Comparative studies on the risk of sensorimotor gating deficits in animal models of early amino acid/protein malnutrition.

• Project/Area Number: 22380078
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Food science
• Research Institution: Kyushu University
• Principal Investigator: FURUYA Shigeki 九州大学, 農学研究院, 教授 (00222274)
• Co-Investigator(Kenkyū-buntansha): TOMONAGA Shozo 京都大学, 農学研究科, 助教 (00552324)
• Project Period (FY): 2010 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥16,510,000 (Direct Cost: ¥12,700,000、Indirect Cost: ¥3,810,000); Fiscal Year 2012: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000); Fiscal Year 2011: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000); Fiscal Year 2010: ¥10,530,000 (Direct Cost: ¥8,100,000、Indirect Cost: ¥2,430,000)
• Keywords: 栄養学 / 脳神経疾患 / 食品 / アミノ酸 / セリン / 発達期 / 低栄養 / 精神疾患 / 統合失調症 / 行動解析 / マウスモデル

Research Abstract

Epidemiological studies provide evidence showing that early malnutrition may increase the risk ofschizophrenia. The goal of the present study is to clarify effects of early amino acid/protein malnutrition on sensorimotor gating deficits, which have relevance to schizophrenia. We examined prepulse inhibition (PPI) of two different mouse models of early nutritional deficiencies, which recapture genetic serine deficiency and prenatal protein malnutrition. PPI is an operational measure of sensorimotor gating that is impaired in both human patients and rodent models of schizophrenia. We observed that in adulthood the serene deficiency model and the protein malnutrition model exhibited reduced levels of PPI in a gender specific manner. These results suggest that both serine deficiency and protein malnutrition during early developmental stages increase the risk of sex-dependent sensorimotor gating deficits

Research Products

• [Journal Article] D-Serine in glia and neuronsderives from 3-phosphoglycerate dehydrogenase (2013)
  • Author(s): Ehmsen, J.T., Ma, T.M., Sason, H., Rosenberg,D., Ogo, T., Furuya, S., Snyder, S.H.,Wolosker, H.
  • Journal Title: J. Neurosci. Volume: 33 Pages: 12464-12469
• [Journal Article] erinedeficiency caused by genetic Phgdh deletionleads to robust induction of 4E-BP1 andsubsequent repression of translation initiationin the central nervous system (2013)
  • Author(s): Sayano, T., Kawakami, Y., Kusada, W.,Suzuki, T., Kawano, Y., Watanabe, A.,Takashima, K., Arimoto, Y., Esaki, K., Wada,A., Yoshizawa, F., Watanabe, M., Okamoto,M., Hirabayashi, Y., Furuya, S
  • Journal Title: FEBS J Volume: 280 Pages: 1502-1517
• [Journal Article] Deficiency of schnurri-2, an MHC enhancer binding protein, induces mild chronic inflammation in the brain and confers molecular, neuronal, and behavioral phenotypes related to schizophrenia. (2013)
  • Author(s): Takao K, Kobayashi K, Hagihara H, Ohira K, Shoji H, Hattori S, Koshimizu H, Umemori J, Toyama K, Nakamura HK, Kuroiwa M, Maeda J, Atsuzawa K, Esaki K, Yamaguchi S, Furuya S, Takagi T, Walton NM, Hayashi N, Suzuki H, Higuchi M, Usuda N, Suhara T, Nishi A, Matsumoto M, Ishii S, Miyakawa T.
  • Journal Title: Neuropsychopharmacology Volume: 38(8) Issue: 8 Pages: 1409-25
  • DOI: 10.1038/npp.2013.38
  • Peer Reviewed / Open Access
• [Journal Article] Increased tyrosinein the brain and serum of mice by orallyadministering dipeptide SY (2013)
  • Author(s): Esaki, K., Ohmori, T., Maebuchi, M., Nakamori,T., Ohshima, T., Furuya, S.
