NURR1 MESSENGER-RNA EXPRESSION IN NEONATAL AND ADULT-RAT BRAIN FOLLOWING KAINIC ACID-INDUCED SEIZURE ACTIVITY

Nurr1 is an immediate early gene encoding a member of the steroid-thyr oid hormone receptor family. In PC12 cells, Nurr1 is readily induced b y membrane depolarization, but not by growth factors. Nurr1 is predomi nantly expressed in the brain, and is essential to the differentiation of midbrain dopaminergic neurons. However, Nurr1 is also expressed in brain regions unrelated to dopaminergic neurons, e.g., hippocampus an d cerebral cortex, and its immediate induction following seizure activ ity suggests a potential involvement of this transcription factor in m odulating gene expression in the nervous system. To investigate the re sponse of Nurr1 to neuronal activation, we analyzed Nurr1 mRNA express ion in neonatal and adult rat brain following kainic acid (KA)-induced seizure. In P7 animals, systemic injection of KA increased Nurr1 mRNA levels in a few hilar cells of the dentate gyrus and some pyramidal c ells of the CA3 region of the hippocampus. In older animals, Nurr1 ind uction progressively expanded to all hippocampal regions (P14, P21) an d eventually to cortical regions (adult). The increase was rapid and t ransient in the dentate gyrus, a structure resistant to the neurotoxic effect of KA, and was more prolonged in other regions more susceptibl e to KA toxicity. Induction of Nurr1 at early postnatal stages and rap id increase in the dentate gyrus following KA-induced seizure, suggest that Nurr1 expression is modulated by neuronal activity. On the other hand, prolonged Nurr1 induction in regions sensitive to KA toxicity i ndicates a possible involvement of Nurr1 in selective neuronal vulnera bility. (C) 1998 Elsevier Science B.V. All rights reserved.