Department of Pharmacological Sciences, Stony Brook University, Stony Brook, NY 11733, USA.
Brain Res. 2010 Apr 22;1326:135-42. doi: 10.1016/j.brainres.2009.12.095. Epub 2010 Feb 12.
Tissue Plasminogen Activator (tPA) is a serine protease expressed in different areas of the mammalian brain. It has been used clinically to dissolve clots and shown to have a role in neurodegeneration. Early studies suggested that tPA plays an important role in the processes of learning and memory, demonstrated at the level of behavior and synaptic plasticity. Herein, we extend the behavioral characterization of these mice to the related dimension of exploratory-related behavior using an extensive battery of behavioral tests as well as the neurotransmitter metabolism associated with the behavioral measures. Our results indicate a behavior tendency in these mice consistent with "impulsivity" or reduced exploratory inhibition. These patterns are accompanied by decreased levels of serotonin in several brain regions important in behavioral regulation in the tPA(-/-) mice compared to control animals. Systemic administration of fluoxetine reversed the behavioral disinhibition of tPA(-/-) mice, further supporting an important alteration in behavior regulation mediated by serotonin systems as underappreciated but important element of the behavioral phenotype of these animals.
组织型纤溶酶原激活物（tPA）是一种在哺乳动物大脑不同区域表达的丝氨酸蛋白酶。它已在临床上用于溶解血栓，并被证明在神经退行性变中起作用。早期研究表明，tPA 在学习和记忆的过程中发挥着重要作用，这在行为和突触可塑性水平上得到了证明。在此，我们使用一系列广泛的行为测试以及与行为测量相关的神经递质代谢，将这些小鼠的行为特征扩展到相关的探索性行为维度。我们的结果表明，这些小鼠的行为趋势与“冲动”或探索抑制减少一致。与对照动物相比，tPA(-/-) 小鼠几种对行为调节很重要的脑区中的 5-羟色胺水平降低，这些模式伴随着降低。系统给予氟西汀可逆转 tPA(-/-) 小鼠的行为去抑制作用，进一步支持 5-羟色胺系统介导的行为调节的重要改变，这是这些动物行为表型中被低估但重要的因素。
