Age-related changes in composition of transcription factor, AP-1 complex in the rat brain.

We examined age-related changes in composition of transcription factor, activator protein-1 (AP-1) which binds to TPA responsive element (TRE) in the non-stimulated rat brain, using electrophoretic mobility-shift assay with immunodepletion/supershift assay. The total TRE-binding activity in the frontal cortex and the hippocampus of the aged rats markedly decreased to 66% and 43%, respectively, and TRE-bindings of AP-1 in both regions also decreased to 82% and 66%, respectively, with aging. Jun-Jun dimers accounted for approximately half of the total TRE-bindings and 80-90% of the AP-1 bindings, while there were fewer Fos-Jun dimers, in both examined regions of the non-stimulated adult. The proportion of active Fos-Jun heterodimers in the frontal cortex increased to up to half of the AP-1 bindings in the aged rats, indicating that cortical AP-1-related transcription may increase with aging even under the non-stimulated condition. In the hippocampus, inactive Jun-Jun homodimers became predominant in AP-1 with aging. This regional diversity of age-related changes in the composition of AP-1 in the brain may be related to changes or dysfunction in neuronal signal transduction in the aged.