Ketone bodies do not directly alter excitatory or inhibitory hippocampal synaptic transmission

Objective: To determine the effect of the ketone bodies beta-hydroxybutyrate (beta HB) and acetoacetate (AA) on excitatory and inhibitory neurotransmission in the mammalian CNS. Background: The ketogenic diet is presumed to be an effective anticonvulsant regimen for some children with medically intractable seizures. However, its mechanism of action remains a mystery. According to one hypothesis, ketone bodies have anticonvulsant properties. Methods: The authors examined the effect of beta HB and AA on excitatory and inhibitory synaptic transmission in rat hippocampal entorhinal cortex slices and cultured hippocampal neurons. In cultured neurons, their effect was also directly assayed on postsynaptic receptor properties. Finally, their ability to prevent spontaneous seizures was determined in a hippocampalentorhinal cortex slice model. Results: beta HB and AA did not alter synaptic transmission in these models. Conclusions: The anticonvulsant properties of the ketogenic diet do not result from a direct effect of ketone bodies on the primary voltage and ligand gated ion channels mediating excitatory or inhibitory neurotransmission in the hippocampus.