RAT NURR1 IS PROMINENTLY EXPRESSED IN PERIRHINAL CORTEX, AND DIFFERENTIALLY INDUCED IN THE HIPPOCAMPAL DENTATE GYRUS BY ELECTROCONVULSIVE VS, KINDLED SEIZURES

We isolated a rat orphan nuclear hormone receptor from a brain cortex cDNA library. The sequence of the cDNA insert was 2154 bp with an open reading frame of 1794 bp encoding a putative protein of 598 amino aci ds and predicted molecular mass of 65 kDa. The deduced amino acid sequ ence showed a strong homology to the mouse nurr1 and human NOT1 orphan nuclear hormone receptors of the NGFI-B/nur77/NAK1 gene subfamily. We refer to this rat clone as r-nurr1. Northern blot analysis showed tha t r-nurr1 mRNA was highly expressed in the brain and moderately in the lung as a 4.0 kb transcript. A smaller transcript of 2.5 kb was also detected in the testes. The level of r-nurr1 transcript in the heart, skeletal muscle, liver, kidney and spleen was marginal. In situ hybrid ization showed that r-nurr1 mRNA was constitutively expressed in vario us regions of the CNS, particularly in the deeper layers (TV to VI) of the perirhinal cortex and area 2 of parietal cortex. We further evalu ated the modulation of r-nurr1 expression in CNS by an electroconvulsi ve seizure (ECS) and by an amgydala-kindled seizure. A single ECS admi nistered via earclip electrodes induced a rapid and transient increase of r-nurr1 mRNA in the granule cells of the dentate gyrus, being sign ificant at 15 min after the seizure, maximal approximate to 1 h and ba ck to baseline at 4 h. The amygdala kindled seizure revealed a less ro bust and restricted nurr-1 induction in the CNS, as only two of the fo ur kindled animals showed a unilateral induction of nurr1 mRNA in the dentate gyms. These results suggest that r-nurr1 is an immediate-early gene that is differentially induced by ECS vs. kindled seizures. In a ddition, as r-nurr1 is prominently expressed in the specific brain sit es associated with memory acquisition and consolidation, it may play a role in memory processing.