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Study for the Function of ERK2 in the Brain Using ERK2 Conditional Knockout Mouse

Research Project

Project/Area Number 22500304
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Neuroscience in general
Research Institution防衛医科大学校 (2012)
National Defense Medical College (2010-2011)

Principal Investigator

SATOH Yasushi  防衛医科大学校, 病院, 講師 (10505267)

Co-Investigator(Kenkyū-buntansha) ENDO Shogo  地方独立行政法人東京都健康長寿医療センター研究所, 老化制御研究チーム, 研究部長 (60192514)
ADACHI Takeshi  防衛医科大学校, 医学教育学部医学科専門課程, 教授 (50231931)
Project Period (FY) 2010 – 2012
Project Status Completed (Fiscal Year 2012)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2012: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2011: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2010: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
KeywordsERK / 神経 / 細胞内情報伝達 / 神経幹細胞 / 分化・増殖 / 自閉症 / 育児 / 記憶・学習
Research Abstract

Signaling through extracellular signal-regulated kinase (ERK) is important in multiple signal transduction networks in the central nervous system (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 employed 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 knockout (CKO) mice, in which Erk2 was abrogated specifically in the CNS, exhibited marked anomalies in multiple aspects of social behaviors related to facets of autism-spectrum disorders (ASD). 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.

Report

(4 results)
  • 2012 Annual Research Report   Final Research Report ( PDF )
  • 2011 Annual Research Report
  • 2010 Annual Research Report
  • Research Products

    (44 results)

All 2013 2012 2011 2010

All Journal Article (18 results) (of which Peer Reviewed: 15 results) Presentation (20 results) (of which Invited: 1 results) Book (4 results) Patent(Industrial Property Rights) (2 results) (of which Overseas: 1 results)

  • [Journal Article] Co-administration of Hydrogen Gas as Part of the Carrier Gas Mixture Suppresses Neuronal Apoptosis and Subsequent Behavioral Deficits Caused by Neonatal Exposure to Sevoflurane in MiceAnesthesiology2013

    • Author(s)
      Yonamine R., Satoh Y., Kodama M., Araki Y., Kazama T
    • Journal Title

      Anesthesiology

      Volume: 118 (1) Issue: 1 Pages: 105-113

    • DOI

      10.1097/aln.0b013e318275146d

    • Related Report
      2012 Annual Research Report 2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] MAPKカスケード2013

    • Author(s)
      佐藤泰司 遠藤昌吾
    • Journal Title

      Clinical Neuroscience「神経系のMAPキナーゼ」

      Volume: Vol 31 Pages: 649-649

    • URL

      https://www.chugaiigaku.jp/modules/shop/index.php?main_page=product_info&products_id=1357&PHPSESSID=45c0649080e6cbc570e285dc7e914f81

    • Related Report
      2012 Final Research Report
  • [Journal Article] Mechanical allodynia but not thermal hyperalgesia is impaired in mice deficient for ERK2 in the central nervous system2012

    • Author(s)
      Otsubo Y., Satoh Y., Kodama M., Araki Y., Satomoto M., Sakamoto E., Pages G., Pouyssegur J., Endo S., Kazama T.
    • Journal Title

      PAIN

      Volume: 153 Issue: 11 Pages: 2241-2252

    • DOI

      10.1016/j.pain.2012.07.020

    • Related Report
      2012 Annual Research Report 2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Bilateral orbital inflammation following intravesical Bacille Calmette-Guerin (BCG) immunotherapy for bladder cancer.2012

    • Author(s)
      Takeuchi A., Taguchi M., Satoh Y., Ishida M., Takeuchi M
    • Journal Title

      Japanese J. Ophthalmology. Jpn J Ophthalmol

      Volume: 56 (2) Issue: 2 Pages: 187-189

    • DOI

      10.1007/s10384-012-0120-0

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Tbx1: identification of a 22q11.2 gene as a risk factor for autism spectrum disorder in a mouse model2011

