Nurr1 mRNA 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-thyroid hormone receptor family. In PC12 cells, Nurr1 is readily induced by membrane depolarization, but not by growth factors. Nurr1 is predominantly 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 and cerebral cortex, and its immediate induction following seizure activity suggests a potential involvement of this transcription factor in modulating gene expression in the nervous system. To investigate the response of Nurr1 to neuronal activation, we analyzed Nurr1 mRNA expression 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 cells of the CA3 region of the hippocampus. In older animals, Nurr1 induction progressively expanded to all hippocampal regions (P14, P21) and eventually to cortical regions (adult). The increase was rapid and transient in the dentate gyrus, a structure resistant to the neurotoxic effect of KA, and was more prolonged in other regions more susceptible to KA toxicity. Induction of Nurr1 at early postnatal stages and rapid 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 indicates a possible involvement of Nurr1 in selective neuronal vulnerability.
Crispino
M
M
Neuroscience Program, Hedco Neuroscience Building, Room 311, University of Southern California, Los Angeles, CA 90089-2520, USA. crispino@rana.usc.edu
Tocco
G
G
Feldman
J D
JD
Herschman
H R
HR
Baudry
M
M
D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D001923:Brain Chemistry / Q000502:physiology*; D004268:DNA-Binding Proteins; D004827:Epilepsy / Q000503:physiopathology*; D018690:Excitatory Amino Acid Agonists; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D017403:In Situ Hybridization; D007608:Kainic Acid; D008297:Male; D009419:Nerve Tissue Proteins / Q000235:genetics; D057126:Nuclear Receptor Subfamily 4, Group A, Member 2; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D013569:Synapses / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics*
D004268:DNA-Binding Proteins; D018690:Excitatory Amino Acid Agonists; D009419:Nerve Tissue Proteins; C539884:Nr4a2 protein, rat; D057126:Nuclear Receptor Subfamily 4, Group A, Member 2; D012333:RNA, Messenger; D014157:Transcription Factors; D007608:Kainic Acid