Nav: Home

Trinity College Dublin researchers describe the first model of mitochondrial epilepsy

February 15, 2019

Dublin, Tuesday, February 12th, 2019 - Researchers from Trinity College Dublin have become the first to describe a model of mitochondrial epilepsy which raises hope for better therapies for patients with this incapacitating condition. Their paper has been published in BRAIN, the peer-reviewed international journal of neurology.

Mitochondrial disease is one of the most common forms of genetic diseases, affecting one in 9,000 births in Ireland with debilitating consequences. One quarter of patients with mitochondrial disease have epilepsy which is often severe and resistant towards conventional antiepileptic drugs.

Despite the severity of this epilepsy, up to now there have been no animal models available to provide a mechanistic understanding of the condition.

That is set to change though as researchers at Trinity can now explain the important role that astrocytes play in seizure generation. To date, astrocytes, the characteristic star-shaped glial cells found in the brain and spinal cord, have been seen as 'supporting-cells', playing a largely passive assisting role in the brain. This research shows however that they actually play a central role in driving seizure generation in mitochondrial epilepsy.

The researchers were able to recreate a novel brain slice model by the application of an astrocytic-specific aconitase inhibitor, fluorocitrate, concomitant with mitochondrial respiratory inhibitors, rotenone and potassium cyanide. The model was robust and exhibited both face and predictive validity.

The team then used the model to assess the role that astrocytes play in seizure generation and demonstrated the involvement of the GABA-glutamate-glutamine cycle, which regulates how chemical transmitters are released from neurons and then taken up by the supporting cells; the astrocytes.

Notably, glutamine appears to be an important intermediary molecule between the neuronal and astrocytic compartment in the regulation of GABAergic inhibitory tone.

Finally, the team found that a deficiency in glutamine synthetase is an important part of the pathogenic process for seizure generation in both the brain slice model and the human neuropathological study.

Explaining the importance of the research, Ellen Mayston Bates Professor of Neurophysiology of Epilepsy at Trinity, Mark Cunningham said: "We believe this is important and novel research as it produces, for the first time, a model of mitochondrial epilepsy which captures features observed in patients. The model provides mechanistic insights, demonstrating the role of astrocytes in this pathological activity."

Looking ahead and considering how this research translates to treat those with mitochondrial epilepsy, Professor Cunningham said: "We believe this work is important in providing new avenues with regard to producing better therapies for this condition. Future work will develop the model so that it can be used to stratify novel anti-seizure drugs in a tailored manner for patients diagnosed with mitochondrial disorders and who phenotypically exhibit epilepsy."
-end-
Paper published in BRAIN journal at: https://doi.org/10.1093/brain/awy320

Contact:


Ciara O'Shea, Media Officer, Trinity College Dublin, at COSHEA9@tcd.ie, +353 -1-8964337

Professor Mark Cunningham, Trinity College Dublin, at mark.cunningham@tcd.ie, +353-1- 896 8569)

Trinity College Dublin

Related Epilepsy Articles:

Good news for kids with epilepsy
There's good news for kids with epilepsy. While several new drugs have come out in the last several years for adults with epilepsy, making those drugs available for children and teenagers has been delayed due to the challenges of testing new drugs on children.
People with epilepsy: Tell us about rare risk of death
People with epilepsy want their health care providers to tell them about a rare risk of death associated with the disorder, according to a preliminary study released today that will be presented at the American Academy of Neurology's 69th Annual Meeting in Boston, April 22 to 28, 2017.
New epilepsy gene network identified by scientists
Scientists have discovered a gene network in the brain associated with epilepsy.
Epilepsy -- why do seizures sometimes continue after surgery?
New research from the University of Liverpool, published in the journal Brain, has highlighted the potential reasons why many patients with severe epilepsy still continue to experience seizures even after surgery.
Redox biomarker could predict progression of epilepsy
Approximately 2.9 million people in the United States suffer from epilepsy, according to the CDC.
More Epilepsy News and Epilepsy Current Events

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Erasing The Stigma
Many of us either cope with mental illness or know someone who does. But we still have a hard time talking about it. This hour, TED speakers explore ways to push past — and even erase — the stigma. Guests include musician and comedian Jordan Raskopoulos, neuroscientist and psychiatrist Thomas Insel, psychiatrist Dixon Chibanda, anxiety and depression researcher Olivia Remes, and entrepreneur Sangu Delle.
Now Playing: Science for the People

#537 Science Journalism, Hold the Hype
Everyone's seen a piece of science getting over-exaggerated in the media. Most people would be quick to blame journalists and big media for getting in wrong. In many cases, you'd be right. But there's other sources of hype in science journalism. and one of them can be found in the humble, and little-known press release. We're talking with Chris Chambers about doing science about science journalism, and where the hype creeps in. Related links: The association between exaggeration in health related science news and academic press releases: retrospective observational study Claims of causality in health news: a randomised trial This...