Treatment strategy for hypoxic-ischemic encephalopathy by regulation of prostaglandins bioactivities

• Project/Area Number: 25870677
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Pediatrics; Embryonic/Neonatal medicine
• Research Institution: Saitama Medical University
• Principal Investigator: Yoshikawa Keisuke 埼玉医科大学, 医学部, 講師 (10435860)
• Project Period (FY): 2013-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2014: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2013: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 興奮毒性 / プロスタグランジン / 神経細胞死

Outline of Final Research Achievements

Hypoxic-ischemic encephalophaty(HIE) is a brain disorder caused by excitotoxicity induced neuronal death and is responsible for neonatal death, cerebral palsy and developmental disorder. Prostaglandins (PGs) are known to be upregulated in the excitotoxic insulted brain. We demonstrated that PGD2 and PGF2alpha are involved in the excitotoxicity induced neuronal death. An inhibitory treatment of PGD2 and PGF2alpha production is an important therapeutic strategy for brain damage induced by excitotoxic mechanisms such as HIE.

Research Products

• [Journal Article] Excitotoxicity-induced prostaglandin D2 production induces sustained microglial activation and delayed neuronal death. (2017)
  • Author(s): Iwasa K, Yamamoto S, Yagishita S, Maruyama K, Yoshikawa K.
  • Journal Title: J Lipid Res. Volume: 58 Issue: 4 Pages: 649-655
  • DOI: 10.1194/jlr.m070532
  • Peer Reviewed / Open Access
• [Journal Article] Treatment of intermittent hypoxia increases phosphorylated tau in the hippocampus via biological processes common to aging. (2017)
  • Author(s): Yagishita S, Suzuki S, Yoshikawa K, Iida K, Hirata A, Suzuki M, Takashima A, Maruyama K, Hirasawa A, Awaji T.
  • Journal Title: Mol Brain Volume: 10 Issue: 1 Pages: 2-2
  • DOI: 10.1186/s13041-016-0282-7
  • NAID: 120005971848
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] プロスタグランジンF2 FPレセプター阻害は多発性硬化症モデルマウスの神経脱髄と運動障害を改善する (2015)
  • Author(s): 岩佐健介、山本梓司、高橋茉莉香、鈴木星也、柳下聡介、淡路健雄、丸山敬、吉川圭介
  • Journal Title: 脂質生化学研究 Volume: ５７ Pages: 85-88
• [Journal Article] 脂質メディエーター・環状ホスファチジン酸の変形性関節症と多発性硬化症への効果とその医療応用への展望 (2015)
  • Author(s): 後藤真里、吉川圭介、塚原涼子、室伏きみ子
  • Journal Title: 脂質栄養学 Volume: ２４ Pages: 41-51
  • NAID: 130005068519
• [Journal Article] Prostaglandin F2α FP receptor inhibitor reduces demyelination and motor dysfunction in a cuprizone-induced multiple sclerosis mouse model (2014)
  • Author(s): Iwasa K, Yamamoto S, Takahashi M, Suzuki S, Yagishita S, Awaji T, Maruyama K, Yoshikawa K
  • Journal Title: Prostaglandins, Leukotrienes and Essential Fatty Acids Volume: 91 Issue: 5 Pages: 175-182
  • DOI: 10.1016/j.plefa.2014.08.004
  • Peer Reviewed / Open Access
• [Journal Article] Cyclic phosphatidic acid treatment suppress cuprizone-induced demyelination and motor dysfunction in mice (2014)
  • Author(s): Yamamoto S, Gotoh M, Kawamura Y, Yamashina K, Yagishita S, Awaji T, Tanaka M, Maruyama K, Murakami-Murofushi K, Yoshikawa K.
  • Journal Title: European Journal of Pharmacology Volume: 741 Pages: 17-24
  • DOI: 10.1016/j.ejphar.2014.07.040
  • Peer Reviewed / Open Access
