title: Ketone bodies attenuate excitotoxic cell injury in the rat hippocampal slice under conditions of reduced glucose availability.
abstract: Calorie restriction and the ketogenic diet have been successfully used in models of neuroprotection. However, there are limitations in clinical application of these diets and attention has turned to understanding their mechanism of action. Ketone bodies are produced in both diets and maybe involved in their ability to attenuate neuronal injury. This study seeks to assess the effects of ketone bodies on neuronal transmission and their efficacy in reducing the impact of known excitotoxins. We made use of extracellular recordings from rat hippocampal slices and demonstrate that ketone bodies had no effect on neuronal transmission or induction of long-term potentiation (LTP). Perfusion of slices with N-methyl-d-aspartate (NMDA, 15 μM) produced neuronal depression suggestive of cell injury (antidromic recording also demonstrated similar depression), such that recovery of population spike potentials after 60 minutes was 27% in normal (10 mM) glucose but only 7% during reduced (2·5 mM) glucose availability. Experiments in ketone bodies demonstrated improved recovery (31%) but only under conditions of low glucose. Similarly, there was enhanced recovery of slices treated with kainic acid (KA, 30 μM) in reduced glucose media (13-27%), but no difference in normal glucose. These findings suggest that ketone bodies do not alter neuronal function but can alter the response to excitotoxins when energy supplies are impaired, probably by acting as an alternative energy substrate.
authors.forename: Farid F
authors.initials: FF
authors.lastname: Youssef
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity; D005947:Glucose / Q000172:deficiency*; D006624:Hippocampus / Q000187:drug effects* / Q000503:physiopathology*; D007608:Kainic Acid / Q000633:toxicity; D007657:Ketone Bodies / Q000378:metabolism*; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology; D008297:Male; D008839:Microelectrodes; D016202:N-Methylaspartate / Q000633:toxicity; D017207:Rats, Sprague-Dawley; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D046509:Tissue Culture Techniques
chemical_list: D018690:Excitatory Amino Acid Agonists; D007657:Ketone Bodies; D016202:N-Methylaspartate; D005947:Glucose; D007608:Kainic Acid
keywords: Acetoacetate,; Beta-hydroxybutyrate,; Kainic acid,; Long-term potentiation,; NMDA