Tissue plasminogen activator in the amygdala is critical for stress-induced anxiety-like behavior
Tissue plasminogen activator in the amygdala is critical for stress-induced anxiety-like behavior
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DOI：
10.1038/nn998
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发表时间：
2003-02-01
影响因子：
25
通讯作者：
Strickland, S
中科院分区：
文献类型：
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作者：
Pawlak, R;Magarinos, AM;Strickland, S
尽管神经应激回路已经被发现，但关于应激诱导的神经元可塑性导致恐惧和焦虑的机制却知之甚少。在这里，我们发现在急性束缚应激下，中央和内侧杏仁核中的丝氨酸蛋白酶组织纤溶酶原激活物(TPA)表达上调，在那里它促进了应激相关的神经元重塑，并随后被纤溶酶原激活物抑制物-1(PAI-1)抑制。这些事件发生在压力诱导的小鼠焦虑样行为增加之前。TPA基因被破坏的小鼠在每天禁欲长达三周后没有表现出焦虑，表现出减弱的神经元重塑以及不适应的激素反应。这些研究支持这样一种观点，即tPA对压力后焦虑样行为的发展至关重要。
Although neuronal stress circuits have been identified, little is known about the mechanisms that underlie the stress-induced neuronal plasticity leading to fear and anxiety. Here we found that the serine protease tissue-plasminogen activator (tPA) was upregulated in the central and medial amygdala by acute restraint stress, where it promoted stress-related neuronal remodeling and was subsequently inhibited by plasminogen activator inhibitor-1 (PAI-1). These events preceded stress-induced increases in anxiety-like behavior of mice. Mice in which the tPA gene has been disrupted did not show anxiety after up to three weeks of daily restraint and showed attenuated neuronal remodeling as well as a maladaptive hormonal response. These studies support the idea that tPA is critical for the development of anxiety-like behavior after stress.