Study on the molecular basis underlying the disorder and recovery of sociality in inbred mouse strains

• Project/Area Number: 15K14356
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Neurochemistry/Neuropharmacology
• Research Institution: Tokyo University of Science
• Principal Investigator: FURUICHI TEIICHI 東京理科大学, 理工学部応用生物科学科, 教授 (50219094)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 自閉症スペクトラム障害 / トランスクリプトーム / CAPS2 / 社会行動 / 分子神経科学 / BTBRマウス

Outline of Final Research Achievements

In this study, we performed comparative transcriptomic analysis of the cerebral cortex and basal ganglia between C57BL/6 and BTBR mice that show high and low sociality, respectively. The results showed the presence of some interesting genes with increased or decreased expression levels in BTBR brain compared to C57BL/6 brain. We also identified increased expression of exocytosis-related genes Stx5a and Syt6 and decreased expression of developmental disorder-related genes Mecp2 and Oxtr in the cerebellum of CAPS2 KO mice compared to the wild type mice.

Research Products

• [Journal Article] The brain-specific RasGEF very-KIND is required for normal dendritic growth in cerebellar granule cells and proper motor coordination (2017)
  • Author(s): Hayashi K, Furuya A, Sakamaki Y, Akagi T, Shinoda Y, Sadakata T, Hashikawa T, Shimizu K, Minami H, Sano Y, Nakayama M, and Furuichi T.
  • Journal Title: PLoS ONE Volume: 12 Issue: 3 Pages: e0173175-e0173175
  • DOI: 10.1371/journal.pone.0173175
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Analysis of gene expression in Ca2+-dependent activator protein for secretion 2 (Cadps2) knockout cerebellum using GeneChip and KEGG pathways (2016)
  • Author(s): Sadakata T, Shinoda Y, Ishizaki Y, Furuichi T.
  • Journal Title: Neuroscience Letters Volume: 639 Pages: 88-93
  • DOI: 10.1016/j.neulet.2016.12.068
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] CAPS1 stabilizes the state of readily releasable synaptic vesicles to fusion competence at CA3-CA1 synapses in adult hippocampus (2016)
  • Author(s): 6.Shinoda Y, Ishii C, Fukazawa Y, Sadakata T, Ishii Y, Sano Y, Iwasato T, Itohara S, Furuichi T
  • Journal Title: Scientific Reports Volume: 6 Issue: 1 Pages: 31540-31540
  • DOI: 10.1038/srep31540
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Interaction of Ca2+-dependent activator protein for secretion 1 (CAPS1) with septin family proteins in mouse brain (2016)
  • Author(s): Hosono M, Shinoda Y, Hirano T, Ishizaki Y, Furuichi T and Sadakata T
  • Journal Title: Neurosci. Lett. Volume: 617 Pages: 232-235
  • DOI: 10.1016/j.neulet.2016.02.035
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Mammalian-specific central myelin protein Opalin is redundant for normal myelination: structural and behavioral assessments (2016)
  • Author(s): Yoshikawa, F., Sato, Y., Tohyama, K., Akagi, T., Furuse, T., Sadakata, T., Tanaka, M., Shinoda, Y., Hashikawa, T., Itohara, S., Sano, Y., Ghandour, SM., Wakana, S., and Furuichi, T.
  • Journal Title: PLoS ONE Volume: 11 Issue: 11 Pages: e0166732-e0166732
  • DOI: 10.1371/journal.pone.0166732
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Galacto-N-biose is neuroprotective against glutamate-induced excitotoxicity in vitro. (2016)
  • Author(s): Shinoda, Y., Nakajima, Y., Iguchi, H., Tatsumi, S., Kitaoka, M., Nakajima, M., Takahashi, T., Fujiwara, M., and Furuichi, T.
  • Journal Title: Eur. J. Pharmacol. Volume: 791 Pages: 711-717
  • DOI: 10.1016/j.ejphar.2016.10.010
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Low doses of the mycotoxin citrinin protect cortical neurons against glutamate-induced excitotoxicity (2016)
  • Author(s): Nakajima Y, Iguchi H, Kamisuki S, Sugawara F, Furuichi T and Shinoda Y
  • Journal Title: The Journal of Toxicological Sciences Volume: 41 Issue: 2 Pages: 311-319
  • DOI: 10.2131/jts.41.311
  • NAID: 130005132670
  • ISSN: 0388-1350, 1880-3989
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Lack of stress responses to long-term effects of corticosterone in Caps2 knockout mice. (2015)
  • Author(s): Yuriko Mishima, Yo Shinoda, Tetsushi Sadakata, Masami Kojima, Shigeharu Wakana, Teiichi Furuichi.
  • Journal Title: Scientific Reports Volume: 5 Issue: 1 Pages: 1-6
  • DOI: 10.1038/srep08932
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] 分泌小胞関連タンパク質CAPS遺伝子改変マウスが示すシナプスの形態と生理の異常および社会行動障害について (2017)
