LEAD-INDUCED DEVELOPMENTAL-CHANGES IN AP-1 DNA-BINDING IN RAT-BRAIN

Exposure to lead during ontogeny is detrimental to the growth and deve lopment of the brain. Morphological abnormalities occur in the develop ing brain, which are manifested as mental retardation and other neurol ogical disorders. Despite extensive research. the biochemical mechanis m for neurological effects of lead has not been established but appear s to be al the level of the genome since aberrant expression of develo pmentally-important genes has been reported. Basal levels of activator protein 1 (AP-1) transcription factor DNA binding are elevated in the rat brain during the early postnatal period. The AP-1 DNA binding com plex is composed of a Jun:cAMP responsive element binding protein dime r, which appears to modulate expression of developmentally-important g enes that contain AP-1 binding sites in their promoter. Brain regions from perinatally lead-exposed rats were examined on postnatal days 3, 9 and 15 for DNA binding activity to the AP-1 DNA sequence. AP-1 DNA b inding activities were significantly increased on postnatal day 3 in h ippocampus and cortex from lead-treated rats with no other area (front al lobe or brainstem) or timepoint showing significant changes. Since no increases were detected in the level of Jun protein which is a comp onent of the AP-1 binding complex, post-translational modification may be involved in enhancing DNA binding activity. By altering levels of AP-1 DNA binding to the promoter regions, lead exposure may be changin g the levels of mRNA synthesis of developmentally important genes. (C) 1997 ISDN.