  • Journal Title: Biosci. Biotech.Biochem Volume: 77 Pages: 847-849
• [Journal Article] Serine deficiency caused by genetic Phgdh deletion leads to robust induction of 4E-BP1 and subsequent repression of translation initiation in the central nervous system. (2013)
  • Author(s): Tomoko Sayano
  • Journal Title: FEBS J. Volume: 280 Issue: 6 Pages: 1502-1517
  • DOI: 10.1111/febs.12146
  • Peer Reviewed
• [Journal Article] Increased tyrosine in the brain and serum of mice by orally administering dipeptide SY. (2013)
  • Author(s): Kayoko Esaki
  • Journal Title: Biosci. Biotechnol. Biochem. Volume: 77
  • Peer Reviewed
• [Journal Article] Type 1 diabetes mellitus in miceincreases hippocampal D-serine in the acutephase after streptozotocin injection (2012)
  • Author(s): Suzuki, M., Sasabe, J., Furuya, S., Hamase, K.,Aiso, S
  • Journal Title: Brain Res Volume: 1466 Pages: 167-176
• [Journal Article] 大豆タンパク質由来ジペプチドが中枢神経系に及ぼす作用の神経化学的評価 (2012)
  • Author(s): 江崎加代子,古屋茂樹
  • Journal Title: 大豆タンパク質研究 Volume: 15
• [Journal Article] Type 1 diabetes mellitus in mice increases hippocampal D-serine in the acute phase after streptozotocin injection. (2012)
  • Author(s): Masataka Suzuki
  • Journal Title: Brain Res. Volume: 1466 Pages: 167-176
  • DOI: 10.1016/j.brainres.2012.05.042
  • Peer Reviewed
• [Journal Article] 3-ホスホグリセリン酸脱水素酵素欠損症. (2012)
  • Author(s): 古屋 茂樹
  • Journal Title: 別冊 日本臨牀 新領域別症候群シリーズ「先天代謝異常症候群（第2版）病因･病態研究，診断･治療の進歩」 Volume: 19 Pages: 327-331
• [Journal Article] ホスホセリンアミノトランスフェラーゼ欠損症. (2012)
  • Author(s): 古屋 茂樹
  • Journal Title: 別冊 日本臨牀 新領域別症候群シリーズ「先天代謝異常症候群（第2版）病因･病態研究，診断･治療の進歩」 Volume: 19 Pages: 332-334
• [Journal Article] ホスホセリンホスファターゼ欠損症. (2012)
  • Author(s): 古屋 茂樹
  • Journal Title: 別冊 日本臨牀 新領域別症候群シリーズ「先天代謝異常症候群（第2版）病因･病態研究，診断･治療の進歩」 Volume: 19 Pages: 335-337
• [Journal Article] Soy peptide ingestionincreases neuroactive amino acids in the adultbrain of wild-type and genetically engineeredserine-deficient mice. (2011)
  • Author(s): Esaki, K., Kokido, T., Ohmori, T., Tsukino, M.,Ohshima, T., Furuya, S
  • Journal Title: J. Nutr. Food Sci Volume: 1 Pages: 109-109
• [Journal Article] Soy peptide as functional food component (2011)
  • Author(s): Maebuchi, M., Yamaguchi, N., and Furuya, S
  • Journal Title: Medicine and Biology Volume: 155 Pages: 566-576
  • NAID: 40018949832
• [Journal Article] セリン合成不全によるスフィンゴ脂質恒常性破綻と末梢神経障害 (2011)
  • Author(s): 古屋茂樹
  • Journal Title: 糖尿病関連病態. アミノ酸研究 Volume: 5 Pages: 15-20
• [Journal Article] Soy peptide ingestion increases neuroactive amino acids in the adultbrain of wild-type and genetically engineered serine-deficient mice (2011)
  • Author(s): Kayoko Esaki
  • Journal Title: J.Nutr.Food Sci. Volume: 1 Issue: 04
  • DOI: 10.4172/2155-9600.1000109
  • Peer Reviewed
• [Journal Article] セリン合成不全によるスフィンゴ脂質恒常性破綻と末梢神経障害・糖尿病関連病態 (2011)
  • Author(s): 古屋茂樹
  • Journal Title: アミノ酸研究 Volume: 5 Pages: 15-20
• [Journal Article] 遺伝性セリン合成不全疾患モデルマウスの脳内遊離アミノ酸組成に及ぼす大豆ペプチド摂取効果の定量的検討 (2010)
  • Author(s): 古屋 茂樹
  • Journal Title: 大豆タンパク質研究 Volume: 13 Pages: 109-115
  • NAID: 40018765262
