Molecular pharmacological analyses of CRTH2, the type II PGD2 receptor, as a molecule regulating emotional function

• Project/Area Number: 23790086
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Biological pharmacy
• Research Institution: Osaka University
• Principal Investigator: SHINTANI Norihito 大阪大学, 薬学研究科(研究院), 准教授 (10335367)
• Project Period (FY): 2011 – 2012
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2012: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2011: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
• Keywords: PGD2 / 情動機能 / 認知機能 / sickness behavior / 統合失調症 / うつ病 / ノルアドレナリン / ノックダウン / CRTH2 / 情動障害 / 認知機能障害 / 動物モデル / モノアミン / 精神疾患 / 一塩基多型

Research Abstract

Although accumulating evidences established stimulatory roles of prostanoid receptor CRTH2 in peripheral inflammation, its brain function is poorly understood. This study has revealed the specific involvement of brain CRTH2 in the emotional impairment in mice sickness behavior models, and its possible roles in the regulation of cognition both in experimental animals and human subjects. This study has also developed a knockdown system of CRTH2 etc., which will contribute to further molecular analysis of CRTH2 in the central nervous system.

Research Products

• [Journal Article] Central CRTH2, a Second Prostaglandin D2 Receptor, Mediates Emotional Impairment in the Lipopolysaccharide and Tumor-Induced Sickness Behavior Model (2014)
  • Author(s): Ryota Haba, Norihito Shintani,Yusuke Onaka, Takuya Kanoh, Hyper Wang, Risa Takenaga, Atsuko Hayata, Hiroyuki Hirai, Kin-ya Nagata, Masataka Nakamura, Atsushi Kasai, Ryota Hashimoto, Kazuki Nagayasu, Takanobu Nakazawa, Hitoshi Hashimoto, Akemichi Baba.
  • Journal Title: Journal of Neuroscience Volume: 34(7) Pages: 2514-2523
  • Peer Reviewed
• [Journal Article] Central CRTH2, a second prostaglandin D2 receptor, mediates emotional impairment in the lipopolysaccharide and tumor-induced sickness behavior model. (2014)
  • Author(s): Haba R, Shintani N, Onaka Y, Kanoh T, Wang H, Takenaga R, Hayata A, Hirai H, Nagata KY, Nakamura M, Kasai A, Haghi moto R, Nagayasu K, Nakazawa T, Hashimoto H, Baba A.
  • Journal Title: J Neurosci. Volume: 34 Issue: 7 Pages: 2514-2523
  • DOI: 10.1523/jneurosci.1407-13.2014
  • Peer Reviewed / Open Access
• [Journal Article] Lipopolysaccharide affects exploratory behaviors toward novel objects by impairing cognition and/or motivation in mice (2012)
  • Author(s): Ryota Haba, Norihito Shintani, Yusuke Onaka, Hyper Wang, Risa Takenaga, Atsuko Hayata, Akemichi Baba, Hitoshi Hashimoto
  • Journal Title: Possible role of activation of the central amygdala. Behavioral Brain Research Volume: 17 Pages: 412-431
  • Peer Reviewed
• [Journal Article] Lipopolysaccharide affects exploratory behaviors toward novel objects by imparing cognition and/or motivation in mice : Possible role of activation of the central amygdala (2012)
