Dorsal Hippocampus ERK2 Signaling Mediates Anxiolytic-Related Behavior in Male Rats
Dorsal Hippocampus ERK2 Signaling Mediates Anxiolytic-Related Behavior in Male Rats
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DOI：
10.1177/2470547019897030
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发表时间：
2019-01
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影响因子：
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通讯作者：
Jorge A Sierra-Fonseca;Lyonna F. Parise;F. Flores-Ramirez;E. Robles;Israel Garcia-Carachure;S. Iñiguez
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文献类型：
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作者：
Jorge A Sierra-Fonseca;Lyonna F. Parise;F. Flores-Ramirez;E. Robles;Israel Garcia-Carachure;S. Iñiguez
背景焦虑症是世界范围内最常见的神经病理学，但这些疾病背后的确切神经机制仍不清楚。海马体在介导焦虑相关反应中起作用，这可以使用行为测定（例如高架十字迷宫）在啮齿动物中建模。然而，高架十字迷宫中情感相关行为背后的分子标记还没有得到很好的理解。方法我们使用单纯疱疹病毒载体递送在成年Sprague-Dawley雄性大鼠的背海马内过表达细胞外信号调节激酶-2，这是一种已知与抑郁和焦虑有关的信号分子。病毒递送后三天，我们评估了高架十字迷宫上的焦虑样反应或旷场测试上的一般运动活动。结果与对照组相比，背侧海马细胞外信号调节激酶-2过表达的大鼠在高架十字迷宫中表现出抗焦虑样表型，在开放臂的时间增加，在封闭臂的时间减少。此外，在实验组之间的旷场试验中未观察到作为病毒输注函数的运动活性的变化。结论病毒介导的海马细胞外信号调节激酶2信号通路的增加在降低大鼠高架十字迷宫的焦虑反应中起重要作用。因此，我们的数据提供了结构效度，至少部分，介导的抗焦虑样行为的啮齿动物模型的焦虑研究的分子机制。
Background Anxiety disorders are the most common neuropathologies worldwide, but the precise neuronal mechanisms that underlie these disorders remain unknown. The hippocampus plays a role in mediating anxiety-related responses, which can be modeled in rodents using behavioral assays, such as the elevated plus maze. Yet, the molecular markers that underlie affect-related behavior on the elevated plus maze are not well understood. Methods We used herpes simplex virus vector delivery to overexpress extracellular signal-regulated kinase-2, a signaling molecule known to be involved in depression and anxiety, within the dorsal hippocampus of adult Sprague-Dawley male rats. Three days post virus delivery, we assessed anxiety-like responses on the elevated plus maze or general locomotor activity on the open field test. Results When compared to controls, rats overexpressing extracellular signal-regulated kinase-2 in the dorsal hippocampus displayed an anxiolytic-like phenotype, per increases in time spent in the open arms, and less time in the closed arms, of the elevated plus maze. Furthermore, no changes in locomotor activity as a function of virus infusion were observed on the open field test between the experimental groups. Conclusion This investigation demonstrates that virus-mediated increases of extracellular signal-regulated kinase-2 signaling, within the hippocampus, plays a critical role in decreasing anxiogenic responses on the rat elevated plus maze. As such, our data provide construct validity, at least in part, to the molecular mechanisms that mediate anxiolytic-like behavior in rodent models for the study of anxiety.