Department of Bioscience, Faculty of Applied Bioscience, Tokyo University of Agriculture, Tokyo 156-8502, Japan.
Mol Brain. 2009 Mar 4;2:6. doi: 10.1186/1756-6606-2-6.
Previous studies have demonstrated essential roles for alpha-calcium/calmodulin-dependent protein kinase II (alpha-CaMKII) in learning, memory and long-term potentiation (LTP). However, previous studies have also shown that alpha-CaMKII (+/-) heterozygous knockout mice display a dramatic decrease in anxiety-like and fearful behaviors, and an increase in defensive aggression. These findings indicated that alpha-CaMKII is important not only for learning and memory but also for emotional behaviors. In this study, to understand the roles of alpha-CaMKII in emotional behavior, we generated transgenic mice overexpressing alpha-CaMKII in the forebrain and analyzed their behavioral phenotypes.
We generated transgenic mice overexpressing alpha-CaMKII in the forebrain under the control of the alpha-CaMKII promoter. In contrast to alpha-CaMKII (+/-) heterozygous knockout mice, alpha-CaMKII overexpressing mice display an increase in anxiety-like behaviors in open field, elevated zero maze, light-dark transition and social interaction tests, and a decrease in locomotor activity in their home cages and novel environments; these phenotypes were the opposite to those observed in alpha-CaMKII (+/-) heterozygous knockout mice. In addition, similarly with alpha-CaMKII (+/-) heterozygous knockout mice, alpha-CaMKII overexpressing mice display an increase in aggression. However, in contrast to the increase in defensive aggression observed in alpha-CaMKII (+/-) heterozygous knockout mice, alpha-CaMKII overexpressing mice display an increase in offensive aggression.
Up-regulation of alpha-CaMKII expression in the forebrain leads to an increase in anxiety-like behaviors and offensive aggression. From the comparisons with previous findings, we suggest that the expression levels of alpha-CaMKII are associated with the state of emotion; the expression level of alpha-CaMKII positively correlates with the anxiety state and strongly affects aggressive behavior.
先前的研究表明，α-钙/钙调蛋白依赖性蛋白激酶 II（α-CaMKII）在学习、记忆和长时程增强（LTP）中起着重要作用。然而，先前的研究也表明，α-CaMKII（+/-）杂合敲除小鼠表现出明显的焦虑样和恐惧行为减少，以及防御性攻击增加。这些发现表明，α-CaMKII 不仅对学习和记忆很重要，而且对情绪行为也很重要。在这项研究中，为了了解 α-CaMKII 在情绪行为中的作用，我们生成了在大脑前脑过度表达 α-CaMKII 的转基因小鼠，并分析了它们的行为表型。
我们生成了在大脑前脑过度表达 α-CaMKII 的转基因小鼠，该表达受 α-CaMKII 启动子的控制。与 α-CaMKII（+/-）杂合敲除小鼠相比，α-CaMKII 过表达小鼠在旷场、高架十字迷宫、明暗过渡和社交互动测试中表现出焦虑样行为增加，在其笼内和新环境中的运动活性降低；这些表型与在 α-CaMKII（+/-）杂合敲除小鼠中观察到的相反。此外，与 α-CaMKII（+/-）杂合敲除小鼠类似，α-CaMKII 过表达小鼠表现出攻击性增加。然而，与在 α-CaMKII（+/-）杂合敲除小鼠中观察到的防御性攻击增加相反，α-CaMKII 过表达小鼠表现出攻击性攻击增加。
大脑前脑 α-CaMKII 表达的上调导致焦虑样行为和攻击性攻击的增加。与先前的发现相比，我们认为 α-CaMKII 的表达水平与情绪状态有关；α-CaMKII 的表达水平与焦虑状态呈正相关，并强烈影响攻击行为。
