Time-dependent effect of kainate-induced seizures on glutamate receptor GluR5, GluR6, and GluR7 mRNA and Protein Expression in rat hippocampus

Abstract

Purpose: Glutamate receptor 6 is strongly implicated in human refractory epilepsy and in kainic acid (KA)-induced status epilepticus (SE). In vitro pharmacologic studies with newer antiepileptic drugs (AEDs) are increasingly indicating the role of glutamate receptor 5 (GluR5) in epilepsy. Glutamate receptor 7 (GluR7) has been the least investigated in the context of epilepsy. We studied the messenger ribonucleic acid (mRNA) and protein expression of GluR5, GluR6, and GluR7 in rat hippocampus 72 h, 90 days, and 180 days after KA-induced SE.

Methods: SE was induced by injecting KA intraperitoneally (i.p.) into adult rats. The hippocampi were isolated 72 h, 90 days, and 180 days after SE. Reverse transcription-polymerase chain reaction (RT-PCR) was performed for mRNA expression. Western blots determined the protein expression.

Results: A significant increase was noted in GluR5 expression in KA-treated animals compared with controls at 72 h and 180 days, with no significant difference at the intervening 90-day point. Protein levels for GluR5 increased at 72 h and remained elevated until 180 days. GluR7 mRNA showed a significant decrease at 90 days after seizures. Neither the mRNA expression nor the protein levels of GluR6 differed from controls at any of the times after SE.

Conclusions: KA-induced SE leads to an upregulation of GluR5 mRNA and protein and a downregulation of GluR7 mRNA in rat hippocampus, with no change in GluR6 mRNA or protein expression.