  • Author(s): 古市貞一
  • Organizer: 第122回日本解剖学会総会・全国学術集会
  • Place of Presentation: 長崎県長崎市・長崎大学坂本キャンパス
  • Year and Date: 2017-03-28
  • Invited
• [Presentation] A deficiency of Ca2+-dependent activator protein for secretion 1 affects hippocampal long-term potentiation (2016)
  • Author(s): Y. Ishii, C. Ishii, Y. Shinoda, Y. Sano, T. Furuichi
  • Organizer: Society for Neuroscience
  • Place of Presentation: San Diego, CA, U.S.A.
  • Year and Date: 2016-11-12
  • Int'l Joint Research
• [Presentation] A rubber tail task in Ca2+-dependent activator protein for secretion (CAPS2) knockout mice (2016)
  • Author(s): M. Wada, M. Ide, T. Atsumi, K. Yagishita, M., Katakai, Y., Shinoda, T. Furuichi, K.,Kansaku
  • Organizer: Society for Neuroscience
  • Place of Presentation: San Diego, CA, U.S.A.
  • Year and Date: 2016-11-12
  • Int'l Joint Research
• [Presentation] Enhancing Brain Transcriptome Database by Neural Gene Ontology (2016)
  • Author(s): T. Furuichi
  • Organizer: 第39回日本神経科学大会
  • Place of Presentation: 神奈川県横浜市・パシフィコ横浜
  • Year and Date: 2016-07-20
  • Invited
• [Presentation] Databasing brain gene expression information (2016)
  • Author(s): T. Furuichi
  • Organizer: 4th INCF Japan Node International Workshop Advances in Neuroinformatics 2016 and 14th INCF Nodes Workshop
  • Place of Presentation: RIKEN Suzuki Umetaro Hall, Wako, Japan
  • Year and Date: 2016-05-28
  • Int'l Joint Research / Invited
• [Presentation] Brain Transcriptome Database (BrainTx) (2016)
  • Author(s): A. Sato, N. Munemura, Y. Sano, Y. Shinoda, T. Sadakata, N. Morita, M. Yuzaki, T. Inoue, M. Hashimoto, H. Ohwada, H. Nishibe, Y. Yamaguchi, T. Furuichi
  • Organizer: 4th INCF Japan Node International Workshop Advances in Neuroinformatics 2016 and 14th INCF Nodes Workshop
  • Place of Presentation: RIKEN Suzuki Umemotaro Hall, Wako, Japan
  • Year and Date: 2016-05-28
  • Int'l Joint Research
• [Presentation] Parallelization of the registration method for ISH images into the 3D standard brain atlas (2016)
  • Author(s): D. Miyammoto, H. Ikeno, Y. Okamura-Oho, Y. Okamura, N. Munemura, A. Sato, Y. Yamaguchi, R. Kanzaki, T. Furuichi
  • Organizer: 4th INCF Japan Node International Workshop Advances in Neuroinformatics 2016 and 14th INCF Node Workshop
  • Place of Presentation: RIKEN Suzuki Umemotaro Hall, Wako, Japan
  • Year and Date: 2016-05-28
  • Int'l Joint Research
• [Presentation] Brain development transcriptome database and developmental disorder. (2015)
  • Author(s): Teiichi Furuichi
  • Organizer: 15th China-Japan-Korea Joint Workshop on Neurobiology and Neuroinformatics
  • Place of Presentation: Haeundae Centum Hotel (Busan, Korea)
  • Year and Date: 2015-12-21
  • Int'l Joint Research / Invited
• [Presentation] The molecular mechanisms of brain development and disorders. (2015)
  • Author(s): Teiichi Furuichi, Yo Shinoda, Tetsushi Sadakata
  • Organizer: Neuroinformatics 2015
  • Place of Presentation: Pullman Cairns International (Cairns, Australia)
  • Year and Date: 2015-08-20
  • Int'l Joint Research / Invited
• [Presentation] Reduced axonal localization of a CAPS2 splicing variant impairs axonal release of BDNF and causes autistic-like behavior in mice. (2015)
  • Author(s): Sadakata T., Furuichi T.
  • Organizer: The 38th Annual Meeting of the Japan Neuroscience Society
  • Place of Presentation: 神戸コンベンションセンター（兵庫県神戸市）
  • Year and Date: 2015-07-28
• [Presentation] Possible involvement of CAPS2 in environmental enrichment-dependent adult neurogenesis in mouse hippocampus. (2015)
  • Author(s): Yagishita K., Shinoda Y., Senba R., Furuichi T.
  • Organizer: The 38th Annual Meeting of the Japan Neuroscience Society
  • Place of Presentation: 神戸コンベンションセンター（兵庫県神戸市）
  • Year and Date: 2015-07-28
• [Presentation] Animal models of autism spectrum disorders: CAPS2 is critical for proper brain development and social behavior. (2015)
  • Author(s): Teiichi Furuichi, Yo Shinoda, Tetsushi Sadakata
  • Organizer: International Symposium of the Center for Animal Disease Models.
  • Place of Presentation: Gakushikaikan, (Chiyoda-ku, Tokyo)
  • Year and Date: 2015-07-21
  • Int'l Joint Research / Invited
• [Remarks] Lab of Molecular Neuroscience -Furuichi Lab
  • URL: http://www.lmn.bs.noda.tus.ac.jp/
• [Remarks] 東京理科大学理工学部応用生物科学科古市貞一
  • URL: http://www.tus.ac.jp/fac_grad/p/index.php?64da