Expression of AP-1 transcription factors in rat hippocampus and cerebellumafter 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 ce llular 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 acti vity in the rat hippocampus to examine changes during the periods of degene ration 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 Drain region is not grossly affected by TMT. AP-1 DNA binding s lowly increased in both the cerebellum and hippocampus from one hour to eig ht days after TMT exposure. Levels of Jun in the hippocampus significantly increased at 12 hours after TMT while JunB and JunD expression did not chan ge. On the otherhand, FRA-2 was induced at 8 days in the hippocampus after TMT treatment and was expressed only in hippocampi containing neurodegenera tion as gauged by elevated glial fibrillary acidic protein levels. FRA-2 im munoreactivity was detected in the AP-1 DNA binding complex only in hippoca mpal 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 neurotoxicit y. (C) 1999 Intox Press, Inc.