Studies on mental disorder using patient-specific iPS cells

• Project/Area Number: 26860055
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Pharmacology in pharmacy
• Research Institution: Osaka University
• Principal Investigator: Nagayasu Kazuki 大阪大学, 薬学研究科, 助教 (00717902)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2014: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: 幹細胞 / ウイルスベクター / 精神疾患 / iPS細胞 / 神経幹細胞 / 神経細胞

Outline of Final Research Achievements

It has been suggested that patient-specific iPS cells are promising resource to reveal the mechanisms of mental disorders. Lines of evidences indicate that abnormalities during neural development play a critical role in the development of mental disorders such as autism and schizophrenia. However, little is known about molecular mechanisms of the development of mental disorders. To unveil it, here we improved differentiation method for neural induction from human iPS cells and investigated possible mechanisms of the development of mental disorders.

Research Products

• [Journal Article] Role of the 5-HT4 receptor in chronic fluoxetine treatment-induced neurogenic activity and granule cell dematuration in the dentate gyrus (2015)
  • Author(s): Yuki Imoto, Toshihiko Kira, Mamiko Sukeno, Naoya Nishitani, Kazuki Nagayasu, Takayuki Nakagawa, Shuji Kaneko, Katsunori Kobayashi, Eri Segi-Nishida
  • Journal Title: Molecular Brain Volume: 8 Issue: 1 Pages: 29-29
  • DOI: 10.1186/s13041-015-0120-3
  • NAID: 120005758229
  • Peer Reviewed / Open Access
• [Journal Article] p13 overexpression in pancreatic b-cells ameliorates type 2 diabetes in high-fat-fed mice (2015)
  • Author(s): Higashi, S. et al.
  • Journal Title: Biochemical and Biophysical Research Communications Volume: 461 Issue: 4 Pages: 612-617
  • DOI: 10.1016/j.bbrc.2015.04.074
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Olanzapine augments the effect of selective serotonin reuptake inhibitors by suppressing GABAergic inhibition via antagonism of 5-HT₆ receptors in the dorsal raphe nucleus. (2015)
  • Author(s): Asaoka N*, Nagayasu K*, Nishitani N, Yamashiro M, Shirakawa H, Nakagawa T, Kaneko S.
  • Journal Title: Neuropharmacology. Volume: 95 Pages: 261-268
  • DOI: 10.1016/j.neuropharm.2015.03.032
  • Peer Reviewed
• [Journal Article] Whole-exome sequencing and neurite outgrowth analysis in autism spectrum disorder. (2015)
  • Author(s): Hashimoto R, Nakazawa T, Tsurusaki Y, Yasuda Y, Nagayasu K, Matsumura K, Kawashima H, Yamamori H, Fujimoto M, Ohi K, Umeda-Yano S, Fukunaga M, Fujino H, Kasai A, Hayata-Takano A, Shintani N, Takeda M, Matsumoto N, Hashimoto H.
  • Journal Title: Journal of Human Genetics Volume: 61 Issue: 3 Pages: 199-206
  • DOI: 10.1038/jhg.2015.141
  • Peer Reviewed / Open Access
• [Journal Article] Identification of the role of BMP and TGF-β signaling in the trajectory of serotonergic differentiation in a rapid assay in mouse embryonic stem cells in vitro. (2015)
  • Author(s): Yamasaki A, Kasai A, Toi A, Kurita M, Kimoto S, Hayata-Takano A, Nakazawa T, Nagayasu K, Shintani N, Hashimoto R, Ito A, Meltzer HY, Ago Y, Waschek JA, Onaka Y, matsuda T, Baba A, Hashimoto H.
  • Journal Title: Journal of Neurochemistry, Volume: 132(4) Issue: 4 Pages: 418-428
  • DOI: 10.1111/jnc.12999
  • Peer Reviewed / Open Access
• [Journal Article] CRTH2, a prostaglandin D2 receptor, mediates depression-related behavior in mice (2015)
  • Author(s): Yusuke Onaka, Norihito Shintani, Takanobu Nakazawa, Ryota Haba, Yukio Ago, Hyper Wang, Takuya Kanoh, Atsuko Hayata-Takano, Hiroyuki Hirai, Kin-ya Nagata, Masataka Nakamura, Ryota Hashimoto, Toshio Matsuda, James A. Waschek, Atsushi Kasai, Kazuki Nagayasu, Akemichi Baba, Hitoshi Hashimoto
  • Journal Title: Behavioural Brain Research Volume: 284 Pages: 131-137
  • DOI: 10.1016/j.bbr.2015.02.013
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Simultaneous neuron- and astrocyte-specific fluorescent marking. (2015)
  • Author(s): Schulze W, Hayata-Takano A, Kamo T, Nakazawa T, Nagayasu K, Kasai A, Seiriki K, Shintani N, Ago Y, Farfan C, Hashimoto R, Baba A, Hashimoto H.
