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

来自 EBSCO

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阅读量：

117

作者：

SE Tsirka，A Gualandris，DG Amaral，S Strickland

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摘要：

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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关键词：

Excitatory Amino Acid Agonists Kainic Acid Nerve Degeneration Tissue Plasminogen Activator metabolism 兴奋性氨基酸激动剂红藻氨酸神经变性

DOI：

10.1038/377340a0

被引量：

1436

年份：

1995