Study Reveals Key Role of TRIO Gene in Epileptic Encephalopathies
November 13, 2024
Article Published by Medical Xpress
In a new study from Université de Montréal, researchers studied the molecular and cellular mechanisms by which some infants develop epileptic encephalopathies and autism spectrum disorder. These neurodevelopmental disorders are due to a dysfunction in the development of GABAergic interneurons, cells that are scarce in the brain, but whose inhibitory role is crucial to the proper wiring of the cerebral cortex. In particular, mutations in the TRIO gene disrupt the migration of these interneurons. After developing a unique microscopy technique that enables real-time tracking of interneuron movement during the embryonic period, the researchers demonstrated that loss of function of the TRIO gene impairs interneuron migration, a key process in the formation of the cerebral cortex. “What we observe in mouse models with interneuron-specific TRIO deletion is that the affected cells move erratically and more slowly during the embryonic development, as if they don’t know where to go,” said postdoctoral fellow Lara Eid. “This prevents them from reaching their destination, so by the end of the migration, many areas of the cortex don’t have enough of these interneurons to properly exert their inhibitory role. “Children with TRIO–associated epileptic encephalopathy could benefit from targeted therapy or cell therapy aimed at restoring the number or function of interneurons,” said Dr. Elsa Rossignol, co-principal investigator of the study. “This data brings us a step closer to finding a treatment that will improve the outcome for affected children.”