Akt2 Deficiency is Associated with Anxiety and Depressive Behavior in Mice
Akt2 Deficiency is Associated with Anxiety and Depressive Behavior in Mice
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DOI：
10.1159/000354478
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发表时间：
2013-01-01
影响因子：
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通讯作者：
Lang, Undine E.
中科院分区：
文献类型：
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作者：
Leibrock, Christina;Ackermann, Teresa F.;Lang, Undine E.
背景：与严重抑郁障碍和焦虑障碍相关的经济负担使这两种疾病成为最常见和最令人衰弱的精神疾病。到目前为止，这些高度相关疾病的病理生理、成功治疗和预防的确切细胞和分子机制尚未确定。Akt2是磷脂酰肌醇-3(PI3K)/糖原合成酶3激酶(GSK3)信号通路中的关键蛋白，进而参与脑源性神经营养因子(BDNF)对恐惧记忆、情绪稳定和几种抗抑郁药物的作用。因此，本研究探讨了Akt2对小鼠行为的影响。方法：用Akt2基因敲除小鼠(AKT(-/-))和相应的野生型小鼠(AKT(+/+))进行行为学研究(旷场、光暗箱、O迷宫、强迫游泳实验、涌现实验、物体探索实验、Morris水迷宫、径向迷宫)。结果：AKT(-/-)小鼠的焦虑和抑郁行为明显高于AKT(+/+)小鼠。AKT(-/-)小鼠在认知方面没有受损，但在几项行为测试(O-迷宫测试、光暗盒测试、开场测试)中表现出更多的焦虑。此外，AKT(-/-)小鼠在强迫游泳测试中漂浮的时间更长，这是实验性抑郁症的典型特征。结论：Akt2可能是抑郁和焦虑的病理生理学过程中的一个关键因素。版权所有(C)2013 S.Karger AG，巴塞尔
Background: The economic burden associated with major depressive disorder and anxiety disorders render both disorders the most common and debilitating psychiatric illnesses. To date, the exact cellular and molecular mechanisms underlying the pathophysiology, successful treatment and prevention of these highly associated disorders have not been identified. Akt2 is a key protein in the phosphatidylinositide-3 (PI3K)/glycogen synthase 3 kinase (GSK3) signaling pathway, which in turn is involved in brain-derived neurotrophic factor (BDNF) effects on fear memory, mood stabilisation and action of several antidepressant drugs. The present study thus explored the impact of Akt2 on behaviour of mice. Methods: Behavioural studies (Open-Field, Light-Dark box, O-Maze, Forced Swimming Test, Emergence Test, Object Exploration Test, Morris Water Maze, Radial Maze) have been performed with Akt2 knockout mice (akt(-/-)) and corresponding wild type mice (akt(+/+)). Results: Anxiety and depressive behavior was significantly higher in akt(-/-)than in akt(+/+) mice. The akt(-/-)mice were cognitively unimpaired but displayed increased anxiety in several behavioral tests (O-Maze test, Light-Dark box, Open Field test). Moreover, akt(-/-)mice spent more time floating in the Forced Swimming test, which is a classical feature of experimental depression. Conclusion: Akt2 might be a key factor in the pathophysiology of depression and anxiety.Copyright (C) 2013 S. Karger AG, Basel