Urokinase receptor and tissue plasminogen activator as immediate early genes in pentylenetetrazole‐induced seizures in the mouse brain

Urokinase receptor and tissue plasminogen activator as immediate early genes in pentylenetetrazole‐induced seizures in the mouse brain:

Abstract

Epileptogenesis progressively leads to the rearrangement of normal neuronal networks into more excitable ones and can be viewed as a form of neuroplasticity the molecular mechanisms of which still remain obscure. Here we studied pentylenetetrazole seizure‐induced regulation of genes for plasminogen activator system in the mouse brain. We found that tissue plasminogen activator (tPA) and urokinase receptor (uPAR) mRNA expression was strongly increased in the mouse cerebral cortex, hippocampus, striatum and amygdala as early as three hours after pentylenetetrazole seizures. Such early activity‐induced expression of uPAR in the central nervous system has not been demonstrated before. uPAR mRNA accumulation was followed by elevation of uPAR protein, indicating a complete transcription‐translation process. Both tPA and uPAR gene induction was independent of the protein synthesis, suggesting that they are regulated by neural activity as immediate early genes. In contrast to tPA and uPAR genes, the expression of which returned to the basal level 6 hours following seizures, urokinase and plasminogen activator inhibitor‐1 gene expression showed a delayed activation only at three days after seizures. In conclusion, our results suggest an important sensitivity of the brain plasminogen activator system to seizure activity which raises the question of its role in activity‐dependent neural tissue remodeling in pathological and normal conditions.