Rapid, specific and active site-catalyzed effect of tissue-plasminogen activator on hippocampus-dependent learning in mice
Rapid, specific and active site-catalyzed effect of tissue-plasminogen activator on hippocampus-dependent learning in mice
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DOI：
10.1016/s0306-4522(02)00166-5
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发表时间：
2002-01-01
期刊：
影响因子：
3.3
通讯作者：
Takada, A
中科院分区：
文献类型：
--
作者：
Pawlak, R;Nagai, N;Takada, A
在本研究中，我们训练了组织纤溶酶原激活剂（tPA）敲除（tPA -/-）和野生型（tPA +/+）雄性小鼠进行降压抑制性回避学习，这是一种海马依赖性任务。 tPA -/- 在训练后 90 分钟、1 天、2 天和 7 天时表现出显着缩短的潜伏期，表明这些动物存在学习缺陷（与 tPA +/+ 相比，P < 0.05）。两种小鼠品系的运动活动、高架十字迷宫中的焦虑水平以及疼痛阈值没有差异。 tPA -/- 的学习障碍通过更密集的训练得以克服。学习缺陷也可以通过有限的海马内 tPA 输送（训练前输注 2 小时；与对照相比，P < 0.05）得到部分恢复，但不能通过尿激酶纤溶酶原激活剂的输送得到部分恢复，这表明学习中对 tPA 的迫切需要。 tPA 的有益作用被其抑制剂 tPA-STOP 的共同输注所消除，这表明 tPA 对学习的促进作用需要一个蛋白水解步骤。然而，海马中的 tPA 活性对于输注 tPA 的 tPA -/- 小鼠的有效记忆检索并不是必不可少的。因此，tPA 的快速、特异性和蛋白水解作用有利于海马依赖性学习，但不能检索先前获得的信息。 (C) 2002 国际广播组织。由爱思唯尔科学有限公司出版。保留所有权利。
In the present study we trained tissue-plasminogen activator (tPA)-knockout (tPA -/-) and wild-type (tPA +/+) male mice in step-down inhibitory avoidance learning, a hippocampus-dependent task. tPA -/- displayed significantly shorter latencies to step down at 90 min, one, two and seven days after training indicating the learning deficit in these animals (P < 0.05 vs tPA +/+). The locomotor activity, the level of anxiety in an elevated-plus maze, as well as the pain threshold did not differ between the two strains of mice. The learning disability of tPA -/- was overcome by more intense training. The learning deficit was also partially restored by limited intrahippocarnpal delivery of tPA (infused for 2 h before training; P < 0.05 vs control), but not by the delivery of urokinase plasminogen activator, indicating the acute need for tPA in learning. The beneficial effect of tPA was abolished by co-infusion of its inhibitor tPA-STOP, indicating that the facilitatory effect of tPA on learning requires a proteolytic step. However, tPA activity in the hippocampus was not indispensable for effective memory retrieval in tPA-infused tPA -/- mice. Thus, rapid, specific and proteolytic action of tPA facilitates hippocampus-dependent learning, but not retrieval of previously acquired information. (C) 2002 IBRO. Published by Elsevier Science Ltd. All rights reserved.