Brain libraries indicate differential RNA expression in schizophrenia and bipolar disease

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In eukaryotes, de novo synthesis of proteins is mainly under control at the level of gene transcription by nuclear transcription factors with unique protein motifs such as leucine-zipper and zinc-finger. Binding of radiolabeled oligonucleotide probes for the “leucine-zipper” transcription factors, including activator protein-1 (AP1) and cyclic AMP response element binding protein (CREB), was markedly reduced in nuclear extracts of the adrenals from mice sacrificed 2 h after the subcutaneous injection of triamcinolone acetonide (TA), and agonist at glucocorticoid (GC) receptors which are also a transcription factor with “zinc-finger” motifs. The reduction was most significant 2 h after the administration, with recovery to the control level within 7 h after the injection. Moreover, the administration of TA invariably doubled immunoreactivities to an antibody against human GC receptors in nuclear fractions of the adrenal, pituitary and hypothalamus, with a concomitant reduction of those in cytosol fractions. Similar inhibition by TA was also seen with AP1 binding in the pituitary, while TA did not affect binding of radioprobes for AP1 and CREB in any discrete brain structures. These results suggest that systemic TA signals may be preferentially transduced into cell nuclei to attenuate DNA binding activities of AP1 through molecular mechanisms associated with crosstalk between transcription factors with different proteins motifs in murine peripheral but not central excitable tissues.