Epilepsy: a new model revolutionizes understanding of the disease

A new study helps to better understand the role of certain brain cells, astrocytes, in triggering epileptic seizures of the mitochondrial form of the disease.

Epilepsy is not an unambiguous disease, but rather a grouping of different brain diseases that share the problem of having electric shock attacks of nerve cells (neurons) in different areas of the brain.

Researchers at Trinity College, Dublin, were the first to describe a new experimental model of mitochondrial epilepsy, a disease that involves certain brain cells whose role, astrocytes, is still poorly understood.

This discovery gives hope for the development of better treatments for patients suffering from this debilitating disease, but also other diseases. Their article was published in the international journal BRAIN.

The role of astrocytes

Mitochondrial disease is one of the most common forms of genetic disease, affecting one in 9,000 births in Ireland, with debilitating consequences. A quarter of patients with mitochondrial disease also have epilepsy, which is often severe and resistant to classical antiepileptics.

Despite the severity of this form of epilepsy, there has been no animal model available to date to provide a mechanistic understanding of the disease. This should change, as researchers at Trinity College can now explain the important role played by a neglected category of brain cells, astrocytes, in the onset of seizures.

Until now, astrocytes, star-shaped glial cells found in the brain and spinal cord, have been considered as simple "support cells" of neurons, playing a role of largely passive support. in the brain. This study shows that these cells really play a central role in the onset of seizures in mitochondrial epilepsy.

A new experimental model of epilepsy

The researchers were able to recreate a new experimental brain model in sections and applied fluorocitrate, an aconitase inhibitor, which is a specific astrocyte molecule, in combination with mitochondrial respiratory inhibitors, rotenone and cyanide. potassium. The model is robust and has predictive validity.

The team then used the model to evaluate the role of astrocytes in the onset of seizures. She has demonstrated the involvement of the GABA-glutamate-glutamine cycle, which governs how chemical emitters are released from neurons and then picked up by the supporting cells, the astrocytes. Glutamine appears to be an important binding molecule between the "neuronal" and "astrocytic" compartments of the brain in the regulation of GABAergic inhibitory tone.

Finally, the team discovered that glutamine synthetase deficiency was an important part of the pathogenic process of seizure emergence, both in the brain cut model and in the human neuropathological study.

Astrocytes, underestimated cells

Explaining the importance of research, Mark Cunningham, Professor of Neurophysiology of Epilepsy at Trinity College said, "We believe this research is important and innovative in that it produces, for the first time, a model of mitochondrial epilepsy. The model provides mechanistic information demonstrating the major role of astrocytes in this disease.

He also said: "We believe this work is important because it offers new perspectives for the development of more effective treatments for this disease. Future work will develop this model so that it is used to better prioritize new antiepileptic drugs to better individualize the treatment of patients with mitochondrial epilepsy. "

Video: Developing Smart Devices to Predict, Stop Seizures (November 2019).