Changes in lipid profiles of epileptic mouse model

Alicia Johnson, Ryan A. Grove, Deepak Madhavan, Cory H.T. Boone, Camila Braga, Hannah Kyllo, Kaeli Samson, Kristina Simeone, Timothy Simeone, Tomas Helikar, Corrine K. Hanson, Jiri Adamec

Research output: Contribution to journalArticlepeer-review

Abstract

Introduction: Approximately 1% of the world’s population is impacted by epilepsy, a chronic neurological disorder characterized by seizures. One-third of epileptic patients are resistant to AEDs, or have medically refractory epilepsy (MRE). One non-invasive treatment that exists for MRE includes the ketogenic diet, a high-fat, low-carbohydrate diet. Despite the KD’s success in seizure attenuation, it has a few risks and its mechanisms remain poorly understood. The KD has been shown to improve metabolism and mitochondrial function in epileptic phenotypes. Potassium channels have implications in epileptic conditions as they have dual roles as metabolic sensors and control neuronal excitation. Objectives: The goal of this study was to explore changes in the lipidome in hippocampal and cortical tissue from Kv1.1-KO model of epilepsy. Methods: FT-ICR/MS analysis was utilized to examine nonpolar metabolome of cortical and hippocampal tissue isolated from a Kv1.1 channel knockout mouse model of epilepsy (n = 5) and wild-type mice (n = 5). Results: Distinct metabolic profiles were observed, significant (p < 0.05) features in hippocampus often being upregulated (FC ≥ 2) and the cortex being downregulated (FC ≤ 0.5). Pathway enrichment analysis shows lipid biosynthesis was affected. Partition ratio analysis revealed that the ratio of most metabolites tended to be increased in Kv1.1−/−. Metabolites in hippocampal tissue were commonly upregulated, suggesting seizure initiation in the hippocampus. Aberrant mitochondrial function is implicated by the upregulation of cardiolipin, a common component in the mitochondrial membrane. Conclusion: Generally, our study finds that the lipidome is changed in the hippocampus and cortex in response to Kv1.1-KO indicating changes in membrane structural integrity and synaptic transmission.

Original languageEnglish (US)
Article number106
JournalMetabolomics
Volume16
Issue number10
DOIs
StatePublished - Oct 1 2020

Keywords

  • Drug resistant epilepsy
  • Lipids
  • Metabolic profiling
  • Metabolomics
  • Seizure

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Clinical Biochemistry

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