Alterations in cerebral metabolism by the neurotoxin kainic acid studied by 13C MRS

Abstract

Kainic acid is a potent agonist at the kainate subclass of ionotropic glutamate receptors, and functional kainate receptors have not only been demonstrated on neurons but also on glial cells in culture. Kainic acid injections are used to induce limbic seizures in rodents. When combined with injections of [1‐13C]glucose and [1,2‐13C]acetate followed by analyses of forebrain extracts using 13C magnetic resonance spectroscopy (MRS) and HPLC information about glial neuronal interaction can be obtained. Using kainic acid treatment and 24 h later injection of 13C label a significant increase in label derived from [1,2‐13C]acetate was observed in glutamine and glutamate. Label derived from [1‐13C]glucose was unchanged in most metabolites, however, a decrease was observed in [2‐13C]GABA. It should be noted that only astrocytes are able to utilize acetate as a substrate, whereas acetyl CoA derived from glucose is metabolized predominantly in the neuronal tricarboxylic acid cycle. These results indicate that turnover of metabolites was increased predominantly in astrocytes whereas glutamatergic neurons were not affected. However, GABAergic neurons showed decreased GABA labelling, possibly due to reduced GABA release 24 h after kainic acid injection. Taken together with results obtained 2 weeks after kainic acid injection, it can be suggested that increased astrocytic activity one day after epileptic seizures results, subsequently, in an increased amino acid turnover in neurons. Cell culture work was also performed, results will be presented at the meeting.