Neuronal excitation-driven and AP-1-dependent activation of tissue inhibitor of metalloproteinases-1 gene expression in rodent hippocampus

Understanding of biological function of AP-1 transcription factor in centra l nervous system may greatly benefit from identifying its target genes. In this study, we present several lines of evidence implying A9-1 in regulatin g expression of tissue inhibitor of metalloproteinases-l (timp-1) gene in r odent hippocampus in response to increased neuronal excitation. Such a noti on is supported by the findings that timp-1 mRNA accumulation occurs in the rat hippocampus after either kainate- or pentylenetetrazole-evoked seizure s with a delayed, in comparison with AP-1 components, time course, as well as with spatial overlap with c-Fos protein (major inducible AP-1 component) expression. Furthermore, AP-1 sequence derived from timp-1 promoter is spe cifically bound by hippocampal AP-1 proteins after treating the rats with e ither pro-convulsive agent. Finally, timp-1 promoter responds to excitatory activation both in vivo, in transgenic mice harboring the timp-LacZ gene c onstruct, and in vitro in neurons of the hippocampal dentate gyrus cultures , These findings suggest that the AP-1 transcription factor may exert its r ole in the brain through affecting extracellular matrix remodeling.