プロテオグリカンによるシナプス伝達調節の分子メカニズム：Bral2欠損マウス解析

• Project Area: Deciphering sugar chain-based signals regulating integrative neuronal functions
• Project/Area Number: 26110713
• Research Category: Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: Okayama University
• Principal Investigator: 大橋 俊孝 岡山大学, 医歯(薬)学総合研究科, 教授 (50194262)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥8,320,000 (Direct Cost: ¥6,400,000、Indirect Cost: ¥1,920,000); Fiscal Year 2015: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2014: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
• Keywords: ペリニューロナルネット / シナプス / 台形体内側核 / ヒアルロン酸 / プロテオグリカン

Outline of Annual Research Achievements

脳幹部神経核・小脳に特異的なペリニューロナルネット(PNN)が部位特異的に障害されたBral2/Hapln4 KOマウスを用いて、PNNによる神経活動制御機構を電気生理学的手法（パッチクランプ記録法）を用いて解析した。プルキンエ細胞の軸索を電気刺激して、小脳核細胞体より抑制性シナプス後電流を記録したところ、Bral2欠損マウスではその振幅が野生型に比べて減少した。興奮性シナプス後電流に変化はなかったことから、Bral2を含むPNNが抑制性シナプス伝達に特異的に関与していることが示唆された。また、反復刺激の間に観察される短期シナプス抑圧の減少が観察されたことから、短期可塑性の変化を示された。これらの結果はプルキンエ細胞と小脳核細胞体間のシナプスにおいて、Bral2が安定したシナプス結合のために不可欠であること、短期シナプス可塑性に関与していることを示す。
PNN関連プロテオグリカン遺伝子のfloxマウスが完成し、f/+のオスメスの交配により、f/fマウスが出産され、生育上の大きな問題は観察されていない。今後同遺伝子の中枢神経系条件的KOマウス作製に供される予定である。

Research Progress Status

27年度が最終年度であるため、記入しない。

Strategy for Future Research Activity

27年度が最終年度であるため、記入しない。

Research Products

• [Int'l Joint Research] University of Cambridge(英国)
• [Int'l Joint Research] Ludwig-Maximilians-University(Germany)
• [Int'l Joint Research] University of Cambridge(英国)
• [Int'l Joint Research] Ludwig-Maximilians-University(Germany)
• [Journal Article] The hyaluronan and proteoglycan link proteins: Organizers of the brain extracellular matrix and key molecules for neuronal function and plasticity (2015)
  • Author(s): Oohashi T, Edamatsu M, Bekku Y, Carulli D
  • Journal Title: Exp Neurol Volume: 274 Pages: 134-144
  • DOI: 10.1016/j.expneurol.2015.09.010
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Modifications of perineuronal nets and remodelling of excitatory and inhibitory afferents during vestibular compensation in the adult mouse. (2015)
  • Author(s): Faralli A, Dagna F, Albera A, Bekku Y, Oohashi T, Albera R, Rossi F, Carulli D.
  • Journal Title: Brain Structure and Function. Volume: in press Issue: 6 Pages: 3193-3209
  • DOI: 10.1007/s00429-015-1095-7
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] 成熟脳のペリニューロナルECMの形成と機能について (2015)
  • Author(s): 大橋俊孝、枝松緑、別宮洋子
  • Journal Title: 生化学 Volume: 87 Pages: 393-396
  • NAID: 40020519965
  • Peer Reviewed
• [Presentation] Role of perineuronal net on synaptic function in the auditory system: a study from Hapln4/Bral2-deficient mice (2016)
  • Author(s): Toshitaka Oohashi
  • Organizer: The 3rd International Symposium on Glyco-Neuroscience
  • Place of Presentation: Awaji, Japan
  • Year and Date: 2016-01-14
  • Int'l Joint Research
• [Presentation] Analysis of perineuronal nets formation by interactions between hyaluronan and proteoglycan binding link proteins and chondroitin sulfate proteoglycans in the medial nucleus of the trapezoid body. (2016)
  • Author(s): Midori Edamatsu, Yoko Bekku and Toshitaka oohashi
  • Organizer: The 3rd International Symposium on Glyco-Neuroscience
  • Place of Presentation: Awaji, Japan
  • Year and Date: 2016-01-14
  • Int'l Joint Research
• [Presentation] ANALYSES OF THE PERINEURONAL NET FORMATION AND ITS PHYSIOLOGICAL ROLE IN THE MOUSE MEDIAL NUCLEUS OF THE TRAPEZOID BODY (2015)
  • Author(s): Toshitaka Oohashi, Midori Edamatsu, Tetsuya Hori, Mutsumi Hirata, Tomoko Yonezawa, Yoko Bekku, and Tomoyuki Takahashi
  • Organizer: 第３８回日本神経科学大会
  • Place of Presentation: 神戸国際会議場
  • Year and Date: 2015-07-28
• [Presentation] Analysis of the homeobox protein Otx2 in perineuronal nets in the auditory system (2015)
  • Author(s): Midori Edamatsu, Yoko Bekku, Toshitaka Oohashi
  • Organizer: 第３８回日本神経科学大会
  • Place of Presentation: 神戸国際会議場
  • Year and Date: 2015-07-28
• [Presentation] ANALYSES OF THE PERINEURONAL NET FORMATION AND ITS PHYSIOLOGICAL ROLE IN THE MOUSE MEDIAL NUCLEUS OF THE TRAPEZOID BODY (MNTB) (2015)
  • Author(s): Toshitaka Oohashi, Midori Edamatsu, Tetsuya Hori, Kouichi Nosaka, Takahiro Ishii, Yoko Bekku, and Tomoyuki Takahashi
  • Organizer: Hyaluronan 2015
  • Place of Presentation: Hawaii, USA
  • Year and Date: 2015-06-07
  • Int'l Joint Research
• [Presentation] The role of the extracellular matrix molecule Bral1 in the nodes of Ranvier and action potential conduction. (2015)
  • Author(s): Toshitaka Oohashi
  • Organizer: Special lecture at NICO
  • Place of Presentation: Neuroscience institute Cavalieri Ottolenghi, University of Turin, Italy
  • Invited
• [Presentation] Role of nodal protroglycan-enriched ECM on formation and maintenance of CNS node of Ranvier (2014)
  • Author(s): Toshitaka Oohashi
  • Organizer: SfG satellite Symposium, Glycans in Neuroscience
  • Place of Presentation: Hawaii, USA
  • Year and Date: 2014-11-16
  • Int'l Joint Research
• [Presentation] Analysis of the perineuronal net formation in the mouse medial nucleus of the trapezoid body (MNTB) (2014)
  • Author(s): Kouichi Nosaka, Takahiro Ishii, Midori Edamatsu, Yoko Bekku, and Toshitaka Oohashi
  • Organizer: SfG satellite Symposium, Glycans in Neuroscience
  • Place of Presentation: Hawaii, USA
  • Year and Date: 2014-11-16
  • Int'l Joint Research
• [Remarks] 岡山大学 分子医化学ホームページ
  • URL: http://www.okayama-u-mbb.jp/