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Preparation of Acute Hippocampal Slices from Rats and Transgenic Mice for the Study of Synaptic Alterations during Aging and Amyloid Pathology
Published on: March 23, 2011
beta-Hydroxybutyrate fuels synaptic function during development. Histological and physiological evidence in rat
1Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri 63110, USA. izumiy@psychiatry.wustl.edu
The Journal of Clinical Investigation
|April 16, 1998
Summary
Ketone bodies like beta-hydroxybutyrate (betaHB) can sustain brain energy needs and protect neurons. D-betaHB specifically supports synaptic function and neuronal integrity in developing rat brains during glucose deprivation.
Area of Science:
- Neuroscience
- Metabolism
- Developmental Biology
Background:
- Glucose is the primary energy substrate for neurons.
- Neuronal function depends on a continuous energy supply.
- Ketone bodies are an alternative fuel source.
Purpose of the Study:
- To investigate if ketone bodies can serve as energy substrates for neuronal function.
- To examine the effects of beta-hydroxybutyrate (betaHB) on synaptic transmission and neuronal integrity during glucose deprivation.
- To determine the developmental relevance of betaHB's neuroprotective effects.
Main Methods:
- Rat hippocampal slices from different postnatal days (PND 15, 30, 120) were used.
- Glucose deprivation was induced to mimic energy deficit.
- Effects of D-beta-hydroxybutyrate (D-betaHB) on excitatory postsynaptic potentials (EPSPs) and neuronal morphology were assessed.
- Long-term potentiation (LTP) and EPSP-spike facilitation were measured.
Main Results:
- D-betaHB (0.5-10 mM) restored synaptic transmission (EPSPs) in PND 15 rat hippocampal slices after glucose deprivation.
- This restoration was not observed in slices from older rats (PND 30, 120).
- At PND 15, D-betaHB supported robust long-term potentiation and prevented neuronal hyperexcitability.
- D-betaHB also protected against morphological damage caused by glucose deprivation or glycolytic inhibition.
Conclusions:
- D-betaHB can substitute for glucose as an energy substrate in the developing brain.
- D-betaHB preserves neuronal integrity and stability, particularly during early development.
- These findings highlight the potential role of ketone bodies in supporting brain function during periods of limited glucose availability.
