrina M. Lehmann, 4 Sarah Luenstedt,2,3 Jan Leo Rinnenthal,2 Gregor Laube,4 Hervé Luche,5 Seija Lehnardt,4 Hans-Joerg Fehling,5 Oliver Griesbeck,6 Frauke Zipp1,2

* equal contribution

1Neurology Department, University Medical Center Mainz, Johannes Gutenberg University Mainz, 55131 Mainz, Germany

2Max Delbrück Center for Molecular Medicine Berlin-Buch, 13125 Berlin, Germany

3Charité – University Medical Center Berlin, 10117 Berlin, Germany

4Institute of Cell Biology and Neurobiology, Charité - University Medicine Berlin, 10117 Berlin, Germany

5Institute of Immunology, University Clinics Ulm, Ulm, Germany

6Max Planck Institute of Neurobiology, 82152 Martinsried, Germany

*Correspondence: (F.Z.), (V.S.)

University Medical Center Johannes Gutenberg University, Mainz

Immune cells (red) attack nerve cells of mice. This leads to lethally elevated calcium levels within the neurons. (Photo: Dr. Volker Siffrin/Copyright: MDC)

Barbara Bachtler
Press and Public Affairs
Max Delbrück Center for Molecular Medicine (MDC)
Robert-Rössle-Straße 10
13125 Berlin, Germany
Phone: +49 (0) 30 94 06 - 38 96
Fax: +49 (0) 30 94 06 - 38 33
Dr. Renée Dillinger-Reiter

Communication and Press
University Medical Center Mainz
Johannes Gutenberg University Mainz

Langenbeckstraße 1
55131 Mainz , Germany

Phone +49 (0) 6131 17-7428

Fax +49 (0) 6131 17-3496


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