title: ERK2 contributes to the control of social behaviors in mice.
abstract: 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 nest-building, 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 Erk2 CKO mice 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 that ERK2 has complex and multiple roles in the CNS, with important implications for human psychiatric disorders characterized by deficits in social behaviors.
authors.affiliation: Department of Anesthesiology, National Defense Medical College, 359-8513 Tokorozawa, Japan. ys@ndmc.ac.jp
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Satoh
authors.forename: Shogo
authors.initials: S
authors.lastname: Endo
authors.forename: Takahiro
authors.initials: T
authors.lastname: Nakata
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Kobayashi
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Yamada
authors.forename: Toshio
authors.initials: T
authors.lastname: Ikeda
authors.forename: Atsuya
authors.initials: A
authors.lastname: Takeuchi
authors.forename: Takeshi
authors.initials: T
authors.lastname: Hiramoto
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Watanabe
authors.forename: Tomiei
authors.initials: T
authors.lastname: Kazama
mesh_terms: D000818:Animals; D015536:Down-Regulation / Q000235:genetics; D005260:Female; D008297:Male; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D019950:Mitogen-Activated Protein Kinase 1 / Q000235:genetics / Q000502:physiology*; D009043:Motor Activity / Q000235:genetics / Q000502:physiology*; D011247:Pregnancy; D012919:Social Behavior
chemical_list: C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1