CONTRASTING EFFECTS OF ELECTROCONVULSIVE SHOCK ON MESSENGER-RNAS ENCODING THE HIGH-AFFINITY KAINATE RECEPTOR SUBUNITS (KA1 AND KA2) AND CYCLOPHILIN IN THE RAT

Kainate-preferring glutamate receptors may contribute to the glutamate rgic responses to seizures. The cloning of their encoding genes overco mes limitations of the receptor ligands available for their investigat ion. We have examined the expression of the high affinity kainate rece ptor subunits KA1 and KA2 mRNAs in the rat hippocampus, using electroc onvulsive shock (ECS) as a seizure paradigm not confounded by neurotox icity. A single shock reduced the levels of KA1 mRNA in the CA3c regio n, while increasing the expression of KA2 mRNA in the dentate gyrus. F ollowing repeated ECS (5 shocks over 10 days), KA1 mRNA was reduced in CA3c and in CA3a-b but was unchanged in dentate gyrus. KA2 mRNA, on t he other hand, significantly increased in dentate gyrus, and to a less er extent in CA3c and CA1. All changes in KA1 and KA2 mRNAs had return ed to baseline 3 weeks after the last shock. We also measured the expr ession of cyclophilin mRNA, and found it to be reduced in all hippocam pal subfields, and in the parietal cortex, after a single ECS. It retu rned to control levels after repeated ECS but was again reduced follow ing 3 weeks recovery from repeated ECS. These results indicate that th e expression of KA1 and KA2 not only change in opposite directions in the rat hippocampus after ECS, but that the alterations are anatomical ly and temporally regulated. In the respect that cyclophilin is regard ed as a housekeeping gene, the reduction in its mRNA suggests that ECS may have more persistent and widespread effects on brain gene express ion than previously suspected.