BETA-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 P-hydroxybutyrate (PHB) on syn aptic transmission and morphological integrity during glucose deprivat ion in rat hippocampal slices. After the depression of excitatory post synaptic potentials (EPSPs) by 60 min of glucose deprivation, administ ration of 0.5-10 mM D-beta HB 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-beta HB to the media allowed robust long-term potentiation of EPSPs triggered by high frequency stimulation, and prevented the EP SP-spike facilitation that suggests hyperexcitability of neurons, Even after PND 15, D-beta HB blocked morphological changes produced by eit her glucose deprivation or glycolytic inhibition. These results indica te that D-beta HB is not only able to substitute for glucose as an ene rgy substrate but is also able to preserve neuronal integrity and stab ility, particularly during early development.