β-Hydroxybutyrate fuels synaptic function during development. Histological and physiological evidence in rat hippocampal slices

To determine whether ketone bodies sustain neuronal function as energy substrates, we examined the effects of β-hydroxybutyrate (βHB) on synaptic transmission and morphological integrity during glucose deprivation in rat hippocampal slices. After the depression of excitatory postsynaptic potentials (EPSPs) by 60 min of glucose deprivation, administration of 0.5- 10 mM D-βHB restored EPSPs in slices from postnatal day (PND) 15 rats but not in slices from PND 30 or 120 rats. At PND 15, adding D-βHB to the media allowed robust long-term potentiation of EPSPs triggered by high frequency stimulation, and prevented the EPSP-spike facilitation that suggests hyperexcitability of neurons. Even after PND 15, D-βHB blocked morphological changes produced by either glucose deprivation or glycolytic inhibition. These results indicate that D-βHB is not only able to substitute for glucose as an energy substrate but is also able to preserve neuronal integrity and stability, particularly during early development.