  • Author(s): Ryota Haba, et al
  • Journal Title: Behavioural Brain Research Volume: 228 Issue: 2 Pages: 423-431
  • DOI: 10.1016/j.bbr.2011.12.027
  • Peer Reviewed
• [Presentation] Anti-depressive phenotype in mice lacking prostanoid receptor DP2 (2014)
  • Author(s): Yusuke Onaka, Norihito Shintani, Hitoshi Hashimoto
  • Organizer: The 8th Seoul-Kyoto-Osaka Joint Symposium on Pharmaceutical Sciences for Young Scientists
  • Place of Presentation: 大阪大学銀杏会館三和ホール(大阪府)
  • Year and Date: 2014-06-11
• [Presentation] 情動障害モデルにおける行動変化にCRTH2の遺伝子欠損が与える影響 (2013)
  • Author(s): 尾中勇祐、新谷紀人、武永理佐、叶拓也、木野村元彦、羽場亮太、平井博之、永田欽也、中村正孝、早田敦子、笠井淳司、馬場明道、橋本均
  • Organizer: 第23回日本臨床精神神経薬理学会・第43回日本神経精神薬理学会合同年会
  • Place of Presentation: 沖縄コンベンションセンター(沖縄県)
  • Year and Date: 2013-10-25
• [Presentation] Altered cognitive function in mice lacking prostanoid receptor DP2 (2013)
  • Author(s): Yusuke Onaka, Takuya Kanoh, Norihito Shintani, Risa Takenaga, Ryota Haba, Atsuko Hayata, Atsushi Kasai, Hiroyuki Hirai, Kin-ya Nagata, Masataka Nakamura, Akemichi Baba, Hitoshi Hashimoto
  • Organizer: Neuro2013
  • Place of Presentation: 京都国際会議場(京都府)
  • Year and Date: 2013-06-22
• [Presentation] プロスタグランジンD2受容体サブタイプDP2 (CRTH2)の脳機能 (2013)
  • Author(s): 橋本均、新谷紀人、羽場亮太、尾中勇祐
  • Organizer: GPCR研究会2013
  • Place of Presentation: 日本科学未来館(東京都)
  • Year and Date: 2013-05-11
• [Presentation] プロスタノイド受容体CRTH2のsickness behavior発現における役割 (2013)
  • Author(s): 新谷紀人、羽場亮太、尾中勇祐、武永理佐、叶拓也、平井博之、永田欽也、中村正孝、早田敦子、馬場明道、橋本均
  • Organizer: 日本薬学会第113年会
  • Place of Presentation: パシフィコ横浜(神奈川県)
  • Year and Date: 2013-03-29
• [Presentation] プロスタノイド受容体CRTH2欠損マウスではMK-801による認知障害は認められない (2013)
  • Author(s): 叶拓也、新谷紀人、尾中勇祐、武永理佐、羽場亮太、早田敦子、平井博之、永田欽也、中村正孝、馬場明道、橋本均
  • Organizer: 第86回日本薬理学会年会
  • Place of Presentation: 福岡国際会議場(福岡県)
  • Year and Date: 2013-03-22
• [Presentation] 情動障害モデルにおける行動変化にCRTH2の遺伝子欠損が与える影響 (2013)
  • Author(s): 尾中 勇祐、他
  • Organizer: 第23回日本臨床精神薬理学会／第43回日本精神神経薬理学会
  • Place of Presentation: 沖縄県
• [Presentation] Altered cognitive function in mice lacking prostanoid receptor DP2 (2013)
  • Author(s): Yusuke Onaka et al.
  • Organizer: Neuro2013
  • Place of Presentation: Kyoto, Japan
• [Presentation] プロスタグランジンD2受容体サブタイプDP2 (CRTH2)の脳機能 (2013)
  • Author(s): 橋本 均、他
  • Organizer: 第10回GPCR研究会
  • Place of Presentation: 東京都
• [Presentation] プロスタノイド受容体CRTH2を欠損したマウスではMK-801で誘発される認知機能障害が消失する (2013)
  • Author(s): 叶 拓也、他
  • Organizer: 第86回 日本薬理学会年会
  • Place of Presentation: 福岡県
• [Presentation] Selective involvement of prostanoid receptor CRTH2 in depression-like behaviors (2012)
  • Author(s): Norihito Shintani, Yusuke Onaka, Risa Takenaga, Takuya Kanoh, Ryota Haba, Atsuko Hayata, Hiroyuki Hirai, Kin-ya Nagata, Masataka Nakamura, Akemichi Baba, Hitoshi Hashimoto
  • Organizer: The 11th Biennial Meeting of the Asian Pacific Society for Neurochemistry, The 55th Annual Meeting of the Japanese Society for Neurochemistry