  • Journal Title: Biochemical and Biophysical Research Communications Volume: 459 Issue: 1 Pages: 81-86
  • DOI: 10.1016/j.bbrc.2015.02.073
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Inhibition of histone deacetylases enhances the function of serotoninergic neurons in organotypic raphe slice cultures. (2015)
  • Author(s): Asaoka N, Nagayasu K, Nishitani N, Yamashiro M, Shirakawa H, Nakagawa T, Kaneko S.
  • Journal Title: Neurosci Lett. Volume: 593 Pages: 72-77
  • DOI: 10.1016/j.neulet.2015.03.028
  • NAID: 120005657906
  • Peer Reviewed
• [Journal Article] PACAP Enhances Axon Outgrowth in Cultured Hippocampal Neurons to a Comparable Extent as BDNF. (2015)
  • Author(s): Ogata K, Shintani N, Hayata-takano A, Kamo T, Higashi S, Seiriki K, Momosaki H, Vaudy D, Vaudy H, Galas L, Kasai A, Nagayasu K, Nakazawa T, Hashimoto R, Ago Y, Matsuda T, Baba A, Hashimoto H.
  • Journal Title: PLoS One Volume: 10 Issue: 3 Pages: e0120526-e0120526
  • DOI: 10.1371/journal.pone.0120526
  • Peer Reviewed / Open Access
• [Journal Article] A mouse model of human primitive neuroectodermal tumors resulting from microenvironmentally-driven malignant transformation of orthotopically transplanted radial glial cells. (2015)
  • Author(s): Malchenko S, Sredni ST, Hashimoto H, Kasai A, Nagayasu K, Xie J, Margaryan NV, Seiriki K, Lulla RR, Seftor RE, Pachman LM, Meltzer HY, Hendrix MJ, Soares MB
  • Journal Title: PLoS One Volume: 10 Issue: 3 Pages: e0121707-e0121707
  • DOI: 10.1371/journal.pone.0121707
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Atomoxetine reverses locomotor hyperactivity, impaired novel object recognition, and prepulse inhibition impairment in mice lacking pituitary adenylate cyclase-activating polypeptide (PACAP). (2015)
  • Author(s): hibasaki Y, Hayata-Takano A, Hazama K, Nakazawa T, Shintani N, Kasai A, Nagayasu K, Hashimoto R, Tanida M, Katayama T, Matsuzaki S, Yamada K, Taniike M, Onaka Y, Ago Y, Waschek JA, Köves K, Reglődi D, Tamas A, Matsuda T, Baba A, Hashimoto H.
  • Journal Title: Neuroscience Volume: 297 Pages: 95-104
  • DOI: 10.1016/j.neuroscience.2015.03.062
  • Peer Reviewed
• [Journal Article] Control of intermale aggression by the medial prefrontal cortex activation in the mouse (2014)
  • Author(s): Takahashi A, Nagayasu K, Nishitani N, Kaneko S, Koide T
  • Journal Title: PLoS ONE Volume: 9(4) Issue: 4 Pages: 94657-94657
  • DOI: 10.1371/journal.pone.0094657
  • Peer Reviewed / Open Access
• [Journal Article] Raphe AMPA receptors and nicotinic acetylcholine receptors mediate ketamine-induced serotonin release in the rat prefrontal cortex. (2014)
  • Author(s): Nishitani N. et al.
