Expression of zinc finger immediate early genes in rat brain after permanent middle cerebral artery occlusion.
The prolonged expression of the leucine zipper fos/jun immediate early genes (IEG) has been correlated with neuronal death after cerebral ischemia. In this study, the expression of six zinc finger IEG was examined using in situ hybridization in adult rats after middle cerebral artery occlusion (MCAO) with the suture model. NGFI-A, NGFI-B, NGFI-C, egr-2, egr-3, and Nurr1 mRNA were all induced throughout the ipsilateral cortex at 1 hour to 12 hours after MCAO. The cortical induction for most of the genes was greatest in the anterior cingulate and the anterior cerebral artery (ACA) and middle cerebral artery (MCA) transition zone. All of the zinc finger IEG were induced at 1 hour in all regions of hippocampus. NGFI-A and NGFI-B were induced in ipsilateral thalamus. Within areas of infarction, the basal IEG mRNA expression, and expression of the housekeeping gene cyclophilin A mRNA, decreased below control levels by 12 hours after the ischemia. Immediate early gene expression outside areas of infarction returned to control levels in most brain regions by 24 hours except for egr-3, which continued to be induced in the MCA/ ACA transition zone for 24 hours, and NGFI-A, which continued to be expressed in specific regions of the thalamus for 72 hours. The induction of these IEG in the cortex is likely caused by ischemia-induced cortical spreading depression, with the hippocampal and thalamic IEG induction being caused by activation of efferent cortical pathways to these regions. The prominent induction of NGFI-B, NGFI-C, egr-2, and egr-3 in the anterior cingulate cortex, the ACA/MCA transition zone, and medial striatum could reflect the ischemic regions around MCA infarcts. The prolonged NGFI-A expression observed in thalamus in this study, and in CA1 of hippocampus after global ischemia in the gerbil in a previous study, suggests that the prolonged NGFI-A, expression could be the result of or the cause of the delayed cell death. Prolonged NGFI-A expression, like c-fos and c-jun, seems to provide a marker for slowly dying neurons.
Honkaniemi
J
J
Department of Neurology, University of California at San Francisco, USA.
States
B A
BA
Weinstein
P R
PR
Espinoza
J
J
Sharp
F R
FR
D000591:Amino Acid Isomerases / Q000235:genetics; D000818:Animals; D002545:Brain Ischemia / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics; D002421:Caudate Nucleus / Q000737:chemistry; D002540:Cerebral Cortex / Q000737:chemistry; D004268:DNA-Binding Proteins / Q000032:analysis; D051766:Early Growth Response Protein 1; D051767:Early Growth Response Protein 2; D004706:Endodeoxyribonucleases / Q000235:genetics; D015870:Gene Expression; D016762:Genes, fos / Q000235:genetics; D016758:Genes, jun / Q000235:genetics; D006624:Hippocampus / Q000737:chemistry; D017874:Immediate-Early Proteins / Q000032:analysis*; D017403:In Situ Hybridization; D008969:Molecular Sequence Data; D019696:Peptidylprolyl Isomerase; D011699:Putamen / Q000737:chemistry; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D013788:Thalamus / Q000737:chemistry; D014157:Transcription Factors / Q000032:analysis; D014793:Visual Cortex / Q000737:chemistry; D016335:Zinc Fingers / Q000235:genetics*
D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D051766:Early Growth Response Protein 1; D051767:Early Growth Response Protein 2; C486110:Egr1 protein, rat; C497328:Egr2 protein, rat; D017874:Immediate-Early Proteins; D012333:RNA, Messenger; D014157:Transcription Factors; D004706:Endodeoxyribonucleases; D000591:Amino Acid Isomerases; D019696:Peptidylprolyl Isomerase