Transgenic up-regulation of alpha-CaMKII in forebrain leads to increased anxiety-like behaviors and aggression

Shunsuke Hasegawa, Takahiro Furuichi, Taro Yoshida, Kengo Endoh, Kenichi Kato, Megumi Sado, Ryouta Maeda, Aya Kitamoto, Takahisa Miyao, Ryosuke Suzuki, Seiichi Homma, Shoichi Masushige, Yasushi Kajii, Satoshi Kida

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51 Citations (Scopus)

Abstract

Background. 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. Results. 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. Conclusion. 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.

Original languageEnglish
Article number6
JournalMolecular brain
Volume2
Issue number1
DOIs
Publication statusPublished - 2009 May 7

ASJC Scopus subject areas

  • Molecular Biology
  • Cellular and Molecular Neuroscience

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    Hasegawa, S., Furuichi, T., Yoshida, T., Endoh, K., Kato, K., Sado, M., Maeda, R., Kitamoto, A., Miyao, T., Suzuki, R., Homma, S., Masushige, S., Kajii, Y., & Kida, S. (2009). Transgenic up-regulation of alpha-CaMKII in forebrain leads to increased anxiety-like behaviors and aggression. Molecular brain, 2(1), [6]. https://doi.org/10.1186/1756-6606-2-6