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

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Abstract
Objective: To determine the effect of the ketone bodies β-hydroxybutyrate (βHB) 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 βHB 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 hippocampal-entorhinal cortex slice model. Results: βHB 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.