Expression of AP-1 transcription factors in rat hippocampus and cerebellum after trimethyltin neurotoxicity

Neurotoxic insult causes neurons to degenerate due to necrosis or apoptosis. After this neurodegenerative phase, gene expression in surviving neurons is altered to undergo regeneration and repair to adapt to changes in the cellular environment. In this study, we examined the expression of four AP-1 transcription factors, Jun, JunB, JunD and FRA-2, and AP-1 DNA binding activity in the rat hippocampus to examine changes during the periods of degeneration and then of regeneration and repair after TMT-induced neurotoxicity. The expression of these factors in the cerebellum was examined as a control since this brain region is not grossly affected by TMT. AP-1 DNA binding slowly increased in both the cerebellum and hippocampus from one hour to eight days after TMT exposure. Levels of Jun in the hippocampus significantly increased at 12 hours after TMT while JunB and JunD expression did not change. On the otherhand, FRA-2 was induced at 8 days in the hippocampus after TMT treatment and was expressed only in hippocampi containing neurodegeneration as gauged by elevated glial fibrillary acidic protein levels. FRA-2 immunoreactivity was detected in the AP-1 DNA binding complex only in hippocampal extracts from rats after eight days post- trimethyltin administration. Thus, FRA-2 is a component of the AP-1 DNA binding complex suggesting that it is involved in regulating genes during a later stage of TMT neurotoxicity.