1. ¹Department of Neuroscience, Norwegian University of Science and Technology (NTNU), Trondheim, Norway
2. ²INSERM 666, Université Louis Pasteur, Strasbourg, France

Correspondence: Professor U Sonnewald, Department of Neuroscience, Faculty of Medicine, NTNU, Olav Kyrres gate. 3, N-7489 Trondheim, Norway. E-mail: Ursula.Sonnewald@ntnu.no

Received 20 December 2004; Revised 7 February 2005; Accepted 14 February 2005; Published online 18 May 2005.

Abstract

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 [1-¹³C]glucose, a substrate for neurons and astrocytes, and [1,2-¹³C]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 ¹³C and ¹H 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 [1,2-¹³C]acetate was similar in control and epileptic rats, indicating normal astrocytic metabolism. However, labeling of glutamate, GABA, aspartate, and alanine from [1-¹³C]glucose was decreased in all areas possibly reflecting neuronal loss. The labeling of glutamine from [1-¹³C]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.