TY - JOUR
T1 - ERK2 contributes to the control of social behaviors in mice
AU - Satoh, Yasushi
AU - Endo, Shogo
AU - Nakata, Takahiro
AU - Kobayashi, Yasushi
AU - Yamada, Kazuyuki
AU - Ikeda, Toshio
AU - Takeuchi, Atsuya
AU - Hiramoto, Takeshi
AU - Watanabe, Yasuhiro
AU - Kazama, Tomiei
PY - 2011/8/17
Y1 - 2011/8/17
N2 - Signaling through extracellular signal-regulated kinase (ERK) is important in multiple signal transduction networks in the CNS. However, the specific role of ERK2 in in vivo brain functions is not fully understood. Here we show that ERK2 play a critical role in regulating social behaviors as well as cognitive and emotional behaviors in mice. To study the brain function of ERK2, we used a conditional, region-specific, genetic approach to target Erk2 using the Cre/loxP strategy with a nestin promoter-driven cre transgenic mouse line to induce recombination in the CNS. The resulting Erk2 conditional knock-out (CKO) mice, in which Erk2 was abrogated specifically in the CNS, were viable and fertile with a normal appearance. These mice, however, exhibited marked anomalies in multiple aspects of social behaviors related to facets of autism-spectrum disorders: elevated aggressive behaviors, deficits in maternal nurturing, poor nestbuilding, and lower levels of social familiarity and social interaction. Erk2 CKO mice also exhibited decreased anxiety-related behaviors and impaired long-term memory. Pharmacological inhibition of ERK1 phosphorylation in Erk2CKOmice did not affect the impairments in social behaviors and learning disabilities, indicating that ERK2, but not ERK1 plays a critical role in these behaviors. Our findings suggest thatERK2has complex and multiple roles in the CNS, with important implications forhumanpsychiatric disorders characterized by deficits in social behaviors.
AB - Signaling through extracellular signal-regulated kinase (ERK) is important in multiple signal transduction networks in the CNS. However, the specific role of ERK2 in in vivo brain functions is not fully understood. Here we show that ERK2 play a critical role in regulating social behaviors as well as cognitive and emotional behaviors in mice. To study the brain function of ERK2, we used a conditional, region-specific, genetic approach to target Erk2 using the Cre/loxP strategy with a nestin promoter-driven cre transgenic mouse line to induce recombination in the CNS. The resulting Erk2 conditional knock-out (CKO) mice, in which Erk2 was abrogated specifically in the CNS, were viable and fertile with a normal appearance. These mice, however, exhibited marked anomalies in multiple aspects of social behaviors related to facets of autism-spectrum disorders: elevated aggressive behaviors, deficits in maternal nurturing, poor nestbuilding, and lower levels of social familiarity and social interaction. Erk2 CKO mice also exhibited decreased anxiety-related behaviors and impaired long-term memory. Pharmacological inhibition of ERK1 phosphorylation in Erk2CKOmice did not affect the impairments in social behaviors and learning disabilities, indicating that ERK2, but not ERK1 plays a critical role in these behaviors. Our findings suggest thatERK2has complex and multiple roles in the CNS, with important implications forhumanpsychiatric disorders characterized by deficits in social behaviors.
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U2 - 10.1523/JNEUROSCI.2349-11.2011
DO - 10.1523/JNEUROSCI.2349-11.2011
M3 - Article
C2 - 21849556
AN - SCOPUS:80051732557
SN - 0270-6474
VL - 31
SP - 11953
EP - 11967
JO - Journal of Neuroscience
JF - Journal of Neuroscience
IS - 33
ER -