A new study provides a better understanding of the role of certain brain cells, astrocytes, in triggering epileptic seizures in the mitochondrial form of the disease.
Epilepsy is not a one-size-fits-all disease, but rather a collection of different brain diseases that share the problem of having seizures of electrical discharges from nerve cells (neurons) in different areas of the brain.
Researchers from Trinity College, Dublin, were the first to describe a new experimental model of mitochondrial epilepsy, a disease that involves certain brain cells whose role is still poorly understood, the astrocytes.
This discovery gives hope for the development of better treatments for patients suffering from this debilitating disease, but also from other conditions. 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 suffering from a mitochondrial disease are also suffering from epilepsy, which is often severe and resistant to conventional antiepileptics.
Despite the severity of this form of epilepsy, until now there have been no animal models available to provide a mechanistic understanding of the disease. That should change, as Trinity College researchers can now explain the important role that an overlooked class of brain cells, astrocytes, play in causing seizures.
Until now, astrocytes, star-shaped glial cells found in the brain and spinal cord, have been thought of as mere “support cells” for neurons, playing a largely passive support role. in the brain. This study shows that these cells actually 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 model of a brain in sections and applied fluorocitrate, an aconitase inhibitor, which is a specific molecule of astrocytes, in combination with inhibitors of the mitochondrial airways, rotenone and cyanide of potassium. The model is robust and exhibits predictive validity.
The team then used the model to assess the role played by astrocytes in causing seizures. She demonstrated the involvement of the GABA-glutamate-glutamine cycle, which governs how chemical transmitters are released from neurons and then taken up by supporting cells, astrocytes. Glutamine appears to be an important binding molecule between the “neuronal” and “astrocyte” compartments of the brain in the regulation of GABAergic inhibitory tone.
Finally, the team found that glutamine synthetase deficiency was an important part of the pathogenic process of seizure onset, both in the brain slice model and in human neuropathological study.
Astrocytes, underestimated cells
Explaining the significance of the research, Mark Cunningham, Professor of Neurophysiology of Epilepsy at Trinity College said: “We believe this research is important and groundbreaking 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 insights for the development of more effective treatments in this disease. Future work will expand this model so that it can be used to better prioritize new antiepileptics to better individualize the treatment of patients with mitochondrial epilepsy.”
.