  • Journal Title: The International Journal of Neuropsychopharmacology Volume: in press Issue: 08 Pages: 1321-1326
  • DOI: 10.1017/s1461145714000649
  • Peer Reviewed
• [Journal Article] Behavioral characterization of mice overexpressing human dysbindin-1 (2014)
  • Author(s): Shintani N, Onaka Y, Hashimoto R, Takamura H, Nagata T, Umeda-Yano S, Mouri A, Mamiya T, Haba R, Matsuzaki S, Katayama T, Yamamori H, Nakazawa T, Nagayasu K, Ago Y, Yagasaki Y, Nabeshima T, Takeda M, Hashimoto H
  • Journal Title: Molecular Brain Volume: 7(1) Issue: 1 Pages: 74-74
  • DOI: 10.1186/s13041-014-0074-x
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] Studies on the molecular mechanism of clozapine action with iPSC technology (2016)
  • Author(s): M. Fujiwara, M. Kikuchi, K. Nagayasu, T. nakazawa, H. Yamamori, A. Kasai, A. Hayata-Takano, N. Shintani, M. Fujimoto, Y. Yasuda, M. Ishikawa, W. Akamatsu, H. Okano, A. Nakaya, H. Hashimoto, R. Hashimoto
  • Organizer: 第89回日本薬理学会年会
  • Place of Presentation: 神奈川県
  • Year and Date: 2016-03-11
• [Presentation] 背側縫線核セロトニン神経による情動調節機構―ウイルスベクターを用いて― (2016)
  • Author(s): 永安 一樹、金子 周司
  • Organizer: 第89回日本薬理学会年会
  • Place of Presentation: 神奈川県
  • Year and Date: 2016-03-11
• [Presentation] アデノ・アデノ随伴・レンチウイルスベクターの作製と応用 (2016)
  • Author(s): 永安 一樹
  • Organizer: 第89回日本薬理学会年会
  • Place of Presentation: 神奈川県
  • Year and Date: 2016-03-10
• [Presentation] セロトニン神経機能に関わる遺伝子発現に対するmiRNAの作用 (2015)
  • Author(s): 大住康晃, 永安一樹, 笠井淳司, 木本早紀, 尾中勇祐, 早田敦子, 中澤敬信, 新谷紀人, 橋本 均
  • Organizer: 第128回日本薬理学会近畿部会
  • Place of Presentation: 大阪府
  • Year and Date: 2015-11-20
• [Presentation] Practical optimization of.in situ hybridization procedure for the detection of microRNAs and mRNA expression in brain tissues (2015)
  • Author(s): Kasai A, Kakihara S, Okada R, Hazama K, Nakazawa T, Nagayasu K, Hayata-Takano A, Shintani N, Hashimoto H
  • Organizer: Neuroscience 2015
  • Place of Presentation: シカゴ
  • Year and Date: 2015-10-17
  • Int'l Joint Research
• [Presentation] miRNAを介したPACAPによる樹状突起スパイン形成機構 (2015)
  • Author(s): 加茂俊彦、早田敦子、勢力薫、尾形勝弥、中澤敬信, 永安一樹, 笠井淳司, 新谷紀人, 橋本均
  • Organizer: 第45回日本神経精神薬理学会・第37回日本生物学的精神医学会合同年会
  • Place of Presentation: 東京都
  • Year and Date: 2015-09-24
• [Presentation] A screening method for functional analysis of autism-associated genes (2015)
  • Author(s): Matsumura K., Hashimoto R., Nakazawa T., Tsurusaki Y., Yasuda Y., Nagayasu K., Kawashima H., Yamamori H., Fujimoto M, Ohi K., Satomi U., Fukunaga M., Fujino H., Kasai A., Hayata A., Shintani N., Takeda M., Matsumoto N., Hashimoto H.
  • Organizer: 第38回日本神経科学大会
  • Place of Presentation: 兵庫県
  • Year and Date: 2015-07-28
• [Presentation] がん治療後の脳機能障害の解明に有用な動物モデルの作製 (2015)
  • Author(s): 尾中 勇祐、木野村 元彦、新谷 紀人、平井 博之、永田 欽也、中村 正孝、長谷部 茂、永安 一樹、吾郷 由希夫、笠井 淳司、早田 敦子、中澤 敬信、田熊 一敞、松田 敏夫、馬場 明道、橋本 均
  • Organizer: 第127回日本薬理学会近畿部会
  • Place of Presentation: 岐阜県
  • Year and Date: 2015-06-26
• [Presentation] 自閉スペクトラム症関連候補遺伝子のハイスループット機能評価系による解析 (2014)