• [Journal Article] Excitotoxicity-induced immediate surge in hippocampal prostanoid production has latent effects that promote chronic progressive neuronal death. (2013)
  • Author(s): Yoshikawa K., Kita Y., Furukawa A., Kawamura N., Hasegawa-Ishii S., Chiba Y., Takei S., Maruyama K., Shimizu T., Shimada A.
  • Journal Title: Prostaglandins Leukot Essent Fatty Acids. Volume: 88(5) Issue: 5 Pages: 373-381
  • DOI: 10.1016/j.plefa.2013.02.007
  • Peer Reviewed
• [Presentation] Cyclic phosphatidic acid derivative is a novel drug candidate for multiple sclerosis (2017)
  • Author(s): K. Yoshikawa, S. Yamamoto, M Yamashina, M. K Iwasa, Gotoh, T, M. Suzuki, K. Maruyama, K. Murakami-Murofushi
  • Organizer: 第90回日本薬理学会年会
  • Place of Presentation: 長崎
  • Year and Date: 2017-03-15
• [Presentation] 食事性肥満の世代間伝達が認知機能に及ぼす影響 (2017)
  • Author(s): 吉川圭介、江口寧々、岩佐健介、山本梓司、丸山敬、平澤明
  • Organizer: 第26回神経行動薬理若手研究者の集い
  • Place of Presentation: 福岡
• [Presentation] 内在性リン酸化タウ増加モデルのマイクロアレイ解析 (2016)
  • Author(s): 栁下聡介、鈴木星也、吉川圭介、飯田桂子、平田理子、鈴木正彦、高島明彦、丸山敬、平澤明、淡路健雄
  • Organizer: 第35回日本認知症学会
  • Place of Presentation: 東京
  • Year and Date: 2016-12-11
• [Presentation] Cyclic phosphatidic acid derivative is a novel drug candidate for multiple sclerosis (2016)
  • Author(s): K. Yoshikawa, S. Yamamoto, M. Gotoh, T. Shimizu, M. Hashimoto, K. Yamashina, M. Suzuki, K. Maruyama, K. Murakami-Murofushi
  • Organizer: 14th Meeting of The Asian-pacific society for Neurochemistry
  • Place of Presentation: Kuala Lumpur, Malaysia
  • Year and Date: 2016-08-26
  • Int'l Joint Research
• [Presentation] 多発性硬化症の新規治療薬候補・環状ホスファチジン誘導体 (2016)
  • Author(s): 山本梓司、清水嘉文、後藤真里、橋本真歩、山科孝太、岩佐健介、丸山敬、室伏きみ子、吉川圭介
  • Organizer: 第58回日本脂質生化学会
  • Place of Presentation: 秋田
  • Year and Date: 2016-06-09
• [Presentation] 神経変性疾患における脂質メディエーターの作用機序と創薬的展望 (2016)
  • Author(s): 吉川圭介
  • Organizer: 神経行動薬理若手研究者の集い
  • Place of Presentation: ソニックシティホール（埼玉県さいたま市）
  • Year and Date: 2016-03-08
  • Invited
• [Presentation] Cyclic phosphatidic acid treatment suppress cuprizone-induced demyelination and motor dysfunction (2015)
  • Author(s): Yamamoto S, Gotoh M, Kawamura Y, Yamashina K, Yagishita S, Awaji T, Tanaka M, Maruyama K, Murakami-Murofushi K, Yoshikawa K
  • Organizer: European committee for treatment and research in Multiple Sclerosis
  • Place of Presentation: バルセロナ、スペイン
  • Year and Date: 2015-10-07 – 2015-10-10
• [Presentation] Cyclic phosphatidic acid treatment suppress cuprizone-induced demyelination and motor dysfunction (2015)
  • Author(s): Yamamoto S, Gotoh M, Kawamura Y, Yagishita S, Awaji T, Tanaka M, Maruyama K, Murakami-Murofushi K, Yoshikawa K
  • Organizer: ECTRIMS (European committee for treatment and research in Multiple Sclerosis)
  • Place of Presentation: Barcelona, Spain
  • Year and Date: 2015-10-07
  • Int'l Joint Research
• [Presentation] 口腔内細菌の多発性硬化症への影響 (2015)
  • Author(s): 吉川圭介、山本梓司、山科孝太、岩佐健介、丸山敬、田名求
  • Organizer: 第132回日本薬理学会関東支部会
  • Place of Presentation: 明海大学（千葉県浦安市）
  • Year and Date: 2015-07-04
• [Presentation] プロスタグランジンF2alpha; FPレセプター阻害は多発性硬化症モデルマウスの神経脱髄と運動障害を改善する (2015)
  • Author(s): 岩佐健介、山本梓司、高橋茉莉香、鈴木星也、柳下聡介、淡路健雄、丸山敬、吉川圭介
  • Organizer: 第57回日本脂質生化学会
  • Place of Presentation: 一橋大学（東京都千代田区）
  • Year and Date: 2015-05-28
