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Urokinase receptor and tissue plasminogen activator as immediate‐early genes in pentylenetetrazole‐induced seizures in the mouse brain
Author(s) -
Shmakova Anna A.,
Rubina Kseniya A.,
Rysenkova Karina D.,
Gruzdeva Anna M.,
Ivashkina Olga I.,
Anokhin Konstantin V.,
Tkachuk Vsevolod A.,
Semina Ekaterina V.
Publication year - 2020
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/ejn.14584
Subject(s) - urokinase receptor , tissue plasminogen activator , epileptogenesis , urokinase , immediate early gene , plasminogen activator , central nervous system , gene expression , biology , activator (genetics) , receptor , endocrinology , chemistry , medicine , microbiology and biotechnology , neuroscience , hippocampus , gene , biochemistry
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 expression of tissue plasminogen activator (tPA) and urokinase receptor (uPAR) mRNA was strongly increased in the mouse cerebral cortex, hippocampus, striatum and amygdala as early as 3 hr 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 gene induction and uPAR gene induction were 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 hr following seizures, urokinase and plasminogen activator inhibitor‐1 gene expression showed a delayed activation only at 3 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.