    • Author(s)
      Hiramoto T., Kang G., Suzuki G., Satoh Y., Kucherlapati R., Watanabe Y., Hiroi N
    • Journal Title

      Hum Mol Genet

      Volume: 20 (24) Issue: 24 Pages: 4775-4785

    • DOI

      10.1093/hmg/ddr404

    • Related Report
      2012 Final Research Report 2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Neonatal desflurane exposure induces more robust neuroapoptosis than do isoflurane and sevoflurane and impairs working memory2011

    • Author(s)
      Kodama M., Satoh Y., Otsubo Y., Araki Y., Yonamine R., Masui K., Kazama T
    • Journal Title

      Anesthesiology

      Volume: 115 (5) Pages: 979-1002

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Protective Effect of Neurotrophic Agent T-817MA Against Inner Ear Barotrauma in the Guinea Pig2011

    • Author(s)
      Maekawa H., Matsunobu T., Satoh Y., Kurioka T., Nakamura A., Iwakami N., Shiotani A
    • Journal Title

      Journal of Pharmacological Sciences

      Volume: 117 Issue: 1 Pages: 67-70

    • DOI

      10.1254/jphs.11033SC

    • NAID

      10029896029

    • ISSN
      1347-8613, 1347-8648
    • Related Report
      2012 Final Research Report 2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Targeted gene transfer into rat facial muscles by nanosecond pulsed laser-induced stress waves2011

    • Author(s)
      Akihiro Kurita, Takeshi Matsunobu, Yasushi Satoh, Takahiro Ando, Shunichi Sato, Minoru Obara, Akihiro Shiotani
    • Journal Title

      Journal of Biomedical Optics

      Volume: 16 Issue: 9 Pages: 98002-98005

    • DOI

      10.1117/1.3628313

    • Related Report
      2012 Final Research Report 2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] ERK2 contributes to the control of social behaviors in mice2011

    • Author(s)
      Satoh Y., Endo S., Nakata T., Kobayashi Y., Yamada K., Ikeda T., Takeuchi A., Hiramoto T., Watanabe Y., Kazama T
    • Journal Title

      J. Neuroscience

      Volume: 31(33) Issue: 33 Pages: 11953-67

    • DOI

      10.1523/jneurosci.2349-11.2011

    • Related Report
      2012 Final Research Report 2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Deletion of ERK1 and ERK2 in the CNS causes cortical abnormalities and neonatal lethality: Erk1 deficiency enhances the impairment of neurogenesis in Erk2-deficient mice2011

    • Author(s)
      Satoh Y., Kobayashi Y., Takeuchi A., Pages G.., Pouyssegur J., Kazama T
    • Journal Title

      J. Neuroscience

      Volume: 31(3) Issue: 3 Pages: 1149-55

    • DOI

      10.1523/jneurosci.2243-10.2011

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Neonatal desflurane exposure induces more robust neuroapoptosis than do isoflurane and sevoflurane and impairs working memory2011

    • Author(s)
      Mitsuyoshi Kodama
    • Journal Title

      Anesthesiology

      Volume: 115 Issue: 5 Pages: 979-1002

    • DOI

      10.1097/aln.0b013e318234228b

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Deletion of ERK1 and ERK2 in the CNS causes cortical abnormalities and neonatal lethality : Erk1 deficiency enhances the impairment of neurogenesis in Erk2-deficient mice.2011

    • Author(s)
      Satoh Y.
    • Journal Title

      Joural of Neuroscience

      Volume: 31 Pages: 1149-1155

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] シナプスにおけるERKシグナリングの役割2010

    • Author(s)
      佐藤泰司、遠藤昌吾
    • Journal Title

      生体の科学

      Volume: Vol 61 Pages: 460-461

    • Related Report
      2012 Final Research Report
  • [Journal Article] 神経系におけるMEK1/2の機能2010

