1. ¹Department of Neuroscience, Norwegian University of Science and Technology (NTNU), Trondheim, Norway
2. ²INSERM U433, Lyon, France
3. ³INSERM U666, Faculty of Medicine, Strasbourg, France

Correspondence: Dr A Nehlig, INSERM U666, Faculty of Medicine, 11 Rue Humann, 67085 Strasbourg Cedex, France. E-mail: nehlig@neurochem.u-strasbg.fr

Received 10 January 2005; Revised 24 December 2005; Accepted 30 January 2006; Published online 15 March 2006.

Abstract

Disturbances in GABAergic and glutamatergic neurotransmission in the thalamocortical loop are involved in absence seizures. Here, we examined potential disturbances in metabolism and interactions between neurons and glia in 5-month-old genetic absence epilepsy rats from Strasbourg (GAERS) and nonepileptic rats (NER). Animals received [1-¹³C]glucose and [1,2-¹³C]acetate, the preferential substrates of neurons and astrocytes, respectively. Extracts from cerebral cortex, thalamus, and hippocampus were analyzed by ¹³C nuclear magnetic resonance spectroscopy. Most changes were detected in the cortex. Pyruvate metabolism was enhanced as evidenced by increases of lactate, and labeled and unlabeled alanine. Neuronal mitochondrial metabolism was also enhanced as detected by elevated amounts of N-acetylaspartate and nicotinamide adenine dinucleotide as well as increased incorporation of label from [2-¹³C]acetyl CoA into glutamate, glutamine, and aspartate. Likewise, mitochondrial metabolism in astrocytes was increased. Changes in thalamus were restricted to increased concentration and labeling of glutamine. Changes in the hippocampus were similar to those in the cortex. This increase in glutamate–glutamine metabolism in cortical neurons and astrocytes accompanied by a decreased gamma aminobyturic acid level may lead to impaired thalamic filter function. Hence, reduced sensory input to cortex could allow the occurrence of spike-and-wave discharges in the thalamocortical loop. Increased glutamatergic output from the cortex to hippocampus may be the underlying cause of improved learning in GAERS.