Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Epilepsy: When the neuron's doorman allows too much in

19.11.2015

In epilepsy, nerve cells or neurons lose their usual rhythm, and ion channels, which have a decisive influence on their excitability, are involved. A team of researchers under the direction of the University of Bonn has now discovered a new mechanism for influencing ion channels in epilepsy. They found that spermine inside neurons dampens the neurons excitability. In epilepsy, spermine levels decrease, causing hyperexcitability. The researchers hope that their findings can be exploited to develop new therapies for epilepsies. They are reporting their findings in "The Journal of Neuroscience".

In Germany, approximately one out of a hundred people suffer from epilepsy and one out of twenty suffer a seizure at least once during their lifetime. Seizures occur when many nerve cells in the brain fire in synchrony.


This is how a neuron from the hippocampus of a rat looks like. The cell and it's extenive processes are visulaised using a fluorescent dye, filled via a glass pipette.

(c) Photo: AG Heinz Beck/Uni Bonn

Scientists are searching for the causes leading to this simultaneous excitation of brain cells. Researchers at the Department of Epileptology, the Institute for Neuropathology and the Institute for Molecular Psychiatry, together with the Caesar Research Center and the Hebrew University (Israel) have discovered a mechanism which previously was not thought to be involved in the development of epilepsy.

"Doormen" determine how many sodium ions are allowed in

Neurons integrate many inputs together to then determine an appropriate output, and sodium channels play a key role in both processes. "They play an important role in the excitation of nerve cell axons and signal transfer between various cells," says Prof. Dr. Heinz Beck, who conducts research in experimental epileptology at the Department of Epileptology, at the Life & Brain center and the German Center for Neurodegenerative Diseases (DZNE).

Like a type of door, sodium channels allow sodium ions to flow into nerve cells through tiny pores. They consist of large protein complexes located in the membranes of nerve cells. The scientists found a large increase in a certain sodium influx which significantly increased the excitability of cells in the epileptic animal.

For this reason, scientists working with Prof. Beck initially compared the sodium channel proteins from the brains of epileptic rats to those of healthy animals. "However, this did not reveal any increased formation of sodium channel proteins, which could have explained the overexcitation of nerve cells." reports the epilepsy researcher.

After a long search, the team of researchers found a completely different group of substances: the polyamines. Spermine belongs to this group; it is produced in cells and plugs the pores of the sodium channels from within. like a doorman. In this case, the influx of sodium ions is blocked and the excitation of the nerve cells is reduced.

Overexcitation is attenuated through administration of spermine

The scientists investigated how much of the seizure-inhibiting substance is present in the nerve cells of rats suffering from epilepsy and compared the values to those of healthy animals. "The amount of spermine in the cells of the hippocampus was significantly reduced in diseased animals as compared to the healthy animals," report the lead authors Dr. Michel Royeck and Dr. Thoralf Optiz from Dr. Beck's team. “Furthermore, the reduced spermine in the nerve cell led to increased excitability; the cells were more sensitive to input and generated more output” said fellow lead author Dr. Tony Kelly. The investigators tested this important finding, compensating for the deficiency in the nerve cells of epileptic rats by adding spermine back into the cell. As a result, the increase in sodium currents was reversed and the excitability of the neuron returned to normal.

The lower level of spermine in the epileptic rat’s brain was evidently caused by an upregulation of spermidine/spermine-N(1)-acetyltransferase. This enzyme breaks down the spermine which is important in the control of sodium channels. According to the scientists, this result could be a potential starting point for novel epilepsy therapies. "If a substance was available to reduce the activity of acetyltransferase back to normal levels, the lack of spermine and thus the symptoms of epilepsy could be mitigated," speculates Prof. Beck. However, concrete therapeutic applications are still a long way off.

