Mitochondrial complex I deficiency in the epileptic focus of patients withtemporal lobe epilepsy

Mitochondria are cellular organelles crucial for energy supply and calcium homeostasis in neuronal cells, and their dysfunction causes seizure activit y in some rare human epilepsies. To directly test whether mitochondria resp iratory chain enzymes are abnormal in the most common form of chronic epile psy, temporal lobe epilepsy (TLE), living human brain specimens from 57 epi leptic patients and 2 nonepileptic controls were investigated. In TLE patie nts with a hippocampal epileptic focus, we demonstrated a specific deficien cy of complex I of the mitochondrial respiratory chain in the hippocampal C A3 region. In contrast, TLE patients with a parahippocampal epileptic focus showed reduced complex I activity only in parahippocampal tissue. Inhibito r titrations of the maximal respiration rate of intact human brain slices r evealed that the observed reduction in complex I activity is sufficient to affect the adenosine triphosphate production rate. The abnormal complex I a ctivity in the hippocampal CA3 region was paralleled by increased succinate dehydrogenase staining of neurons and marked ultrastructural abnormalities of mitochondria. Therefore, mitochondrial dysfunction is suggested to be s pecific for the epileptic focus and may constitute a pathomechanism contrib uting to altered excitability and selective neuronal vulnerability in TLE.