• [Presentation] Prostaglandin F2FP receptor inhibitor reduces demyelination and motor dysfunction in a cuprizone-induced multiple sclerosis mouse model (2015)
  • Author(s): 岩佐健介、山本梓司、高橋茉莉香、鈴木星也、柳下聡介、淡路健雄、丸山敬、吉川圭介
  • Organizer: 第88回日本薬理学会年会
  • Place of Presentation: 名古屋国際会議場（名古屋市）
  • Year and Date: 2015-03-18 – 2015-03-20
• [Presentation] Prostaglandin F2α FP receptor inhibitor reduce demyelination and motor dysfunction in a cuprizone-induced multiple sclerosis mouse model (2015)
  • Author(s): Iwasa K, Yamamoto S, Takahashi M, Suzuki S, Yagishita S, Awaji T, Maruyama K, Yoshikawa K
  • Organizer: Phospholipase and other lipid mediators 2015
  • Place of Presentation: 京王プラザホテル（東京都新宿区）
  • Year and Date: 2015-02-10 – 2015-02-12
• [Presentation] Cyclic phosphatidic acid treatment suppress cuprizone-induced demyelination and motor dysfunction (2015)
  • Author(s): Yamamoto S, Gotoh M, Kawamura Y, Yamashina K, Yagishita S, Awaji T, Tanaka M, Maruyama K, Murakami-Murofushi K, Yoshikawa K
  • Organizer: Phospholipase and other lipid mediators 2015
  • Place of Presentation: 京王プラザホテル（東京都新宿区）
  • Year and Date: 2015-02-10 – 2015-02-12
• [Presentation] Prostaglandin F2a FP receptor inhibitor suppress demyelination and motor dysfunction in a cuprizone-induced multiple sclerosis mouse model (2014)
  • Author(s): Yoshikawa K, Iwasa K, Yamamoto S, Maruyama K
  • Organizer: NEUROSCIENCE
  • Place of Presentation: ワシントンDC、アメリカ合衆国
  • Year and Date: 2014-11-15 – 2014-11-19
• [Presentation] Effect of extract X for working memory performance and amyloid-β protein in mice (2014)
  • Author(s): 岩佐健介、譚慧、緑川沙也華、根本みく、水嶋麻未、吉川圭介、清水邦義、丸山敬
  • Organizer: 第87回日本薬理学会年会
  • Place of Presentation: 仙台市
• [Presentation] 環状ホスファチジン酸による中枢性脱髄抑制効果 (2014)
  • Author(s): 山本梓司、川村勇樹、後藤真里、吉川圭介、室伏きみ子、丸山敬
  • Organizer: 第87回日本薬理学会年会
  • Place of Presentation: 仙台市
• [Presentation] 脱髄疾患におけるアラキドン酸カスケードの寄与 (2013)
  • Author(s): 吉川圭介、Sara Palumbo、山本梓司、高橋茉莉香、丸山敬、Francesca Bosetti
  • Organizer: 第55回日本脂質生化学会
  • Place of Presentation: 宮城県松島町
• [Presentation] 脱髄疾患におけるアラキドン酸カスケードの寄与 (2013)
  • Author(s): 山本梓司、吉川圭介、Sara Palumbo、Francesca Bosetti、丸山敬
  • Organizer: 平成25年度日本生化学会関東支部会
  • Place of Presentation: 甲府市
• [Presentation] 脱髄疾患におけるアラキドン酸カスケードの生理活性 (2013)
  • Author(s): 山本 梓司, 吉川 圭介, Sara Palumbo, 丸山 敬, Francesca Bosetti
  • Organizer: 第86回日本生化学会大会
  • Place of Presentation: 横浜市
• [Presentation] 環状ホスファチジン酸による中枢性脱髄抑制効果 (2013)
  • Author(s): 山本梓司、吉川圭介、川村勇樹、後藤真理、室伏きみ子、丸山敬
  • Organizer: 第129回日本薬理学会関東支部会
  • Place of Presentation: 東京都
• [Patent(Industrial Property Rights)] 脱髄疾患治療薬 (2014)
  • Inventor(s): 室伏きみ子、後藤真里、丸山敬、吉川圭介、山本梓司
  • Industrial Property Rights Holder: 国立大学法人お茶の水女子大学、学校法人埼玉医科大学
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2013-012859
  • Filing Date: 2014-01-28
  • Overseas
• [Patent(Industrial Property Rights)] タウタンパク質のリン酸化が亢進された非ヒトモデル動物の製造方法 (2013)
  • Inventor(s): 栁下聡介，鈴木正彦，淡路健雄，吉川圭介，丸山敬，鈴木星也
  • Industrial Property Rights Holder: 栁下聡介，鈴木正彦，淡路健雄，吉川圭介，丸山敬，鈴木星也
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2013-130358
  • Filing Date: 2013-06-21
• [Funded Workshop] ECTRIMS (European committee for treatment and research in Multiple Sclerosis) (2015)
  • Place of Presentation: Barcelona, Spain
  • Year and Date: 2015-10-07