• [Journal Article] Brain-specific Phgdh deletion reveals a pivotalrole for L-serine biosynthesis in controlling thelevel of D-serine, an NMDA receptorco-agonist, in adult brain (2010)
  • Author(s): Yang, JH., Wada, A., Yoshida, K., Miyoshi, Y.,Sayano, T., Esaki, K., Kinoshita, O.M.,Tomonaga, S., Azuma, N., Watanabe, M.,Hamase, K., Zaitsu, K., Machida, T., Messing,A., Itohara, S., Hirabayashi, Y., Furuya, S
  • Journal Title: J. Biol. Chem. Volume: 285 Pages: 41380-41390
• [Journal Article] アミノ酸研究の最前線I (2010)
  • Author(s): 古屋 茂樹
  • Journal Title: 外科と代謝・栄養 Volume: 44 Pages: 65-71
  • NAID: 10026098532
• [Journal Article] Brain-specific Phgdh deletion reveals a pivotal role for L-serine biosynthesis in controlling the level of D-serine, an NMDA receptor co-agonist in adult brain (2010)
  • Author(s): Yang, et al
  • Journal Title: Journal of Biological Chemistry Volume: 285 Pages: 41380-41390
  • Peer Reviewed
• [Presentation] 統合失調症関連エンドフェノタイプ発症に及ぼす妊娠期及び授乳期低タンパク質栄養の影響 (2013)
  • Author(s): 市瀬嵩志, 小河匡, 安尾しのぶ, 古屋茂樹
  • Organizer: 2013 年度農芸化学会大会
  • Place of Presentation: 仙台市(東北大学)
  • Year and Date: 2013-03-26
• [Presentation] 統合失調症関連エンドフェノタイプ発症に及ぼす妊娠期及び授乳期低タンパク質栄養の影響 (2013)
  • Author(s): 市瀬 嵩志
  • Organizer: 2013年度農芸化学会大会
  • Place of Presentation: 仙台市（東北大学）
• [Presentation] L-セリン生合成系による生体機能制御,第85回日本生化学会大会シンポジウム1S04 (2012)
  • Author(s): 古屋茂樹
  • Organizer: アミノ酸の新規機能と病態連関のニューフロンティア
  • Place of Presentation: 福岡国際会議場
  • Year and Date: 2012-12-14
• [Presentation] セリン欠乏による細胞毒性新奇スフィンゴ脂質の蓄積:in vivo 及びin vitroにおける解析 (2012)
  • Author(s): 江崎 加代子, 佐矢野智子, 平林義雄,古屋 茂樹
  • Organizer: 第6回日本アミノ酸学会学術大会
  • Place of Presentation: 松戸市(千葉大学)
  • Year and Date: 2012-09-28
• [Presentation] セリン欠乏が惹起する異常スフィンゴ脂質産生による遺伝子発現並びに細胞形態変化 (2012)
  • Author(s): 佐矢野智子, 江崎加代子, 濱野桃子,鵜殿美弥子, 片倉喜範,加藤久典,平林義雄, 古屋茂樹
  • Organizer: 第6回日本アミノ酸学会学術大会
  • Place of Presentation: 松戸市(千葉大学
  • Year and Date: 2012-09-28
• [Presentation] Deficiency of Schnurri-2,an MHC enhancer binding protein, induces amild chronic inflammation in the brain andconfers molecular, neuronal and behavioralphenotypes related to schizophrenia (2012)
  • Author(s): Keizo Takao, Katsunori Kobayashi, KayokoEsaki, Shigeki Furuya, Tsuyoshi Takagi, NoahWalton, Nobuhiro Hayashi, Hidenori Suzuki,Mitsuyuki Matsumoto, Shunsuke Ishii,Tsuyoshi Miyakawa
  • Organizer: 29th CINP World Congress of Neuropsycho-pharmacology
  • Place of Presentation: Vancouver,Canada
  • Year and Date: 2012-06-05
• [Presentation] セリン欠乏による神経毒性異常スフィンゴ脂質の蓄積:in vivo 及びin vitroにおける解析 (2012)
  • Author(s): 江崎 加代子, 佐矢野智子, 平林義雄,古屋 茂樹
  • Organizer: 第66回日本栄養・食糧学会大会
  • Place of Presentation: 仙台市
  • Year and Date: 2012-05-19
• [Presentation] Deficiency of Schnurri-2, an MHCenhancer binding protein, induces mild chronicinflammation in the brain and confersmolecular, neuronal, and behavioral phenotypesrelated to schizophrenia (2012)
  • Author(s): Keizo Takao, Katsunori Kobayashi, HideoHagihara, Koji Ohira, Keiko Toyama, HirotakaShoji, Hironori K Nakamura, Kayoko Esaki,Shigeki Furuya, Tsuyoshi Takagi, Noah Walton,Nobuhiro Hayashi, Hidenori Suzuki, MitsuyukiMatsumoto, Shunsuke Ishii, TsuyoshiMiyakaw
