Prolonged expression of zinc finger immediate-early gene mRNAs and decreased protein synthesis following kainic acid induced seizures.
In the present study in situ hybridization was used to study the effect of kainic acid induced seizures on the expression of the zinc finger immediate-early genes (IEGs) NGFI-A, NGFI-B, NGFI-C, egr-2; egr-3 and Nurr1. Kainic acid markedly induced these IEGs especially in hippocampus, cortex and amygdala by 30 min. This induction gradually decreased and returned to baseline by 24 h in most regions. However, in the CA1 and CA3 subfields of hippocampus known to be damaged by kainic acid the expression of all the IEGs except egr-2 remained elevated for 24 h. NGFI-A, NGFI-B, NGFI-C and to a lesser extent, Nurr1, remained elevated also in the subcortical region of the temporal lobe. By 24 h incorporation of 14C-leucine decreased in the piriform cortex, amygdala, and in the CA1 and CA3 subfields, but not in CA2 and dentate gyrus. These areas showing decreased protein synthesis in the hippocampus by 24 h showed prolonged IEG induction, whereas IEG expression returned to control levels in areas showing normal protein synthesis. In the temporal lobe decreased protein synthesis coexisted with decreased IEG expression, whereas areas in the vicinity of the region showing decreased protein synthesis demonstrated elevated IEG expression. The decreased protein synthesis was localized in areas where extensive neuronal death has occurred. This prolonged IEG induction in the hippocampus, which has been linked with neuronal death, could solely represent a prolonged mRNA turnover caused by disrupted protein synthesis. The prolonged IEG expression in the temporal lobe appeared to be localized in regions where the cells are in stress, but still viable. The sustained IEG expression might therefore either represent a stress response by which the neurons are trying to protect themselves or, alternatively, the IEG response may be an early sign indicating that these cells are initiating a pathway leading to programmed cell death.
Honkaniemi
J
J
Department of Neurology, University of California at San Francisco, USA. bljaho@kielo.uta.fi
Sharp
F R
FR
D000679:Amygdala / Q000737:chemistry / Q000166:cytology; D000818:Animals; D002540:Cerebral Cortex / Q000737:chemistry / Q000166:cytology; D004268:DNA-Binding Proteins / Q000235:genetics; D018891:Dentate Gyrus / Q000737:chemistry / Q000166:cytology; D051766:Early Growth Response Protein 1; D051767:Early Growth Response Protein 2; D051776:Early Growth Response Protein 3; D004827:Epilepsy / Q000139:chemically induced / Q000503:physiopathology*; D018690:Excitatory Amino Acid Agonists; D005786:Gene Expression Regulation / Q000502:physiology; D017781:Genes, Immediate-Early / Q000235:genetics*; D018698:Glutamic Acid / Q000378:metabolism; D017874:Immediate-Early Proteins; D017403:In Situ Hybridization; D007608:Kainic Acid; D008297:Male; D009419:Nerve Tissue Proteins / Q000235:genetics; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1; D057126:Nuclear Receptor Subfamily 4, Group A, Member 2; D015345:Oligonucleotide Probes; D017966:Pyramidal Cells / Q000737:chemistry / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018160:Receptors, Cytoplasmic and Nuclear; D011987:Receptors, Steroid; D014157:Transcription Factors / Q000235:genetics; D016335:Zinc Fingers / Q000235:genetics*