Sustained potentiation of AP1 DNA binding is not always associated with neuronal death following systemic administration of kainic acid in murine hippocampus.
Mice were intraperitoneally injected with kainic acid (KA), followed by dissection of frozen coronal sections and subsequent punching out of the pyramidal and granular cell layers in the hippocampus under a binocular microscope. Systemic administration of KA resulted in marked and sustained potentiation of binding of a radiolabeled double stranded oligonucleotide probe for the nuclear transcription factor activator protein-1 (AP1) in the pyramidal cell layers of the CA1 and CA3 subfields and the granule cell layers of the dentate gyrus 2-18 h later. Morphological evaluation using cresyl violet revealed marked losses of neuronal layers in the pyramidal CA1 and CA3 subfields, but not in the granular dentate gyrus, within 6 weeks after administration. Supershift analysis using antibodies against different Jun and Fos family members differentiated between AP1 DNA binding in hippocampal nuclear extracts obtained 2 and 18 h after the administration of KA. These results suggest that neuronal death may not always follow modulation of de novo synthesis of particular proteins through sustained potentiation of AP1 DNA binding which involves expression of different Jun and Fos family members in response to systemic administration of KA in murine hippocampus.
Kitayama
T
T
Department of Pharmacology, Setsunan University, Hirakata, Osaka, Japan.
Ogita
K
K
Yoneda
Y
Y
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D004247:DNA / Q000378:metabolism*; D018891:Dentate Gyrus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D019281:Dimerization; D016762:Genes, fos; D016758:Genes, jun; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D007274:Injections, Intraperitoneal; D007608:Kainic Acid / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D005810:Multigene Family; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000378:metabolism*; D009498:Neurotoxins / Q000008:administration & dosage / Q000494:pharmacology*; D011485:Protein Binding / Q000187:drug effects; D016760:Proto-Oncogene Proteins c-fos / Q000737:chemistry / Q000378:metabolism*; D016755:Proto-Oncogene Proteins c-jun / Q000737:chemistry / Q000378:metabolism*; D017966:Pyramidal Cells / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D013268:Stimulation, Chemical; D018808:Transcription Factor AP-1 / Q000737:chemistry / Q000378:metabolism*
D009419:Nerve Tissue Proteins; D009498:Neurotoxins; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D018808:Transcription Factor AP-1; D004247:DNA; D007608:Kainic Acid