Altered behavior in mice with deletion of the alpha2-antiplasmin gene.
Altered behavior in mice with deletion of the alpha2-antiplasmin gene.
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DOI：
10.1371/journal.pone.0097947
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Matsuno H
中科院分区：
文献类型：
--
作者：
Kawashita E;Kanno Y;Ikeda K;Kuretake H;Matsuo O;Matsuno H
α2-抗纤溶酶（α 2-antiplasmin，α2AP）蛋白是纤溶酶的主要生理抑制剂，在海马、皮质、下丘脑和小脑等脑组织均有表达，提示α2AP在脑功能中具有潜在的作用。然而，α2AP参与脑功能目前尚不清楚。本研究的目的是研究α2AP基因缺失对小鼠行为的影响。采用悬丝试验和转棒试验检测运动功能。采用重复旋转杆实验、Y迷宫实验、Morris水迷宫实验、被动回避实验、穿梭回避实验和条件性恐惧实验评价大鼠的认知功能。采用旷场试验、明暗转换试验或悬尾试验确定α2AP与焦虑或抑郁样行为的关系。与α2AP+/+小鼠相比，α2AP敲除（α2AP−/−）小鼠表现出运动功能受损。α2AP−/−小鼠在运动学习、工作记忆、空间记忆和恐惧条件记忆方面也表现出损伤。此外，α2AP的缺失诱导焦虑样行为，并引起抗抑郁样效应的尾部悬挂。因此，我们的研究结果表明α2AP是运动功能、认知功能、焦虑样行为和抑郁样行为的重要介质，为α2AP在脑功能中的作用提供了新的见解。
The α2-antiplasmin (α2AP) protein is known to be a principal physiological inhibitor of plasmin, and is expressed in various part of the brain, including the hippocampus, cortex, hypothalamus and cerebellum, thus suggesting a potential role for α2AP in brain functions. However, the involvement of α2AP in brain functions is currently unclear. The goal of this study was to investigate the effects of the deletion of the α2AP gene on the behavior of mice. The motor function was examined by the wire hang test and rotarod test. To evaluate the cognitive function, a repeated rotarod test, Y-maze test, Morris water maze test, passive or shuttle avoidance test and fear conditioning test were performed. An open field test, dark/light transition test or tail suspension test was performed to determine the involvement of α2AP in anxiety or depression-like behavior. The α2AP knockout (α2AP−/−) mice exhibited impaired motor function compared with α2AP+/+ mice. The α2AP−/− mice also exhibited impairments in motor learning, working memory, spatial memory and fear conditioning memory. Furthermore, the deletion of α2AP induced anxiety-like behavior, and caused an anti-depression-like effect in tail suspension. Therefore, our findings suggest that α2AP is a crucial mediator of motor function, cognitive function, anxiety-like behavior and depression-like behavior, providing new insights into the role of α2AP in the brain functions.
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