TISSUE-PLASMINOGEN ACTIVATOR IS INDUCED AS AN IMMEDIATE EARLY GENE DURING SEIZURE, KINDLING AND LONG-TERM POTENTIATION
TISSUE-PLASMINOGEN ACTIVATOR IS INDUCED AS AN IMMEDIATE EARLY GENE DURING SEIZURE, KINDLING AND LONG-TERM POTENTIATION
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DOI：
10.1038/361453a0
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发表时间：
1993-02-04
期刊：
影响因子：
64.8
通讯作者：
KUHL, D
中科院分区：
文献类型：
--
作者：
QIAN, Z;GILBERT, ME;KUHL, D
长期记忆需要蛋白质和信使RNA的合成1，2表明学习诱导的神经活动启动了基因表达的级联反应3。在这里，我们使用差异筛选，以确定五个立即早期基因诱导的神经元活动。其中之一是组织纤溶酶原激活物（tPA），一种细胞外丝氨酸蛋白酶，其通过三种活动依赖性事件以不同的空间模式在脑中诱导：（1）惊厥发作增加tPA在整个脑中的表达;（2）贯穿通路的刺激产生癫痫样后放电，其最终导致点燃增加整个海马体双侧的tPA水平;（3）短暂高频刺激穿通通路产生长时程增强（LTP），引起NMDA（N-甲基-D-天冬氨酸）受体介导的tPA mRNA水平的增加，其仅限于同侧齿状回的颗粒细胞。由于tPA的释放与形态分化相关4 -6，tPA表达的增加可能在伴随活性依赖性可塑性的结构变化中起作用7 -10。
THE requirement of protein and messenger RNA synthesis for long-term memory1,2 suggests that neural activity induced by learning initiates a cascade of gene expression3. Here we use differential screening to identify five immediate-early genes induced by neuronal activity. One of these is tissue-plasminogen activator (tPA), an extracellular serine protease, which is induced with different spatial patterns in the brain by three activity-dependent events: (1) convulsive seizure increases expression of tPA in the whole brain; (2) stimulation of the perforant path produces an epileptiform after-discharge that ultimately leads to kindling increases the levels of tPA throughout the hippocampus bilaterally; and (3) brief high-frequency stimulation of the perforant path that produces long-term potentiation (LTP) causes an NMDA (N-methyl-D-aspartate) receptor-mediated increase in the levels of tPA mRNA which is restricted to the granule cells of the ipsilateral dentate gyrus. As release of tPA is correlated with morphological differentiation4-6, the increased expression of tPA may play a role in the structural changes that accompany activity-dependent plasticity7-10.