Changes in lipid profiles of epileptic mouse model

Authors

Alicia Johnson, University of Nebraska-Lincoln
Ryan A. Grove, University of Nebraska-Lincoln
Deepak Madhavan, University of Nebraska Medical Center
Cory Honsinger Thomas Boone, University of Nebraska - LincolnFollow
Camila Pereira Braga, University of Nebraska - LincolnFollow
Hannah Kyllo, University of Nebraska Medical Center
Kaeli Samson, Creighton University School of MedicineFollow
Timothy Simeone, Creighton University School of Medicine
Tomáš Helikar, University of Nebraska–LincolnFollow
Corrine K. Hanson, University of Nebraska Medical Center
Jiri Adamec, University of Nebraska-LincolnFollow

Document Type

Article

Date of this Version

10-30-2023

Citation

Metabolomics. ; 16(10): 106. doi:10.1007/s11306-020-01729-4.

Comments

HHS Public Access

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.