The Study of Genetic Susceptibility and Mitochondrial Dysfunction in Mesial Temporal Lobe Epilepsy

AbstractThe aim of this study is to investigate the mitochondrial dysfunction and pathogenic role of the mitochondrial genome in the progression of mesial temporal lobe epilepsy (MTLE) in vivo and in vitro. Mitochondrial DNA (mtDNA) and nuclear DNA were detected in the hippocampal samples and peripheral blood of patients with MTLE. Mitochondrial functions were detected in vivo and in vitro. In 20 patients with MTLE, mtDNA mutations involving single or multiple deletions in the hippocampus were found in 5 patients but were not detected in the peripheral blood. Two patients carried pathogenic mutations ofRELN, both in the hippocampus and blood. A pathogenic mutation ofDNA2 was found in the hippocampus of the 2 patients with multiple deletions but not in the blood samples. The mtDNA copy numbers showed dynamic changes in the MTLE models. In MTLE patients, low metabolism in mesial temporal lobe and hippocampus was observed by using PET-CT. Under electron microscope, the mitochondrial cristae were disordered, the density of mitochondrial matrix decreased and even vacuolated in the hippocampus neurons. In the MTLE rat models, there were dynamic changes in mitochondrial morphology; the ATP production rate decreased in the acute phase, the latent phase, and the chronic phase. Mitochondrial enzyme complex I activity decreased in both acute and chronic phases, and there was no significant difference in latent period. Decreased mitochondrial membrane potential and calcium homeostasis we...

Source: Molecular Neurobiology - July 5, 2020 Category: Neurology Source Type: research