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Publication : Excitotoxin-induced neuronal degeneration and seizure are mediated by tissue plasminogen activator.

First Author  Tsirka SE Year  1995
Journal  Nature Volume  377
Issue  6547 Pages  340-4
PubMed ID  7566088 Mgi Jnum  J:28943
Mgi Id  MGI:76480 Doi  10.1038/377340a0
Citation  Tsirka SE, et al. (1995) Excitotoxin-induced neuronal degeneration and seizure are mediated by tissue plasminogen activator. Nature 377(6547):340-4
abstractText  Neuronal degeneration in the hippocampus, a region of the brain important for acquisition of memory in humans, occurs in various pathological conditions, including Alzheimer's disease, brain ischaemia and epilepsy. When neuronal activity is stimulated in the adult rat and mouse hippocampus, tissue plasminogen activator (tPA), a serine protease that converts inactive plasminogen to the active protease plasmin, is transcriptionally induced. The activity of tPA in neural tissue is correlated with neurite outgrowth, regeneration and migration, suggesting that it might be involved in neuronal plasticity. Here we show that tPA is produced primarily by microglia in the hippocampus. Using excitotoxins to induce neuronal cell loss, we demonstrate that tPA-deficient mice are resistant to neuronal degeneration. These mice are also less susceptible to pharmacologically induced seizures than wild-type mice. These findings identify a role for tPA in neuronal degeneration and seizure.
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