title: Metabolic Therapy for Temporal Lobe Epilepsy in a Dish: Investigating Mechanisms of Ketogenic Diet using Electrophysiological Recordings in Hippocampal Slices.
abstract: The hippocampus is prone to epileptic seizures and is a key brain region and experimental platform for investigating mechanisms associated with the abnormal neuronal excitability that characterizes a seizure. Accordingly, the hippocampal slice is a commonin vitromodel to study treatments that may prevent or reduce seizure activity. The ketogenic diet is a metabolic therapy used to treat epilepsy in adults and children for nearly 100 years; it can reduce or eliminate even severe or refractory seizures. New insights into its underlying mechanisms have been revealed by diverse types of electrophysiological recordings in hippocampal slices. Here we review these reports and their relevant mechanistic findings. We acknowledge that a major difficulty in using hippocampal slices is the inability to reproduce precisely thein vivocondition of ketogenic diet feeding in anyin vitropreparation, and progress has been made in thisin vivo/in vitrotransition. Thus far at least three different approaches are reported to reproduce relevant diet effects in the hippocampal slices: (1) direct application of ketone bodies; (2) mimicking the ketogenic diet condition during a whole-cell patch-clamp technique; and (3) reduced glucose incubation of hippocampal slices from ketogenic diet-fed animals. Significant results have been found with each of these methods and provide options for further study into short- and long-term mechanisms including Adenosine triphosphate (ATP)-sensitive potassium (KATP) channels, vesicular glutamate transporter (VGLUT), pannexin channels and adenosine receptors underlying ketogenic diet and other forms of metabolic therapy.
authors.affiliation: Department of Pharmacology, Jikei University School of Medicine Tokyo, Japan.
authors.forename: Masahito Jr
authors.initials: MJ
authors.lastname: Kawamura
authors.affiliation: Department of Psychology and Neuroscience Program, Trinity College Hartford, CT, USA.
authors.forename: David N
authors.initials: DN
authors.lastname: Ruskin
authors.affiliation: Department of Psychology and Neuroscience Program, Trinity College Hartford, CT, USA.
authors.forename: Susan A
authors.initials: SA
authors.lastname: Masino
keywords: ATP-sensitive potassium channels; adenosine receptors; ketone bodies; pannexin channels; temporal lobe epilepsy; vesicular glutamate transporter