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Abstract

Fasting and carbohydrate restricted diets have been a historic and treatment for epilepsy, although the mechanism of action is not known. We report that reducing glucose utilization in brain slices by replacing glucose in the external medium with lactate or pyruvate or chemically inhibiting glycolysis reduces synchronized epileptiform bursting in hippocampal slices by 30 to to 90%. The antiepileptic effect of inhibiting glycose utiliaztion can be prevented by 3-MCP, a specific inhibitor of the gluconeogenic enzyme phosphoenolpyruvate carboxykinase (PEPCK). Substrates for PEPCK, oxaloacetate, glycolic acid, b-chlorolactate and thioglycolate reduce epileptiform bursting by 20 to 50% in the presence of normal extracellular glucose concentration. Application of 3-MCP, PEPCK or 5mM phophoenolpyruvate (PEP) to brain slices in normal ACSF with 10 mM glucose more than doubles the frequency of epileptiform bursting. This suggests that there is basal rate of flux oxaloacetat through PEPCK in the brain, and this flux can regulate epileptform bursting, possibly by altering the GTP to GDP ratio at synaptic terminals





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Would you like to learn more about my day job studing epilepsy and how the gluconeogenic enzyme PEPCK is the mechanism of action for the Ketogenic Diet, 2-DG (2-deoxy-d-glucose or 2-deoxyglucose)?

Steve Kriegler Photographs

Steve's model for the Ketogenic Diet as a treatment for epilepsy, as well as the mechanism of action for 2-deoxyglucose (2-DG)

Tom Sutula, Avtar Roopra investigated by the UW for plagiarism

GTP dynamin endocytosis epilepsy 2-deoxy-D-glucose (2-Deoxyglucose or 2-DG)


Prints of Steve Kriegler’s photographs are now available at ImageKind