Metabolism is normal in astrocytes in chronically epileptic rats:: a 13C NMR study of neuronal-glial interactions in a model of temporal lobe epilepsy

The aim of the present work was to study potential disturbances in metabolism and interactions between neurons and glia in the lithium-pilocarpine model of temporal lobe epilepsy. Rats chronically epileptic for 1 month received [1-C-13]glucose, a substrate for neurons and astrocytes, and [1,2-C-13]acetate, a substrate for astrocytes only. Analyses of extracts from cerebral cortex, cerebellum, and hippocampal formation (hippocampus, amygdala, entorhinal, and piriform cortices) were performed using C-13 and H-1 nuclear magnetic resonance spectroscopy and HPLC. In the hippocampal formation of epileptic rats, levels of glutamate, aspartate, N-acetyl aspartate, adenosine triphosphate plus adenosine diphosphate and glutathione were decreased. In all regions studied, labeling from [1,2-C-13]acetate was similar in control and epileptic rats, indicating normal astrocytic metabolism. However, labeling of glutamate, GABA, aspartate, and alanine from [1-C-13]glucose was decreased in all areas possibly reflecting neuronal loss. The labeling of glutamine from [1-C-13]glucose was decreased in cerebral cortex and cerebellum and unchanged in hippocampal formation. In conclusion, no changes were detected in glial-neuronal interactions in the hippocampal formation while in cortex and cerebellum the flow of glutamate to astrocytes was decreased, indicating a disturbed glutamate-glutamine cycle. This is, to our knowledge, the first study showing that metabolic disturbances are confined to neurons inside the epileptic circuit.