Featured Research

from universities, journals, and other organizations

Biologists pave the way for improved epilepsy treatments

Date:
June 6, 2014
Source:
University of Toronto
Summary:
Biologists leading an investigation into the cells that regulate proper brain function, have identified and located the key players whose actions contribute to afflictions such as epilepsy and schizophrenia. The discovery is a major step toward developing improved treatments for these and other neurological disorders.

University of Toronto biologists leading an investigation into the cells that regulate proper brain function, have identified and located the key players whose actions contribute to afflictions such as epilepsy and schizophrenia. The discovery is a major step toward developing improved treatments for these and other neurological disorders.

“Neurons in the brain communicate with other neurons through synapses, communication that can either excite or inhibit other neurons,” said Professor Melanie Woodin in the Department of Cell and Systems Biology at the University of Toronto (U of T), lead investigator of a study published today in Cell Reports. “An imbalance among the levels of excitation and inhibition – a tip towards excitation, for example – causes improper brain function and can produce seizures. We identified a key complex of proteins that can regulate excitation-inhibition balance at the cellular level.”

This complex brings together three key proteins – KCC2, Neto2 and GluK2 – required for inhibitory and excitatory synaptic communication. KCC2 is required for inhibitory impulses, GluK2 is a receptor for the main excitatory transmitter glutamate, and Neto2 is an auxiliary protein that interacts with both KCC2 and GluK2. The discovery of the complex of three proteins is pathbreaking as it was previously believed that KCC2 and GluK2 were in separate compartments of the cell and acted independently of each other.

“Finding that they are all directly interacting and can co-regulate each other’s function reveals for the first time a system that can mediate excitation-inhibition balance among neurons themselves,” said Vivek Mahadevan, a PhD candidate in Woodin’s group and lead author of the study.

Mahadevan and fellow researchers made the discovery via biochemistry, fluorescence imaging and electrophysiology experiments on mice brains. The most fruitful technique was the application of an advanced sensitive gel system to determine native protein complexes in neurons, called Blue Native PAGE. The process provided the biochemical conditions necessary to preserve the protein complexes that normally exist in neurons. Blue Native PAGE is advantageous over standard gel electrophoresis, where proteins are separated from their normal protein complexes based on their molecular weights.

“The results reveal the proteins that can be targeted by drug manufacturers in order to reset imbalances that occur in neurological disorders such as epilepsy, autism spectrum disorder, schizophrenia and neuropathic pain,” said Woodin. “There is no cure for epilepsy; the best available treatments only control its effects, such as convulsions and seizures. We can now imagine preventing them from occurring in the first place.”

“It was the cellular mechanisms that determine the excitation-inhibition balance that needed to be identified. Now that we know the key role played by KCC2 in moderating excitatory activity, further research can be done into its occasional dysfunction and how it can also be regulated by excitatory impulses,” said Mahadevan.


Story Source:

The above story is based on materials provided by University of Toronto. Note: Materials may be edited for content and length.


Journal Reference:

  1. Vivek Mahadevan, JessicaC. Pressey, BrookeA. Acton, Pavel Uvarov, MichelleY. Huang, Jonah Chevrier, Andrew Puchalski, CaiweiM. Li, EvgueniA. Ivakine, MattiS. Airaksinen, Eric Delpire, RoderickR. McInnes, MelanieA. Woodin. Kainate Receptors Coexist in a Functional Complex with KCC2 and Regulate Chloride Homeostasis in Hippocampal Neurons. Cell Reports, 2014; DOI: 10.1016/j.celrep.2014.05.022

Cite This Page:

University of Toronto. "Biologists pave the way for improved epilepsy treatments." ScienceDaily. ScienceDaily, 6 June 2014. <www.sciencedaily.com/releases/2014/06/140606120405.htm>.
University of Toronto. (2014, June 6). Biologists pave the way for improved epilepsy treatments. ScienceDaily. Retrieved August 28, 2014 from www.sciencedaily.com/releases/2014/06/140606120405.htm
University of Toronto. "Biologists pave the way for improved epilepsy treatments." ScienceDaily. www.sciencedaily.com/releases/2014/06/140606120405.htm (accessed August 28, 2014).

Share This




More Mind & Brain News

Thursday, August 28, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Treadmill 'trips' May Reduce Falls for Elderly

Treadmill 'trips' May Reduce Falls for Elderly

AP (Aug. 28, 2014) Scientists are tripping the elderly on purpose in a Chicago lab in an effort to better prevent seniors from falling and injuring themselves in real life. (Aug.28) Video provided by AP
Powered by NewsLook.com
Alice in Wonderland Syndrome

Alice in Wonderland Syndrome

Ivanhoe (Aug. 27, 2014) It’s an unusual condition with a colorful name. Kids with “Alice in Wonderland” syndrome see sudden distortions in objects they’re looking at or their own bodies appear to change size, a lot like the main character in the Lewis Carroll story. Video provided by Ivanhoe
Powered by NewsLook.com
Stopping Schizophrenia Before Birth

Stopping Schizophrenia Before Birth

Ivanhoe (Aug. 27, 2014) Scientists have long called choline a “brain booster” essential for human development. Not only does it aid in memory and learning, researchers now believe choline could help prevent mental illness. Video provided by Ivanhoe
Powered by NewsLook.com
Personalized Brain Vaccine for Glioblastoma

Personalized Brain Vaccine for Glioblastoma

Ivanhoe (Aug. 27, 2014) Glioblastoma is the most common and aggressive brain cancer in humans. Now a new treatment using the patient’s own tumor could help slow down its progression and help patients live longer. Video provided by Ivanhoe
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins