Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Dysfunction in cerebellar Calcium channel causes motor disorders and epilepsy

21.03.2013
One ion channel, many diseases
RUB researchers report in the “Journal of Neuroscience”

A dysfunction of a certain Calcium channel, the so called P/Q-type channel, in neurons of the cerebellum is sufficient to cause different motor diseases as well as a special type of epilepsy. This is reported by the research team of Dr. Melanie Mark and Prof. Dr. Stefan Herlitze from the Ruhr-Universität Bochum.

They investigated mice that lacked the ion channel of the P/Q-type in the modulatory input neurons of the cerebellum. “We expect that our results will contribute to the development of treatments for in particular children and young adults suffering from absence epilepsy”, Melanie Mark says. The research team from the Department of General Zoology and Neurobiology reports in the “Journal of Neuroscience”.

P/Q-type channel defects cause a range of diseases

“One of the main challenging questions in neurobiology related to brain disease is in which neuronal circuit or cell-type the diseases originate,” Melanie Mark says. The Bochum researchers aimed at answering this question for certain motor disorders that are caused by cerebellar dysfunction. More specifically, they investigated potential causes of motor incoordination, also known as ataxia, and motor seizures, i.e., dyskinesia. In a previous study in 2011, the researchers showed that a certain Calcium channel type, called P/Q-type channel, in cerebellar neurons can be the origin of the diseases. The channel is expressed throughout the brain, and mutations in this channel cause migraines, different forms of epilepsy, dyskinesia, and ataxia in humans.

Disturbing cerebellar output is sufficient to cause different diseases

“Surprisingly, we found in 2011 that the loss of P/Q-type channels, specifically in the sole output pathway of the cerebellar cortex, the Purkinje cells, not only leads to ataxia and dyskinesia, but also to a disease often occurring in children and young adults, absence epilepsy,” Dr. Mark says. The research team thus hypothesized that disturbing the output signals of the cerebellum is sufficient to cause the major disease phenotypes associated with the P/Q-type channel. In other words, P/Q-type channel mutations in the cerebellum alone can elicit a range of diseases, even when the same channels in other brain regions are intact.

Disturbing the input to the cerebellum has similar effects as disturbing the output

Mark’s team has now found further evidence for this hypothesis. In the present study, the biologists did not disturb the output signals, i.e., the Purkinje cells, directly, but rather the input to these cells. The Purkinje cells are modulated by signals from other neurons, amongst others from the granule cells. “This modulatory input to the Purkinje cells is important for the proper communication between neurons in the cerebellum,” Melanie Mark explains. In mice, the researchers disturbed the input signals by genetically altering the granule cells so that they did not express the P/Q-type channel. Like disturbing the cerebellar output in the 2011 study, this manipulation resulted in ataxia, dyskinesia, and absence epilepsy. “The results provide additional evidence that the cerebellum is involved in initiating and/or propagating neurological deficits”, Mark sums up. “They also provide an animal model for identifying the specific pathways and molecules in the cerebellum responsible for causing these human diseases.”

Bibliographic record

T. Maejima, P. Wollenweber,L.U.C. Teusner, J.L. Noebels, S. Herlitze, M.D. Mark (2013): Postnatal loss of P/Q-type channels confined to rhombic-lip-derived neurons alters synaptic transmission at the parallel fiber to Purkinje Cell synapse and replicates genomic Cacna1a mutation phenotype of ataxia and seizures in mice, The Journal of Neuroscience, doi: 10.1523/JNEUROSCI.5442-12.2013

Further information

Dr. Melanie Mark, Department of General Zoology and Neurobiology, Faculty of Biology and Biotechnology at the Ruhr-Universität, 44780 Bochum, Germany, Tel. +49/234/32-27913, E-Mail: melanie.mark@rub.de

Prof. Dr. Stefan Herlitze, Department of General Zoology and Neurobiology, Faculty of Biology and Biotechnology at the Ruhr-Universität, 44780 Bochum, Germany, Tel. +49/234/32-24363, E-Mail: stefan.herlitze@rub.de

Editorial journalist: Dr. Julia Weiler

Dr. Josef König | idw
Further information:
http://www.ruhr-uni-bochum.de

More articles from Life Sciences:

nachricht Cryo-electron microscopy achieves unprecedented resolution using new computational methods
24.03.2017 | DOE/Lawrence Berkeley National Laboratory

nachricht How cheetahs stay fit and healthy
24.03.2017 | Forschungsverbund Berlin e.V.

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Giant Magnetic Fields in the Universe

Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.

The results will be published on March 22 in the journal „Astronomy & Astrophysics“.

Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...

Im Focus: Tracing down linear ubiquitination

Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.

Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...

Im Focus: Perovskite edges can be tuned for optoelectronic performance

Layered 2D material improves efficiency for solar cells and LEDs

In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...

Im Focus: Polymer-coated silicon nanosheets as alternative to graphene: A perfect team for nanoelectronics

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...

Im Focus: Researchers Imitate Molecular Crowding in Cells

Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to simulate these confined natural conditions in artificial vesicles for the first time. As reported in the academic journal Small, the results are offering better insight into the development of nanoreactors and artificial organelles.

Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

International Land Use Symposium ILUS 2017: Call for Abstracts and Registration open

20.03.2017 | Event News

CONNECT 2017: International congress on connective tissue

14.03.2017 | Event News

ICTM Conference: Turbine Construction between Big Data and Additive Manufacturing

07.03.2017 | Event News

 
Latest News

Argon is not the 'dope' for metallic hydrogen

24.03.2017 | Materials Sciences

Astronomers find unexpected, dust-obscured star formation in distant galaxy

24.03.2017 | Physics and Astronomy

Gravitational wave kicks monster black hole out of galactic core

24.03.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>