  • Organizer: Genes, Brain, andBehavior 2012 (14th Annual Meeting of theInternational Behavioural and Neural GeneticsSociety)
  • Place of Presentation: Boulder, CO, USA
  • Year and Date: 2012-05-18
• [Presentation] Deficitsin sensorimotor gating and social behavior inbrain-specific Phgdh knockout mice (2012)
  • Author(s): Tadashi Ogo, Akihiro Watanabe, ShozoTomonaga, Yoshio Hirabayashi, Keizo Takao,Tsuyoshi Miyakawa, Shigeki Furuya
  • Organizer: The 11th Biennial Meeting of the Asian Pacific Societyfor Neurochemistry/The 55th Annual Meetingof the Japanese Society for Neurochemistry
  • Place of Presentation: KobeConvention Center, Kobe, Japan
• [Presentation] Deficitsin sensorimotor gating and social behavior inbrain-specific Phgdh knockout mice (2012)
  • Author(s): Tadashi Ogo, Akihiro Watanabe, ShozoTomonaga, Yoshio Hirabayashi, Keizo Takao,Tsuyoshi Miyakawa, Shigeki Furuya
  • Organizer: The 35th Annual Meeting of the Japan NeuroscienceSociety
  • Place of Presentation: NagoyaCongress Center, Nagoya, Japan
• [Presentation] Possible link between altered geneexpression profiles and unusual sphingolipidproduction in Phgdh-deficient mouseembryonic fibroblast (2012)
  • Author(s): omoko Sayano, Kayoko Esaki, Alfred H.Merrill, Jr., Yoshio Hirabayashi, ShigekiFuruya
  • Organizer: The Gordon ResearchConference on Glycolipid & SphingolipidBiology
  • Place of Presentation: Lucca, Italy
• [Presentation] Targeted deletion of3-phosphoglycerate dehydrogenase disturbedserine and sphingolipid metabolisms of mousetissues and fibroblast cells (2012)
  • Author(s): Shigeki Furuya. Tomoko Sayano, KayokoEsaki, Alfred H. Merrill, Jr., YoshioHirabayashi
  • Organizer: The GordonResearch Conference on Glycolipid &Sphingolipid Biology
  • Place of Presentation: Lucca, Italy
• [Presentation] L-セリン生合成系による生体機能制御 (2012)
  • Author(s): 古屋 茂樹
  • Organizer: 第85回日本生化学会大会 シンポジウム1S04（L-セリン生合成系による生体機能制御）
  • Place of Presentation: 福岡市（福岡国際会議場）
  • Invited
• [Presentation] セリン欠乏による細胞毒性新奇スフィンゴ脂質の蓄積：in vivo及びin vitroにおける解析 (2012)
  • Author(s): 江崎 加代子
  • Organizer: 日本アミノ酸学会第6回学術大会
  • Place of Presentation: 松戸市（千葉大学）
• [Presentation] セリン欠乏が惹起する異常スフィンゴ脂質産生による遺伝子発現並びに細胞形態変化 (2012)
  • Author(s): 佐矢野 智子
  • Organizer: 日本アミノ酸学会第6回学術大会
  • Place of Presentation: 松戸市（千葉大学）
• [Presentation] セリン欠乏による遺伝子発現変化，形態変化と異常スフィンゴ脂質産生の機能的連関 (2012)
  • Author(s): 佐矢野 智子
  • Organizer: 第66回日本栄養・食糧学会大会
  • Place of Presentation: 仙台市（東北大学）
• [Presentation] セリン欠乏による神経毒性異常スフィンゴ脂質の蓄積：in vivo及びin vitroにおける解析 (2012)
  • Author(s): 江崎 加代子
  • Organizer: 第66回日本栄養・食糧学会大会
  • Place of Presentation: 仙台市（東北大学）
• [Presentation] Soy peptide ingestionincreases neuroactive amino acids in the adultbrain of genetically induced serine-deficientmice and wild-type mice (2011)
  • Author(s): Shigeki Furuya
  • Organizer: ICoFF2011 -International Conference on Food Factors forHealth Promotion, Symposium Session-42:Bioactive amino acids and peptides
  • Place of Presentation: Taipei International ConventionCenter, Taipei, Taiwan R.O.C.
