Investigation of schizophrenia-like behavioral phenotypes in mice with temporal regulation of calcineurin activity

• Project/Area Number: 15K18379
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Neurochemistry/Neuropharmacology
• Research Institution: Fujita Health University
• Principal Investigator: Nakao Akito 藤田保健衛生大学, 総合医科学研究所, 助教 (30748926)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed(Fiscal Year 2017)
• Budget Amount: ¥4,290,000 (Direct Cost : ¥3,300,000、Indirect Cost : ¥990,000); Fiscal Year 2016 : ¥2,080,000 (Direct Cost : ¥1,600,000、Indirect Cost : ¥480,000); Fiscal Year 2015 : ¥2,210,000 (Direct Cost : ¥1,700,000、Indirect Cost : ¥510,000)
• Keywords: 精神疾患 / モデルマウス / 行動解析

Outline of Final Research Achievements

Forebrain-specific calcineurin knockout mice show schizophrenia-like behavioral phenotypes such as impaired working memory and increased locomotor activity. In the present study, we examined the effects of the change of calcineurin activity during the developmental stage using tetracycline-regulated gene expression system. Behavioral analyses suggest that calcineurin activity after the developmental stage may be involved in increased locomotor activity.

Research Products

• [Journal Article] Decroased brain pH as a shared endophenotype of psychiatric disorders (2018)
  • Author(s): Hagihara H, Catts VS, Katayama Y, Shoji H, Takagi T, Huang FL, Nakao A, Mori Y, Huang KP, Ishii S, Graef IA, Nakayama KI, Shannon Weickert C, *Miyakawa T
  • Journal Title: Neuropsychopharmacology Volume : 43 Pages : 459-468
  • DOI: 10.1038/npp.2017.167
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Immature morphological properties in subcellular-scale structures in the dentate gyrus of Schnurri-2 knockout mice: a model for schizophrenia and intellectual disability (2017)
  • Author(s): Nakao A et al.
  • Journal Title: Molecular Brain Volume : 10 Pages : 60-60
  • DOI: 10.1186/s13041-017-0339-2
  • Peer Reviewed / Open Access
• [Journal Article] Screening of Transient Receptor Potential Canonical Channel Activators Identifies Novel Neurotrophic Piperazine Compounds (2016)
  • Author(s): S. Sawamura, M. Hatano, Y. Takada, K. Hino, T. Kawamura, J. Tanikawa, H. Nakagawa, H. Hase, A. Nakao, M. Hirano, R. Rotrattanadumrong, S. Kiyonaka, M.X. Mori, M. Nishida, Y. Hu, R. Inoue, R. Nagata and Y. Mori
  • Journal Title: Mol Pharmacol Volume : 89(3) Pages : 348-363
  • DOI: 10.1124/mol.115.102863
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Compromised maturation of GABAergic inhibition underlies abnormal network activity in the hippocampus of epileptic Ca2+ channel mutant mice, tottering. (2015)
  • Author(s): Nakao A, Miki T, Shimono K, Oka H, Numata T, Kiyonaka S, Matsushita K, Ogura H, Niidome T, Noebels JL, Wakamori M, Imoto K, Mori Y
  • Journal Title: Pflugers Arch Volume : 467 Pages : 737-752
  • DOI: 10.1007/s00424-014-1555-6
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Comprehensive behavioral analysis of voltage-gated calcium channel beta-anchoring and -regulatory protein knockout mice (2015)
  • Author(s): Akito Nakao, Takafumi Miki, Hirotaka Shoji, Miyuki Nishi, Hiroshi Takeshima, Tsuyoshi Miyakawa, Yasuo Mori
  • Journal Title: Front Behav Neurosci Volume : 9 Pages : 141-141
  • DOI: 10.3389/fnbeh.2015.00141
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] 統合失調症モデルSchnurri-2ノックアウトマウスの歯状回顆粒細胞における三次元電子顕微鏡解析 (2017)
  • Author(s): 中尾章人、高雄啓三、大平耕司、宮崎直幸、村田和義、宮川剛
  • Organizer: 第40回日本神経科学大会
• [Presentation] Three-dimensional analysis of dendritic spines and mitochondria in dentate gyrus granule cells in Schnurri-2 knockout mice, an animal model for schizophrenia (2016)
  • Author(s): Nakao Akito, Takao Keizo, Ohira Koji, Miyazaki Naoyuki, Murata Kazuyoshi, Miyakawa Tsuyoshi
  • Organizer: 15th Annual Molecular and Cellular Cognition Society Symposium and Poster Session
  • Place of Presentation: San Diego, USA
  • Year and Date: 2016-11-10
  • Int'l Joint Research
• [Presentation] Three-dimensional analysis of morphological changes in dendritic spines and mitochondria in dentate gyrus granule cells in Schnurri-2 knockout mice, an animal model for schizophrenia (2016)
  • Author(s): Nakao Akito, Takao Keizo, Ohira Koji, Miyazaki Naoyuki, Murata Kazuyoshi, Miyakawa Tsuyoshi
  • Organizer: 46th Annual Meeting of Japanese Society of Neuropsychopharmacology
  • Place of Presentation: Seoul, Korea
  • Year and Date: 2016-07-02
• [Presentation] BARPノックアウトマウスの網羅的行動解析 (2015)
  • Author(s): 中尾 章人、昌子 浩孝、森 泰生、宮川 剛
  • Organizer: 第38回日本分子生物学会年会、第88回日本生化学会大会
  • Place of Presentation: 神戸
  • Year and Date: 2015-12-01
• [Presentation] Comprehensive behavioral analysis of voltage-gated calcium channel beta-anchoring and -regulatory protein (BARP) knockout mice (2015)
  • Author(s): Akito Nakao, Takafumi Miki, Hirotaka Shoji, Yasuo Mori, Tsuyoshi Miyakawa
  • Organizer: 14th Annual Molecular and Cellular Cognition Society Meeting
  • Place of Presentation: Chicago
  • Year and Date: 2015-10-15
  • Int'l Joint Research
• [Presentation] 新規カルシウムチャネル結合分子BARPは精神疾患様の行動異常に関与する (2015)
  • Author(s): 中尾 章人 、昌子 浩孝 、森 泰生 、宮川 剛
  • Organizer: 第38回日本神経科学大会
  • Place of Presentation: 神戸
  • Year and Date: 2015-07-30