    • Author(s)
      佐藤泰司、遠藤昌吾
    • Journal Title

      生体の科学

      Volume: Vol 61 Pages: 462-463

    • Related Report
      2012 Final Research Report
  • [Journal Article] FRS2α regulates Erk levels to control a self-renewal target Hes1 and proliferation of FGF-responsive neural stem/progenitor cells2010

    • Author(s)
      Sato T, Shimazaki T, Naka H, Fukami S, Satoh Y., Okano H, Lax I, Schlessinger J, Gotoh N
    • Journal Title

      Stem Cells

      Volume: 28(9) Issue: 9 Pages: 1661-73

    • DOI

      10.1002/stem.488

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Transient degradation of myelin basic protein in the rat hippocampus following acute carbon monoxide poisoning2010

    • Author(s)
      Watanabe S, Matsuo H, Kobayashi Y, Satoh Y., Fujita M, Nakayama A, Aizawa Y, Shinomiya N, Suzuki S
    • Journal Title

      Neurosci Res.

      Volume: 68(3) Issue: 3 Pages: 232-40

    • DOI

      10.1016/j.neures.2010.07.2029

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Pulmonary blast injury in mice: a novel model for studying blast injury in the laboratory using laser-induced stress waves2010

    • Author(s)
      Satoh Y., Sato S., Saitoh D., Tokuno S., Hatano B., Shimokawaji T., Kobayashi H., Takishima K.
    • Journal Title

      Lasers Surg. Med

      Volume: 42(4) Issue: 4 Pages: 313-8

    • DOI

      10.1002/lsm.20899

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] FRS2α regulates Erk levels to control a self-renewal target Hes1 and proliferation of FGF-responsive neural stem/progenitor cells.2010

    • Author(s)
      Sato T.
    • Journal Title

      Stem Cells

      Volume: 28 Pages: 1661-1673

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Presentation] Deletion of hepatic ERK2 decreased the SERCA2 expressions, which can account for vascular oxidative stress and endothelial dysfunction in metabolic stress2013

    • Author(s)
      Adachi T., Nanba T., Satoh Y., Ayaori M., Shiraishi Y., Arai-Nakaya Y., Endo S., Hakuno D., Yada H., Isoda K.,Endo S., Kujiraoka T
    • Organizer
      11th International sumposium on mechanisms of vasolidation (MOVD 2013)
    • Place of Presentation
      チューリッヒ、スイス
    • Related Report
      2012 Final Research Report
  • [Presentation] 、動物実験によって暴かれた麻酔薬の未知の毒性-麻酔薬の神経発達への影響-2013

    • Author(s)
      佐藤泰司
    • Organizer
      シンポジウム「脳を護る」招待講演、日本麻酔科学会第60回学術集会
    • Place of Presentation
      札幌
    • Related Report
      2012 Final Research Report
  • [Presentation] Hepatic ERK suppresses endothelial dysfunction with the alleviation of hepatosteatosis and metabolic remodeling in mice fed high-fat and high-sucrose diet2012

    • Author(s)
      Kujiraoka T., Satoh Y., Ayaori M., Shiraishi Y., Nakaya Y., Endo S., Hakuno D., Isoda K., Adachi T
    • Organizer
      欧州心臓学会議2012(ESC2012)
    • Place of Presentation
      ミュンヘン、ドイツ
    • Related Report
      2012 Final Research Report
  • [Presentation] Hepatic ERK2 deficiency develops hepatosteatosis with decreased expression of SERCA2, which can account for metabolic remodeling and endothelial dysfunction2012

    • Author(s)
      Kujiraoka T., Satoh Y., Ayaori M., Shiraishi Y., Nakaya Y., Endo S., Hakuno D., Isoda K., Adachi T
    • Organizer
      米国心臓病学会議2012(AHA 2012)
    • Place of Presentation
      ロサンゼルス、米国
    • Related Report
      2012 Final Research Report
  • [Presentation] Mechanical allodynia but not thermal hyperalgesia is impaired in mice deficient for ERK2 in the central nervous system2012