Publication: Downregulation of Spermine Augments Dendritic Persistent Sodium Currents and Synaptic Integration after Status Epilepticus, The Journal of Neuroscience, DOI: 10.1523/JNEUROSCI.0493-15.2015

Media contact information:

Prof. Dr. Heinz Beck
University Hospital for Epileptology, Life & Brain Center,
German Center for Neurodegenerative Diseases
Spokesperson for Collaborative Research Center 1089
Tel. ++49-228-6885215
E-Mail: Heinz.Beck@ukb.uni-bonn.de

Dr. Tony Kelly
University Hospital for Epileptology, Life & Brain Center,
Tel. ++49-228-6885276
E-Mail: tony.kelly@ukb.uni-bonn.de

Johannes Seiler | idw - Informationsdienst Wissenschaft
Further information:
http://www.uni-bonn.de

More articles from Life Sciences:

nachricht Rainbow colors reveal cell history: Uncovering β-cell heterogeneity
22.09.2017 | DFG-Forschungszentrum für Regenerative Therapien TU Dresden

nachricht The pyrenoid is a carbon-fixing liquid droplet
22.09.2017 | Max-Planck-Institut für Biochemie

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: The pyrenoid is a carbon-fixing liquid droplet

Plants and algae use the enzyme Rubisco to fix carbon dioxide, removing it from the atmosphere and converting it into biomass. Algae have figured out a way to increase the efficiency of carbon fixation. They gather most of their Rubisco into a ball-shaped microcompartment called the pyrenoid, which they flood with a high local concentration of carbon dioxide. A team of scientists at Princeton University, the Carnegie Institution for Science, Stanford University and the Max Plank Institute of Biochemistry have unravelled the mysteries of how the pyrenoid is assembled. These insights can help to engineer crops that remove more carbon dioxide from the atmosphere while producing more food.

A warming planet

Im Focus: Highly precise wiring in the Cerebral Cortex

Our brains house extremely complex neuronal circuits, whose detailed structures are still largely unknown. This is especially true for the so-called cerebral cortex of mammals, where among other things vision, thoughts or spatial orientation are being computed. Here the rules by which nerve cells are connected to each other are only partly understood. A team of scientists around Moritz Helmstaedter at the Frankfiurt Max Planck Institute for Brain Research and Helene Schmidt (Humboldt University in Berlin) have now discovered a surprisingly precise nerve cell connectivity pattern in the part of the cerebral cortex that is responsible for orienting the individual animal or human in space.

The researchers report online in Nature (Schmidt et al., 2017. Axonal synapse sorting in medial entorhinal cortex, DOI: 10.1038/nature24005) that synapses in...

Im Focus: Tiny lasers from a gallery of whispers

New technique promises tunable laser devices

Whispering gallery mode (WGM) resonators are used to make tiny micro-lasers, sensors, switches, routers and other devices. These tiny structures rely on a...

Im Focus: Ultrafast snapshots of relaxing electrons in solids

Using ultrafast flashes of laser and x-ray radiation, scientists at the Max Planck Institute of Quantum Optics (Garching, Germany) took snapshots of the briefest electron motion inside a solid material to date. The electron motion lasted only 750 billionths of the billionth of a second before it fainted, setting a new record of human capability to capture ultrafast processes inside solids!

When x-rays shine onto solid materials or large molecules, an electron is pushed away from its original place near the nucleus of the atom, leaving a hole...

Im Focus: Quantum Sensors Decipher Magnetic Ordering in a New Semiconducting Material

For the first time, physicists have successfully imaged spiral magnetic ordering in a multiferroic material. These materials are considered highly promising candidates for future data storage media. The researchers were able to prove their findings using unique quantum sensors that were developed at Basel University and that can analyze electromagnetic fields on the nanometer scale. The results – obtained by scientists from the University of Basel’s Department of Physics, the Swiss Nanoscience Institute, the University of Montpellier and several laboratories from University Paris-Saclay – were recently published in the journal Nature.

Multiferroics are materials that simultaneously react to electric and magnetic fields. These two properties are rarely found together, and their combined...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

“Lasers in Composites Symposium” in Aachen – from Science to Application

19.09.2017 | Event News

I-ESA 2018 – Call for Papers

12.09.2017 | Event News

EMBO at Basel Life, a new conference on current and emerging life science research

06.09.2017 | Event News

 
Latest News

Rainbow colors reveal cell history: Uncovering β-cell heterogeneity

22.09.2017 | Life Sciences

Penn first in world to treat patient with new radiation technology

22.09.2017 | Medical Engineering

Calculating quietness

22.09.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>