Medium-Chain Triglycerides Supplementation Protects Epilepsy-Associated Behavioral Impairments in a Mouse Model

Presently there has been a growing interest in the development of dietary-based interventions as alternative therapies to combat chronic neurological conditions like epilepsy. Medium-chain triglycerides (MCT) are composed of three fatty acids attached to a glycerol backbone and have shown several beneficial effects in various neurological diseases. The present study investigated MCT supplementation's impact on seizure severity and associated neurobehavioral comorbidities in a pentylenetetrazole (PTZ) mouse kindling model. Mice were administered 35 mg/kg (i.p.) of PTZ every other day for kindling induction. The kindled mice were then subjected to MCT supplementation for over 25 days with seizure scoring at every 5th day following PTZ exposure. Behavioral analysis was initiated at the end of 25 days of the MCT supplementation. After that, lipid peroxidation assay, and, gene and protein expression studies were performed in the isolated hippocampus. MCT significantly decreased seizure severity scores compared to control. The treatment reduced immobility duration in the forced swim and tail suspension tests, indicating a reversal of seizures-associated depression-like behavior. A significant reduction in the percentage of spontaneous alternation was observed in the kindled control group in the T-maze test, which remained unchanged following MCT supplementation in the treated group. Furthermore, no change was observed in the locomotion and anxiety index of the kindled mice supplemented with MCT compared to the control group. In addition, the supplementation attenuated the altered hippocampal lipid peroxidation, and mRNA and protein levels of mTOR and Gsk-3β. The study concluded that MCT supplementation suppresses epileptic seizures and associated depression-like behavior in kindled mice via interacting mTOR and Gsk-3β signaling.