  • Author(s): 永安一樹、松村憲佑、中澤敬信、安田由華、山森英長、梅田知美、大井一高、橋本亮太、武田雅俊、橋本均
  • Organizer: 2014年度包括脳ネットワーク冬のシンポジウム
  • Place of Presentation: 東京
  • Year and Date: 2014-12-12 – 2014-12-13
• [Presentation] 光遺伝学的手法を用いた背側縫線核セロトニン神経特異的制御による行動学的変化 (2014)
  • Author(s): 西谷直也、永安一樹、浅岡希美、山城茉弓、白川久志、中川貴之、金子周司
  • Organizer: 2014年度包括脳ネットワーク冬のシンポジウム
  • Place of Presentation: 東京
  • Year and Date: 2014-12-12 – 2014-12-13
• [Presentation] iPS細胞関連技術を用いた統合失調症研究 (2014)
  • Author(s): 中澤敬信、橋本亮太、永安一樹、安田由華、山森英長、梅田知美、藤本美智子、大井一高、石川充、赤松和土、岡野栄之、武田雅俊、橋本均
  • Organizer: 第24回 日本臨床精神神経薬理学会 第44回日本神経精神薬理学会 合同年会
  • Place of Presentation: 名古屋
  • Year and Date: 2014-11-20 – 2014-11-22
• [Presentation] 自閉症の疾患特異的候補遺伝子の機能的スクリーニング系の確立 (2014)
  • Author(s): 松村憲佑、永安一樹、中澤敬信、安田由華、山森英長、梅田知美、大井一高、橋本亮太、武田雅俊、橋本均
  • Organizer: 第24回 日本臨床精神神経薬理学会 第44回日本神経精神薬理学会 合同年会
  • Place of Presentation: 名古屋
  • Year and Date: 2014-11-20 – 2014-11-22
• [Presentation] ヒストン脱アセチル化酵素阻害薬の持続処置が縫線核セロトニン神経に与える影響 (2014)
  • Author(s): 浅岡希美、永安一樹、西谷直也、山城茉弓、白川久志、中川貴之、金子周司
  • Organizer: 第24回 日本臨床精神神経薬理学会 第44回日本神経精神薬理学会 合同年会
  • Place of Presentation: 名古屋
  • Year and Date: 2014-11-20 – 2014-11-22
• [Presentation] ケタミンは縫線核AMPA受容体およびニコチン性アセチルコリン受容体を介して前頭前皮質5-HT遊離を引き起こす (2014)
  • Author(s): 西谷直也、永安一樹、浅岡希美、山城茉弓、白川久志、中川貴之、金子周司
  • Organizer: 第24回 日本臨床精神神経薬理学会 第44回日本神経精神薬理学会 合同年会
  • Place of Presentation: 名古屋
  • Year and Date: 2014-11-20 – 2014-11-22
• [Presentation] Lentiviral vector system for potent gene expression in serotonergic neurons of rats and mice (2014)
  • Author(s): K. NAGAYASU, N. NISHITANI, N. ASAOKA, M. YAMASHIRO, H. SHIRAKAWA, T. NAKAGAWA, S. KASPAROV, S. KANEKO
  • Organizer: Neuroscience 2014
  • Place of Presentation: Washington, DC, USA
  • Year and Date: 2014-11-15 – 2014-11-19
• [Presentation] 神経ペプチドPACAPによる精神機能調節：創薬への展望 (2014)
  • Author(s): 橋本均、新谷紀人、早田敦子、笠井淳司、永安一樹、中澤敬信
  • Organizer: 第36回日本生物学的精神医学会 第57回日本神経化学会大会 合同年会
  • Place of Presentation: 奈良
  • Year and Date: 2014-09-29 – 2014-10-01
• [Presentation] 精神・神経疾患モデル動物の病態解析のための三次元全脳形態計測法の構築 (2014)
  • Author(s): 勢力薫、笠井淳司、丹生光咲、早田敦子、永安一樹、中澤敬信、新谷紀人、橋本岳、橋本均
  • Organizer: 第36回日本生物学的精神医学会 第57回日本神経化学会大会 合同年会
  • Place of Presentation: 奈良
  • Year and Date: 2014-09-29 – 2014-10-01
• [Presentation] コルチコステロン誘発性うつ病モデルを用いたプロスタノイド受容体DP2を介する情動制御機構の解析 (2014)
  • Author(s): 尾中勇祐、新谷紀人、木野村元彦、平井博之、長田欽也、中村正孝、早田敦子、笠井淳司、永安一樹、中澤敬信、馬場明道、橋本均
  • Organizer: 生体機能と創薬シンポジウム2014
  • Place of Presentation: 大阪
  • Year and Date: 2014-08-28 – 2014-08-29
• [Presentation] 脳内miRNA発現の高感度検出に向けたin situ hybridization法の最適化：炎症により発現変化する脳内miRNAの同定 (2014)
  • Author(s): 柿原素楽, 笠井淳司, 岡田遼, 狭間啓佑, 中澤敬信, 永安一樹, 早田敦子, 新谷紀人, 橋本均
  • Organizer: 生体機能と創薬シンポジウム2014
  • Place of Presentation: 大阪
  • Year and Date: 2014-08-28 – 2014-08-29
• [Presentation] オランザピンの縫線核セロトニン神経に対する作用とSSRI作用増強機構 (2014)
  • Author(s): 浅岡希美、永安一樹、西谷直也、山城茉弓、白川久志、中川貴之、金子周司
  • Organizer: 第125回日本薬理学会近畿部会
  • Place of Presentation: 岡山
  • Year and Date: 2014-06-20