GABA A receptor subunits in the rat hippocampus II: Altered distribution in kainic acid-induced temporal lobe epilepsy

Abstract

Intraperitoneal injection of kainic acid in the rat represents a widely used animal model of human temporal lobe epilepsy. Injection of kainic acid induces acute limbic seizures which are accompanied by seizure-induced brain damage and late spontaneous recurrent seizures. There is considerable evidence for an altered transmission of GABA in human temporal lobe epilepsy and in the kainic acid model. We therefore investigated by immunocytochemistry the distribution of 13 GABA receptor subunits in the hippocampus of rats 12 h, 24 h, and two, seven and 30 days after injection of kainic acid. Within the molecular layer of the dentate gyrus, decreases in α 2- and δ- and slight increases in α 1-, β 2- and β 3-immunoreactivities were observed at early intervals (12 to 24 h) after kainic acid injection. These changes were succeeded by marked increases in α 1-, α 2-, α 4-, α 5-, β 1-, β 3-, γ 2- and δ-immunoreactivities in the same area after seven to 30 days. Within the hippocampus proper, changes in expression of GABA A receptor subunits were demarcated by considerable neurodegeneration of CA1 and CA3 pyramidal neurons. All subunits present within dendritic areas of CA1 and CA3 were affected. These were α 1, α 2, α 5, β 1– β 3, γ 2 and α 4 (present only in CA1). Decreases in these subunits were followed by increased expression of α 2-, α 5-, β 3-, γ 2- and δ-subunits in the hippocampus proper notably in CA3 at later intervals (up to 30 days). α 1-, β 2-, γ 2- and δ-subunits were found in presumed GABA containing interneurons throughout the hippocampus. Their immunoreactivity was augmented after two to seven days. Some α 4-, γ 3- and δ-immunoreactivity was also found in astrocytes 48 h after kainic acid injection. Our data indicate an impairment of GABA-mediated neurotransmission due to a lasting loss of GABA A receptor containing cells after kainic acid-induced seizures. The seizure-induced loss in GABA A receptors within the hippocampus may in part be compensated by increased expression of GABA A receptor subunits within the molecular layer of the dentate gyrus and in pyramidal cells.