Long-term expression of the 35,000 mol. wt fos-related antigen in rat brain after kainic acid treatment.

Systemic injection of kainic acid, a rigid analogue of glutamate, induces both the short-term and the long-term expression of activator protein-1 transcription factors. The short-term responses of activator protein-1 factors such as c-fos and fos-related antigens have been well studied. However, the long-term expression of activator protein-1 factor(s) induced by kainic acid is poorly understood. The present study was designed to document the long-term expression (up to seven months) of the fos-related antigens and to map their distributions in the rat brain after systemic treatment with kainic acid. A single dose of kainic acid (8 mg/kg) was injected i.p. into Fischer 344 rats and their epileptic seizure behaviour was monitored. The rats with full limbic seizures were chosen for long-term study. By using immunocytochemistry with an antibody that cross-reacts with all known fos-related antigens, western blot analysis and a gel mobility-shift assay, we have now shown that a 35,000 mol. wt fos-related antigen was induced by kainic acid treatment and expressed at high levels for up to five months. This fos-related antigen still maintains the activator protein-1 DNA binding activity in the rat brain seven months after kainic acid treatment. The fos-related antigens and activator protein-1 binding activity were continuously expressed at high levels throughout the experimental period in the dentate granule cells where mossy fibre collateral sprouting occurred after kainic acid treatment. Our results suggested that long-term expression of fos-related antigen may reflect the pathophysiological changes after kainic acid administration.