  • Year and Date: 2011-11-22
• [Presentation] ReducedL-serine availability modulates the expressionof schizophrenia-associated genes (2011)
  • Author(s): Kayoko Esaki, Tomoko Sayano, YoshioHirabayashi, Shigeki Furuya:
  • Organizer: ICoFF2011- International Conference on Food Factors forHealth Promotion
  • Place of Presentation: Taipei International ConventionCenter, Taipei, Taiwan R.O.C.
  • Year and Date: 2011-11-22
• [Presentation] Soy peptide ingestion increases neuroactive amino acids in the adult bra in of genetically induced serine-deficient mice and wild-type mice (2011)
  • Author(s): 古屋茂樹
  • Organizer: ICoFF2011-International Conference on Food Factors for Health Promotion
  • Place of Presentation: 台北國際會議中心(台湾)
  • Year and Date: 2011-11-22
• [Presentation] 脳内L-Ser 合成不全が惹起する不安関連情動行動障害 (2011)
  • Author(s): 渡邉彰大,小河匡,高雄啓三,友永省三,平林義雄,宮川剛,古屋茂樹
  • Organizer: 日本アミノ酸学会第5回学術大会
  • Place of Presentation: 名古屋市
  • Year and Date: 2011-11-04
• [Presentation] 脳内L-Ser合成不全が惹起する不安関連情動行動障害 (2011)
  • Author(s): 渡邉彰大
  • Organizer: 2011年度日本アミノ酸学会学術大会
  • Place of Presentation: 名古屋大学(愛知県)
  • Year and Date: 2011-11-04
• [Presentation] Deficiency of Schnurri-2 confersschizophrenia-related phenotypes andinflammatory-like phenomenon in the brain (2011)
  • Author(s): Keizo Takao, Katsunori Kobayashi, HideoHagihara, Koji Ohira, Keiko Toyama, HirotakaShoji, Hironori K Nakamura, Shigeki Furuya,Tsuyoshi Takagi, Shunsuke Ishii, TsuyoshiMiyakawa
  • Organizer: 2011 The Molecular and Cellular CognitionSociety-Asia Meeting
  • Place of Presentation: Seoul, Korea
  • Year and Date: 2011-09-19
• [Presentation] セリン合成不全によるスフィンゴ脂質恒常性破綻と末梢神経障害・糖尿病関連病態 (2011)
  • Author(s): 古屋茂樹
  • Organizer: 日本アミノ酸学会第4回夏のシンポジウム
  • Place of Presentation: 新発田市
  • Year and Date: 2011-09-09
• [Presentation] セリン合成不全によるスフィンゴ脂質恒常性破綻と末梢神経障害・糖尿病関連病態 (2011)
  • Author(s): 古屋茂樹
  • Organizer: 日本アミノ酸学会第4回夏のシンポジウム
  • Place of Presentation: 月岡温泉(新潟県)(招待講演)
  • Year and Date: 2011-09-09
• [Presentation] 生後発達期におけるセリン合成不全疾患モデルマウスの脳内アミノ酸・遺伝子発現解析 (2011)
  • Author(s): 渡邉 彰大, 和田 晃. 江崎 加代子, 友永省三, 大島 敏久, 平林 義雄, 古屋 茂樹
  • Organizer: 2011 年度日本栄養・食糧学会九州・沖縄支部大会
  • Place of Presentation: 佐賀市
  • Year and Date: 2011-09-04
