Prolonged expression of AP-1 transcription factors in the rat hippocampus after systemic kainate treatment.
Systemic administration of kainate, a glutamate receptor agonist, caused neuronal death in the CA1 and CA3 fields of the rat hippocampus. In the areas of cell loss, reactive astrocytes increased their expression of an astrocyte-specific protein, glial fibrillary acidic protein (GFAP). AP-1 DNA binding activity and the expression of a 35 kDa fos-related antigen (fra) remained elevated in the rat hippocampus for at least 2 weeks after a single systemic injection of kainate, which correlated with changes in gene expression during reactive gliosis. Immunoreactivity for fras was detected in the nuclei of neurons in the dentate gyrus, but relatively few cells in CA1 and CA3 were immunoreactive 1 week after kainate treatment. However, elevated AP-1 DNA binding activity was observed in the CA1 and CA3 regions as well as in the dentate gyrus, suggesting that proteins other than the fras were involved in the astrocytic AP-1 complex. The AP-1 DNA binding activity in hippocampus recognized an AP-1 sequence from the promoter region of the GFAP gene, suggesting that GFAP is a potential target gene. Thus, a single systemic injection of kainate causes long-term activation of AP-1 DNA binding activity in the rat hippocampus and may be important for long-term changes in gene expression in hippocampal cells.
Neuropharmacology Section, National Institute of Environmental Health Sciences, National Institute of Health, Research Triangle Park, North Carolina 27709.
K R
KR
Pennypacker
L
L
Thai
J S
JS
Hong
M K
MK
McMillian
D000818:Animals; D001483:Base Sequence; D015153:Blotting, Western; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics / Q000378:metabolism; D005911:Gliosis / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D018398:Homeodomain Proteins; D007150:Immunohistochemistry; D007608:Kainic Acid / Q000494:pharmacology*; D008297:Male; D015778:Minor Histocompatibility Antigens; D008969:Molecular Sequence Data; D015345:Oligonucleotide Probes / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2; D051381:Rats; D011916:Rats, Inbred F344; D051818:Replication Protein C; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors / Q000378:metabolism*
C096816:BCL2-related protein A1; D004268:DNA-Binding Proteins; D005904:Glial Fibrillary Acidic Protein; D018398:Homeodomain Proteins; C096063:MATA1 protein, S cerevisiae; D015778:Minor Histocompatibility Antigens; D015345:Oligonucleotide Probes; D019253:Proto-Oncogene Proteins c-bcl-2; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D004247:DNA; D051818:Replication Protein C; D007608:Kainic Acid