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


CONCLUSIONS
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.
Hasegawa
Shunsuke
S
Department of Bioscience, Faculty of Applied Bioscience, Tokyo University of Agriculture, Tokyo 156-8502, Japan. 56060003@nodai.ac.jp
Furuichi
Takahiro
T
Yoshida
Taro
T
Endoh
Kengo
K
Kato
Kenichi
K
Sado
Megumi
M
Maeda
Ryouta
R
Kitamoto
Aya
A
Miyao
Takahisa
T
Suzuki
Ryosuke
R
Homma
Seiichi
S
Masushige
Shoichi
S
Kajii
Yasushi
Y
Kida
Satoshi
S
D000374:Aggression; D000818:Animals; D001007:Anxiety / Q000201:enzymology*; D001522:Behavior, Animal; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000235:genetics* / Q000378:metabolism; D005239:Fear; D015971:Gene Expression Regulation, Enzymologic; D006624:Hippocampus / Q000201:enzymology / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D009043:Motor Activity; D016548:Prosencephalon / Q000201:enzymology* / Q000473:pathology; D045442:Rotarod Performance Test; D015854:Up-Regulation / Q000235:genetics*
D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2