Decreased serotonin levels associated with behavioral disinhibition in tissue plasminogen activator deficient (tPA-/-) mice.
Decreased serotonin levels associated with behavioral disinhibition in tissue plasminogen activator deficient (tPA-/-) mice.
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DOI：
10.1016/j.brainres.2009.12.095
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发表时间：
2010-04-22
期刊：
影响因子：
2.9
通讯作者：
Tsirka, Stella E.
中科院分区：
文献类型：
--
作者：
Pothakos, Konstantinos;Robinson, John K.;Gravanis, Iordanis;Marsteller, Douglas A.;Dewey, Stephen L.;Tsirka, Stella E.
组织纤溶酶原激活物（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凝块，并显示出在神经变性中起作用。早期的研究表明，tPA在学习和记忆过程中起着重要作用，表现在行为和突触可塑性的水平上。在此，我们将这些小鼠的行为特征扩展到探索相关行为的相关维度，使用广泛的行为测试以及与行为测量相关的神经递质代谢。我们的研究结果表明，这些小鼠的行为倾向与“冲动”或减少探索性抑制一致。与对照动物相比，这些模式伴随着在tPA - / -小鼠中对行为调节重要的几个脑区血清素水平的降低。全身给药氟西汀逆转了tPA - / -小鼠的行为去抑制，进一步支持了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的重要因素，但未被重视。
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.
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