• [Presentation] 生後発達期におけるセリン合成不全疾患モデルマウスの脳内アミノ酸・遺伝子発現解析 (2011)
  • Author(s): 渡邉彰大
  • Organizer: 2011年度日本栄養・食糧学会九州・沖縄支部大会
  • Place of Presentation: 佐賀大学(佐賀県)
  • Year and Date: 2011-09-04
• [Presentation] グリア細胞によるL-セリン合成の生理機能を組織特異的KO マウスから探る (2010)
  • Author(s): 古屋茂樹
  • Organizer: 北海道大学・脳科学研究教育センターシンポジウム「グリアの生理と病態」
  • Place of Presentation: 札幌市
  • Year and Date: 2010-12-03
• [Presentation] マイクロアレイ解析から捉え直すセリン合成の栄養生理学的意義 (2010)
  • Author(s): 古屋茂樹
  • Organizer: 第4回日本アミノ酸学会学術集会ワークショップ
  • Place of Presentation: 日光市
  • Year and Date: 2010-09-17
• [Presentation] マイクロアレイ解析から捉え直すセリン合成の栄養生理学的意義 (2010)
  • Author(s): 古屋茂樹
  • Organizer: 第4回日本アミノ酸学会学術集会ワークショップ
  • Place of Presentation: 栃木県日光市
  • Year and Date: 2010-09-17
• [Presentation] 脳特異的Phgdh ノックアウトマウスの生後発達期における脳内アミノ酸およびモノアミン含量解析 (2010)
  • Author(s): 友永 省三, 江崎 加代子, 和田 晃, 佐矢野智子, 梁 廷訓, 大島 敏久, 古瀬 充宏, 平林 義雄, 古屋 茂樹
  • Organizer: 第33回日本神経科学大会・第53回日本神経化学会大会・第20回日本神経回路学会大会合同大会
  • Place of Presentation: 名古屋市
  • Year and Date: 2010-09-02
• [Presentation] 脳特異的Phgdhノックアウトマウスの生後発達期における脳内アミノ酸およびモノアミン含量解析 (2010)
  • Author(s): 友永省三
  • Organizer: 第26回日本神経科学大会
  • Place of Presentation: 名古屋市(名古屋国際会議場)
  • Year and Date: 2010-09-02
• [Presentation] 脳内L-セリン合成能の低下は海馬NMDA 受容体機能減弱を導く (2010)
  • Author(s): 和田 晃,梁 廷訓,佐矢野 智子,友永 省三, 田代 康介,久原 哲,三次 百合香、濱瀬 健司,吉田 一之、平林 義雄, 古屋 茂樹
  • Organizer: 第64回日本栄養・食糧学会大会
  • Place of Presentation: 徳島市
  • Year and Date: 2010-05-22
• [Presentation] 脳内L-セリン合成能の低下は海馬NMDA受容体機能減弱を導く (2010)
  • Author(s): 和田晃
  • Organizer: 第64回日本栄養・食糧学会大会
  • Place of Presentation: 徳島市(アスティ徳島)
  • Year and Date: 2010-05-22
• [Book] 先天代謝異常症候群(第2 版)ー病因・病態研究,診断・治療の進歩ー (2012)
  • Author(s): 古屋茂樹
• [Book] 先天代謝異常症候群(第2 版)ー病因・病態研究,診断・治療の進歩ー (2012)
  • Author(s): 古屋茂樹
• [Book] 先天代謝異常症候群(第2 版)ー病因・病態研究,診断・治療の進歩ー (2012)
  • Author(s): 古屋茂樹
• [Remarks]
  • URL: http://hyoka.ofc.kyushu-u.ac.jp/search/details/K002756/index.htmlhttp://www.brs.kyushu-u.ac.jp/~kinou/
• [Remarks] 九州大学研究者情報
  • URL: http://hyoka.ofc.kyushu-u.ac.jp/search/details/K002756/research.html
• [Remarks]
  • URL: http://hyoka.ofc.kyushu-u.ac.jp/search/details/K002756/research.html
• [Remarks]
  • URL: http://www.kbac.jp/furuya/
• [Remarks]
  • URL: http://www.brs.kyushu-u.ac.jp/~kinou/