Amino acid neurotransmitter metabolism in neurones and glia following kainate injection in rats

Abstract

Limbic seizure was induced in rats by intraperitoneal injection of the glutamate receptor agonist kainic acid. After 14 days [1– 13C]glucose and [1,2– 13C]acetate were injected subcutaneously and the rats killed 15 min later. Analysis of brain extracts was performed using 13C-magnetic resonance spectroscopy and high performance liquid chromatography. No significant differences between the two groups of rats were found for label concentration in blood or total metabolite tissue levels. Only astrocytes are able to utilize acetate as a substrate, whereas glucose is thought to be metabolized predominantly in the neuronal tricarboxylic acid cycle. Thus information about neuronal and astrocytic metabolism could be obtained in the same animal. A significant increase in label derived from [1– 13C]glucose was observed in metabolites such as glutamate, γ-aminobutyric acid, aspartate, and succinate (all of which are mainly labelled in neurones). The increased labelling of glutamine in epileptic rats might be due to transfer of labelled glutamate from neurones to astrocytes. Astrocytic metabolism of acetate and transfer of glutamine to neurones were not affected. The results suggest that increased neuronal activity 2 weeks following epileptic seizures produces increased amino acid turnover in neurones. Changes in astrocytic metabolism were not detected.