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TISSUE-PLASMINOGEN ACTIVATOR IS INDUCED AS AN IMMEDIATE-EARLY GENE DURING SEIZURE, KINDLING, AND LONG-TERM POTENTIATION
Citation:
Qian, Z., M. Colicso, E. Kandel, D. Kuhl, AND M. Gilbert. TISSUE-PLASMINOGEN ACTIVATOR IS INDUCED AS AN IMMEDIATE-EARLY GENE DURING SEIZURE, KINDLING, AND LONG-TERM POTENTIATION. U.S. Environmental Protection Agency, Washington, D.C., EPA/600/J-94/081 (NTIS PB94141496).
Description:
Activity-dependent genes in brain have been identified using differential screening of hippocampal cDNA library from rats exposed to metrazol seizures under conditions of superconduction. Five immediate early genes whose expression is elevated by neural activity were identified. hree of these genes have not been described before. ourth gene encodes a previously described nerve-growth factor-inducible protein of unknown function. e focus here on the fifth gene, which we have identified as a tissue-plasminogen activator (tPA), an extracellular serine protease. tPA MRNA is induced in different ways by three activity-dependent events: metrazol triggered convulsions increase expression throughout the brain kindling stimulation to the perforant path to induce an afterdischarge leads to an increase bilaterally hroughout the hippocampus; longterm potentiation (LTP) increases PA mRNA in the granule cells of the dentate gyrus ipsilateral to the stimulated site. his restricted expression induced by LTP was blocked by the NMDA antagonist, MK-801, suggesting that tPA expression and LTP involve similar inductive mechanisms. timuli that evoke kindling and LTP induce morphological changes in hippocampal neurons. ince tPA is released from the growth cone, its increased expression may play a role in structural changes that accompany activity-dependent plasticity.