  • Place of Presentation: 神戸国際会議場(兵庫県)
  • Year and Date: 2012-10-01
• [Presentation] 情動障害モデルの行動異常におけるプロスタノイド受容体CRTH2の関与 (2012)
  • Author(s): 尾中勇祐、新谷紀人、武永理佐、叶拓也、羽場亮太、平井博之、永田欽也、中村正孝、早田敦子、馬場明道、橋本均
  • Organizer: 第11回次世代を担う若手ファーマバイオフォーラム2012
  • Place of Presentation: 九州大学病院キャンパスコラボI(福岡県)
  • Year and Date: 2012-09-16
• [Presentation] 担ガン動物の行動異常発現におけるプロスタノイド受容体CRTH2の役割 (2012)
  • Author(s): 武永理佐、尾中勇祐、叶拓也、新谷紀人、羽場亮太、平井博之、永田欽也、中村正孝、早田敦子、馬場明道、橋本均.
  • Organizer: 次世代を担う創薬・医療薬理シンポジウム2012
  • Place of Presentation: 神戸学院大学(兵庫県)
  • Year and Date: 2012-09-01
• [Presentation] 情動障害モデルの行動異常におけるプロスタノイド受容体CRTH2の関与 (2012)
  • Author(s): 尾中 勇祐、他
  • Organizer: 第11回次世代を担う若手ファーマバイオフォーラム２０１２
  • Place of Presentation: 福岡県
• [Presentation] Selective involvement of prostanoid receptor CRTH2 in depression-like behaviors (2012)
  • Author(s): Norihito Shintani et al.
  • Organizer: The 11th Biennial Meeting of the Asian Pacific Society for Neurochemistry, The 55th Annual Meeting of the Japanese Society for Neurochemistry
  • Place of Presentation: Hyogo, Japan
• [Presentation] Specific roles of prostanoid receptor CRTH2 in LPS-induced sickness behaviors (2011)
  • Author(s): Ryota Haba, Norihito Shintani, Yusuke Onaka, Risa Takenaga, Atsuko Hayata, Hiroyuki Hirai, Kin-ya Nagata, Masataka Nakamura, Akemichi Baba、Hitoshi Hashimoto
  • Organizer: The 32nd Naito Conference
  • Place of Presentation: 八ヶ岳ロイヤルホテル(山梨県)
  • Year and Date: 2011-09-27
• [Presentation] Lipopolysaccharideによって誘発される新奇物体への探索行動の減少におけるcyclooxygenase-2の選択的な関与 (2011)
  • Author(s): 武永理佐、羽場亮太、尾中勇祐、新谷紀人、早田敦子、馬場明道、橋本均
  • Organizer: 次世代を担う創薬・医療薬理シンポジウム2011
  • Place of Presentation: 北里大学薬学部コンベンションホール(東京都)
  • Year and Date: 2011-08-31
• [Presentation] LPSによる扁桃体中心核の活性化におけるCRTH2の関与メカニズム (2011)
  • Author(s): 羽場亮太、新谷紀人、尾中勇祐、武永理佐、早田敦子、馬場明道、橋本均
  • Place of Presentation: ウィンク愛知(愛知県)
  • Year and Date: 2011-07-08
• [Presentation] LPSによる扁桃体中心核の活性化におけるCRTH2の関与メカニズム (2011)
  • Author(s): 羽場 亮太、他
  • Organizer: 第119回日本薬理学会近畿部会
  • Place of Presentation: 愛知県
• [Presentation] Lipopolysaccharideによって誘発される新奇物体への探索行動の減少における cyclooxygenase-2の選択的な関与 (2011)
  • Author(s): 武永 理佐、他
  • Organizer: 次世代を担う創薬・医療薬理シンポジウム2011
  • Place of Presentation: 東京都
• [Presentation] Specific roles of prostanoid receptor CRTH2 in LPS-induced sickness behaviors (2011)
  • Author(s): Ryota Haba et al.
  • Organizer: The 32nd Naito Conference
  • Place of Presentation: 山梨県
• [Presentation] 担ガン動物の行動異常発現におけるプロスタノイド受容体CRTH2の役割
  • Author(s): 武永 理佐、他
  • Organizer: 次世代を担う創薬・医療薬理シンポジウム2012
  • Place of Presentation: 兵庫県
• [Remarks] 執筆者自身による研究論文レビュー(BioMedサーカスcom).新谷紀人、羽場亮太、橋本 均、馬場明道.炎症時の情動関連障害はプロスタノイド受容体CRTH2を介して発現する
  • URL: http://biomedcircus.com/paper_03_27.html
• [Remarks] 執筆者自身による研究論文レビュー（BioMedサーカスcom）
  • URL: http://biomedcircus.com/paper_03_27.html
• [Remarks]
  • URL: http://molpharm.umin.jp/