Mitochondrial Glutamine Metabolism Drives Epileptogenesis in Primary Hippocampal Neurons.

ABSTRACT: All available antiseizure medications aim at symptomatic control of epilepsy, but there is no strategy to stop the development of the disease. The main reason is the lack of understanding of the epileptogenic mechanisms. Closing this knowledge gap is an essential prerequisite for developing disease-modifying therapies that can prevent the onset of epilepsy. Using primary cocultures of hippocampal neurons and glial cells derived from rat pups of either sex, we show that epileptiform paroxysmal depolarization shifts (PDS) induce neuronal glucose hypometabolism which is compensated for by increased glutaminolysis. Glutaminolysis not only provides sufficient ATP to support electrical activity but also leads to decreased vesicular glutamate release, thereby promoting neuronal hypersynchrony. Mo

SUBMITTER: Kubista H 

PROVIDER: S-EPMC12096049 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature