Environmental stimulation changes tissue-type plasminogen activator activity in the adult mouse hippocampus

Tissue-type plasminogen activator (tPA) plays an important role in synaptic plasticity and contributes to several brain functions such as memory, learning, and behaviours. Although a number of studies have demonstrated that various kinds of stimuli such as electrophysiological stimulation, excitotoxic injury, and stress change tPA activity in the brain, no studies have ever examined whether environmental stimulation affect tPA activity in the brain. The aim of this study is to clarify the effect of environmental enrichment on tPA activity in the hippocampus and cerebral cortex of adult mouse brain. Zymographic analysis revealed that hippocampal tPA activity was higher in enriched mice than in standard-caged mice, whereas no significant changes in the cerebral cortex were detected between enriched and control mice. Enrichment-enhanced tPA activity reverted to the pre-enrichment level after mice were returned to a standard housing condition, suggesting that tPA upregulation is stimulation-dependent and reversible. These results suggest that tPA activity is regulated reversibly in an experience-dependent manner in the adult hippocampus.