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

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  • 1. Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
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    • Izumi Y 1
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The Journal of Clinical Investigation, 01 Mar 1998, 101(5):1121-1132
https://doi.org/10.1172/jci1009 PMID: 9486983 PMCID: PMC508664

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Abstract 

To determine whether ketone bodies sustain neuronal function as energy substrates, we examined the effects of beta-hydroxybutyrate (betaHB) 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-betaHB 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-betaHB 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-betaHB blocked morphological changes produced by either glucose deprivation or glycolytic inhibition. These results indicate that D-betaHB 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.

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Logo of jcinvestThe Journal of Clinical Investigation
J Clin Invest. 1998 Mar 1; 101(5): 1121–1132.
PMCID: PMC508664
PMID: 9486983

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

Y Izumi, K Ishii, H Katsuki, A M Benz, and C F Zorumski
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Abstract

To determine whether ketone bodies sustain neuronal function as energy substrates, we examined the effects of beta-hydroxybutyrate (betaHB) 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-betaHB 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-betaHB 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-betaHB blocked morphological changes produced by either glucose deprivation or glycolytic inhibition. These results indicate that D-betaHB 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.

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Selected References

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