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-I) which binds to TPA responsive element (TR E) in the non-stimulated rat brain, using electrophoretic mobility-shi ft assay with immunodepletion/supershift assay. The total TRE-binding activity in the frontal cortex and the hippocampus of the aged rats ma rkedly decreased to 66% and 43%, respectively, and TRE-bindings of AP- 1 in both regions also decreased to 82% and 66%, respectively, with ag ing. 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-J un dimers, in both examined regions of the non-stimulated adult. The p roportion of active Fos-Jun heterodimers in the frontal cortex increas ed to up to half of the AP-1 bindings in the aged rats, indicating tha t cortical AP-1-related transcription may increase with aging even und er the non-stimulated condition. In the hippocampus, inactive Jun-Jun homodimers became predominant in AP-1 with aging. This regional divers ity 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.