Grid2 dependent regulation of BDNF

• Project/Area Number: 25670155
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: General medical chemistry
• Research Institution: 独立行政法人医薬基盤研究所
• Principal Investigator: TAKEMORI Hiroshi 独立行政法人医薬基盤研究所, 創薬基盤研究部, プロジェクトリーダー (90273672)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2013: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: Grid2 / BDNF / 運動記憶 / 遺伝学 / マイクロサテライト解析 / GRID2 / メマンチン / NMDA / AMPA / めまい

Outline of Final Research Achievements

We identified a mouse strain with a naturally occurring mutation and an ataxic phenotype that presents with severe leg cramps. To investigate the phenotypes of these mutant mice, we screened several phenotype-modulating drugs and found that memantine (10 mg/kg) disrupted the sense of balance in the mutants. Moreover, the mutant mice showed an attenuated optokinetic response (OKR) and impaired OKR learning, which was also observed in wild-type mice treated with memantine. Microsatellite analyses indicated that the Grid2 gene-deletion is responsible for these phenotypes. Patch-clamp analysis showed a relatively small change in NMDA-dependent current in cultured granule cells from Grid2 gene-deleted mice, suggesting that GRID2 is important for correct NMDA receptor function.In addition, Grid2 mutant mice expressed abnormal BDNF protein, suggesting tat Grid2 mutant mice is helpful to analyze NMDA-R related memory.

Research Products

• [Journal Article] SIK3 deficiency exacerbates LPS-induced endotoxin shock accompanied by increased levels of proinflammatory molecules in mice. (2015)
  • Author(s): Sanosaka M, Fujimoto M, Ohkawara T, Nagatake T, Itoh Y, Kagawa M, Kumagai A, Fuchino H, Kunisawa J, Naka T, Takemori H
  • Journal Title: Immunology Volume: 144 Issue: 2 Pages: 268-278
  • DOI: 10.1111/imm.12445
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Altered Actions of Memantine and NMDA-Induced Currents in a New Grid2-Deleted Mouse Line. (2014)
  • Author(s): Ayako Kumagai, Akira Fujita, Tomoki Yokoyama, Yuki Nonobe, Yasuhiro Hasaba, Tsutomu Sasaki, Yumi Itoh, Minako Koura, Osamu Suzuki, Shigeki Adachi, Haruko Ryo, Arihiro Kohara, Lokesh P. Tripathi, Masato Sanosaka, Toshiki Fukushima, Taisei Nomura, Hiroshi Takemori, et al.
  • Journal Title: Genes Volume: 5 Issue: 4 Pages: 1095-1114
  • DOI: 10.3390/genes5041095
  • Peer Reviewed / Open Access
• [Journal Article] Lack of SIK2 prevents the development of cardiac hypertrophy in response to chronic high-salt intake (2014)
  • Author(s): Popov S.*, Takemori H.*, Tokudome T., Mao Y., Otani K., Mochizuki N., Pires N., Pinho M.J., Franco-Cereceda A., Torielli L., Ferrandi M., Hamsten A., Eriksson P., Bertorello A.M., Brion L
  • Journal Title: PLos ONE Volume: 9
  • Peer Reviewed
• [Journal Article] Induction of melanogenesis by 4'-O-methylated flavonoids in B16F10 melanoma cells. (2013)
  • Author(s): Horibe I., Satoh Y., Shiota Y., Kumagai A., Horike N., Takemori H., Uesato S., Sugie S., Obata K., Kawahara H., Nagaoka Y
  • Journal Title: J Nat Med Volume: 67 Pages: 705-710
  • Peer Reviewed
• [Presentation] GRID2はメマンチンの作用機序における新しい調節因子である (2014)
  • Author(s): 熊谷彩子、伊東祐美、賀川舞、松田潤一郎、佐々木勉、田端俊英、竹森 洋
  • Organizer: 第51回日本臨床分子医学会
  • Place of Presentation: 東京
  • Year and Date: 2014-04-11
• [Presentation] ワラビPterosinのdb/dbマウスにおける血糖値低下作 (2013)
  • Author(s): 伊東祐美、佐野坂真人、熊谷彩子、竹森 洋、渕野裕之、土居純子、太田美穂
  • Organizer: 第67回日本栄養・食糧学会
  • Place of Presentation: 名古屋
• [Patent(Industrial Property Rights)] カスパーゼ1活性化阻害剤、抗炎症剤、鎮痒剤、及びカスパーゼ１活性化阻害剤の評価方法 (2013)
  • Inventor(s): 竹森 洋、佐野坂真人、伊東祐美、渕野裕之、川原信夫
  • Industrial Property Rights Holder: 独立行政法人医薬基盤研究所、株式会社桃谷順天館
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2013-094995
  • Filing Date: 2013-04-30