Article published in Science Blog
Epilepsy, one of the most common neurological disorders, is characterized by the spontaneous repetition of seizures caused by the hyperactivity of a group of neurons in the brain. Could we therefore reduce neuronal hyperactivity, and treat epilepsy, by reducing the amount of energy supplied to neurons and necessary for their proper functioning? This was tested by a team led by scientists from the University of Geneva (UNIGE) and the EPFL. The researchers discovered that, in mice, the seizures were actually exacerbated. They observed that a reduction in the amount of energy led to an increase in the level of calcium in neurons, making them hyperexcitable. These dysfunctions could be corrected when mice were fed a ketogenic diet, which is rich in lipids and has been used since antiquity. This work is published in the journal eLife.
Our brain, which represents only 2% of our body weight, consumes more than 20% of the sugar we ingest. This considerable need for sugar provides the energy necessary for the function of the billions of neurons responsible for the emission and propagation of nervous messages, via electrical signals. This conversion of sugar, and more precisely of glucose, into energy is carried out by the mitochondria, small intracellular organelles considered as the “energy factories” of the cell.
The laboratory of Jean-Claude Martinou, professor in the Department of Molecular and Cellular Biology at the Faculty of Science, is interested in how mitochondria work. His group had already discovered the universal carrier that allows pyruvate, a product of glucose catabolism, to enter into mitochondria. He is now investigating the role of the mitochondrial pyruvate carrier (MPC) in neuronal activity and whether a defect in the transport of pyruvate in mitochondria could be linked to certain neurological diseases, notably epilepsy.
The biologists administered a pro-epileptic drug, capable of inducing epileptic seizures, to normal mice and to mice whose cortical neurons lacked the MPC. In normal mice, injection of a low dose of the drug did not induce seizures. On the other hand, and contrary to the initial hypothesis, in mice lacking the MPC, very severe, even fatal, seizures occurred as soon as low doses of the pro-epileptic drug were administered.