    • Author(s)
      Otsubo Y., Satoh Y., Kodama M., Araki Y., Endo S, Kazama T
    • Organizer
      世界疼痛学会2012(IASP 2012)
    • Place of Presentation
      ミラノ、イタリア
    • Related Report
      2012 Final Research Report
  • [Presentation] セボフルラン研究の最前線2012

    • Author(s)
      佐藤泰司
    • Organizer
      日本麻酔科学会第59回学術集会 (アボット製薬/丸石製薬 ランチョンセミナー)
    • Place of Presentation
      神戸
    • Related Report
      2012 Final Research Report
  • [Presentation] セボフルラン研究の最前線2012

    • Author(s)
      佐藤泰司
    • Organizer
      日本麻酔科学会第59回学術集会
    • Place of Presentation
      神戸
    • Related Report
      2012 Annual Research Report
    • Invited
  • [Presentation] Mechanical allodynia but not thermal hyperalgesia is impaired in mice deficient for ERK2 in the central nervous system.2012

    • Author(s)
      Yukiko Otsubo
    • Organizer
      IASP
    • Place of Presentation
      Milan
    • Related Report
      2012 Annual Research Report
  • [Presentation] Hepatic ERK suppresses endothelial dysfunction with the alleviation of hepatosteatosis and metabolic remodeling in mice fed high-fat and high-sucrose diet.2012

    • Author(s)
      Takehiko Kujiraoka
    • Organizer
      ESC2012
    • Place of Presentation
      Munich
    • Related Report
      2012 Annual Research Report
  • [Presentation] Hepatic ERK2 deficiency develops hepatosteatosis with decreased expression of SERCA2, which can account for metabolic remodeling and endothelial dysfunction2012

    • Author(s)
      Takehiko Kujiraoka
    • Organizer
      AHA2012
    • Place of Presentation
      los Angels
    • Related Report
      2012 Annual Research Report
  • [Presentation] 発達期の脳と麻酔薬2011

    • Author(s)
      佐藤泰司
    • Organizer
      日本臨床麻酔学会第31回大会
    • Place of Presentation
      沖縄(招待講演)
    • Year and Date
      2011-11-03
    • Related Report
      2011 Annual Research Report
  • [Presentation] 発達期の脳とセボフルラン2011

    • Author(s)
      Mitsuyoshi Kodama
    • Organizer
      Neonatal desflurane exposure induces more robust neuroapoptosis than doisoflurane and sevoflurane and impairs working memory
    • Place of Presentation
      シカゴ(米国)
    • Year and Date
      2011-10-16
    • Related Report
      2011 Annual Research Report
  • [Presentation] 発達期の脳とセボフルラン2011

    • Author(s)
      佐藤泰司
    • Organizer
      日本小児麻酔学会第17回大会
    • Place of Presentation
      大阪(招待講演)
    • Year and Date
      2011-09-23
    • Related Report
      2011 Annual Research Report
  • [Presentation] Neonatal desflurane exposure induces more robust neuroapoptosis than do isoflurane and sevoflurane and impairs working memory2011

    • Author(s)
      Kodama M., Satoh Y., Otsubo Y., Araki Y., Yonamine R., Kazama T
    • Organizer
      第63回米国麻酔会議
    • Place of Presentation
      シカゴ、米国
    • Related Report
      2012 Final Research Report
  • [Presentation] Advanced Gene Transfer Into The Inner Ear by the Use of Lase Induced Stress Wave (LISW)2011

    • Author(s)
      Kurioka T, Matsunobu T, Kurita A, Kamide D, Satoh Y, Kanzaki S, Ando T, Akiyama T, Sato S, Shiotani A
    • Organizer
      34th MidWinter Meeting, Association for Research in Otolaryngology
    • Place of Presentation
      バルチモア、米国
    • Related Report
      2012 Final Research Report
  • [Presentation] Hepatic ERK protects from endothelial dysfunction with the suppression of hepatic steatosis in mice fed high-fat and high-sucrose diet2011

