Inhibition of histone deacetylation by trichostatin A intensifies the transcriptions of neuronal c-fos and c-jun genes after kainate stimulation.

Kainate stimulation induces the expression of immediate early genes, c-fos and c-jun genes. Trichostatin A (TSA), a potent histone deacetylase (HDAC) enzyme inhibitor was used to test the role of histone hyperacetylation in the transcriptional regulation of c-fos and c-jun genes in neuronal cells in vivo and in vitro. Intraperitoneal administration of TSA increased histone H4 acetylation in hippocampi. Mice pretreatment with TSA were injected with kainic acid intraperitoneally and sacrificed over a time course of 12 h. Northern blot analysis and in situ hybridization showed that TSA pretreatment caused an increase in pre-existing basal levels of c-jun at 0 h and also intensified the maximal expression of both genes especially in the pyramidal layers of the hippocampus, thus demonstrating the inhibition of HDACs subsequently led to histone hyperacetylation to increase these genes expressions. TSA did not prolong the expression of c-fos or c-jun gene, in contrary to what we expected. Primary hippocampal neuron cell culture also displayed a similar pattern of c-fos and c-jun mRNA enhancement with trichostatin A pretreatment. This study demonstrated that inhibition of histone deacetylation by TSA in neuronal cells affect the expressions of c-fos and c-jun genes, suggesting histone acetylation might play a role in the regulation of both genes expressions after kainate stimulation.