    • Author(s)
      Kujiraoka T., Satoh Y., Ayaori M, Hakuno D., Endo S., Niida T., Isoda K., Adachi T
    • Organizer
      第84回米国心臓協会学術集会
    • Place of Presentation
      オーランド, 米国
    • Related Report
      2012 Final Research Report
  • [Presentation] 発達期の脳と麻酔薬2011

    • Author(s)
      佐藤泰司
    • Organizer
      日本臨床麻酔学会第31回大会
    • Place of Presentation
      沖縄
    • Related Report
      2012 Final Research Report
  • [Presentation] 発達期の脳とセボフルラン(アボット製薬/丸石製薬 ランチョンセミナー)2011

    • Author(s)
      佐藤泰司
    • Organizer
      日本小児麻酔学会第17回大会
    • Place of Presentation
      大阪
    • Related Report
      2012 Final Research Report
  • [Presentation] 新生仔マウスへのセボフルラン麻酔は自閉症様行動を誘発する---小児麻酔と自閉症の関係を考える。Neonatal Exposure to Sevoflurane Induces Autistic-Like Behaviors in Mice2010

    • Author(s)
      佐藤泰司
    • Organizer
      第57回日本麻酔科学会
    • Place of Presentation
      福岡(招待講演)
    • Year and Date
      2010-06-03
    • Related Report
      2010 Annual Research Report
  • [Presentation] 新生仔マウスへのセボフルラン麻酔は自閉症様行動を誘発する---小児麻酔と自閉症の関係を考える Neonatal Exposure to Sevoflurane Induces Autistic-Like Behaviors in Mice2010

    • Author(s)
      佐藤泰司
    • Organizer
      日本麻酔科学会第57回学術集会
    • Place of Presentation
      福岡
    • Related Report
      2012 Final Research Report
  • [Book] Clinical Neuroscience2013

    • Author(s)
      佐藤泰司
    • Total Pages
      3
    • Publisher
      中外医学社
    • Related Report
      2012 Annual Research Report
  • [Book] Psychobiological aspects of stress: resilient life through successful allostasis. In: Post-Traumatic Stress Disorder(PTSD): Causes, Symptoms and Treatment2010

    • Author(s)
      Nibuya M., Tanaka T., Satoh Y., Nomura S
    • Publisher
      NOVA Science Publishers, New York
    • Related Report
      2012 Final Research Report
  • [Book] 生体の科学 別冊「シナプスをめぐるシグナリング」シナプスにおけるERKシグナリングの役割2010

    • Author(s)
      佐藤泰司
    • Publisher
      医学書院
    • Related Report
      2010 Annual Research Report
  • [Book] 生体の科学 別冊「シナプスをめぐるシグナリング」神経系におけるMEK1/2の機能2010

    • Author(s)
      佐藤泰司
    • Publisher
      医学書院
    • Related Report
      2010 Annual Research Report
  • [Patent(Industrial Property Rights)] 全身麻酔薬と、水素とを組み合わせてなる、医薬2013

    • Inventor(s)
      風間富栄、佐藤泰司、与那嶺龍二
    • Industrial Property Rights Holder
      丸石製薬株式会社
    • Filing Date
      2013-05-30
    • Related Report
      2012 Final Research Report
    • Overseas
  • [Patent(Industrial Property Rights)] 全身麻酔薬と、水素とを組み合わせてなる、医薬2012

    • Inventor(s)
      風間富栄 他
    • Industrial Property Rights Holder
      丸石製薬株式会社
    • Industrial Property Rights Type
      特許
    • Filing Date
      2012-05-31
    • Related Report
      2012 Annual Research Report

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Published: 2010-08-23   Modified: 2019-07-29  

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