A study on the molecular mechanisms of epileptic phenotype in eEF1BdeltaL knockout mice

• Project/Area Number: 15K18971
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: General physiology
• Research Institution: Kumamoto University
• Principal Investigator: KAITSUKA Taku 熊本大学, 大学院生命科学研究部(医), 助教 (00435926)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2015: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: てんかん / 恐怖条件付け / 熱ショックタンパク質 / ストレス / スプライシング

Outline of Final Research Achievements

In this study, we investigated the molecular mechanism of audiogenic seizure observed in eEF1BdeltaL knockout (KO) mouse. We found that epilepsy-related gene Cacna1a was significantly decreased in the brain of eEF1BdeltaL KO mice. Furthermore, induction of molecular chaperones was suppressed in the brain of these mice. After auditory stress, the brain atrophy was observed in KO mice. Molecular chaperones protect cells from various stresses. Our study suggests that eEF1BdeltaL might function as a safeguard against excessive response to environmental stress and gives new insight into molecular mechanism of stress-related psychiatric disorders.

Research Products

• [Int'l Joint Research] Wright State University(米国)
• [Journal Article] Erythropoietin facilitates definitive endodermal differentiation of mouse embryonic stem cells via activation of ERK signaling (2017)
  • Author(s): Kaitsuka T, Kobayashi K, Otsuka W, Kubo T, Hakim F, Wei FY, Shiraki N, Kume S and Tomizawa K
  • Journal Title: Am. J. of Physiology - Cell Physiology Volume: 312 Issue: 5 Pages: C573-C582
  • DOI: 10.1152/ajpcell.00071.2016
  • Peer Reviewed / Open Access
• [Journal Article] Mutation of the key residue for extraribosomal function of ribosomal protein S19 cause increased grooming behaviors in mice. (2016)
  • Author(s): Jun Chen, Taku Kaitsuka, Rika Fujino, Kimi Araki, Kazuhito Tomizawa, Tetsuro Yamamoto
  • Journal Title: Neuroscience letters Volume: 629 Pages: 221-226
  • DOI: 10.1016/j.neulet.2016.07.022
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] HDAC9 regulates the alternative lengthening of telomere (ALT) pathway via the formation of ALT-associated PML bodies. (2016)
  • Author(s): Mohd. Raeed Jamiruddin, Taku Kaitsuka, Farzana Hakim, Atsushi Fujimura, Fan-Yan Wei, Hisato Saitoh, Kazuhito Tomizawa
  • Journal Title: Biochemical and Biophysical Research Communications Volume: 481 Issue: 1-2 Pages: 25-30
  • DOI: 10.1016/j.bbrc.2016.11.026
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Cell-Penetrating Peptide as a Means of Directing the Differentiation of Induced-Pluripotent Stem Cells. (2015)
  • Author(s): Taku Kaitsuka, Kazuhito Tomizawa
  • Journal Title: International Journal of Molecular Sciences Volume: 16 Issue: 11 Pages: 26667-26676
  • DOI: 10.3390/ijms161125986
  • Peer Reviewed / Open Access
• [Presentation] ヒトiPS細胞の内胚葉へのヘテロ分化の要因に関する研究 (2017)
  • Author(s): 金子 瞳、貝塚 拓、富澤 一仁
  • Organizer: 第９４回 日本生理学会大会
  • Place of Presentation: 浜松アクトシティコングレスセンター（静岡県浜松市）
• [Presentation] マウス胚性幹細胞の内胚葉への分化にはエリスロポエチンによるMAPK経路の活性化が有効である (2016)
  • Author(s): 小林 幸平、貝塚 拓、Hakim Farzana、魏 范研、富澤 一仁
  • Organizer: 第９３回日本生理学会大会
  • Place of Presentation: 札幌コンベンションセンター
  • Year and Date: 2016-03-22
• [Presentation] HDAC9によるテロメア維持の組換え依存的経路の制御 (2016)
  • Author(s): Jamiruddin Mohd. Raeed、貝塚 拓、富澤 一仁
  • Organizer: 第９３回日本生理学会大会
  • Place of Presentation: 札幌コンベンションセンター
  • Year and Date: 2016-03-22
• [Presentation] The role of histone deacetylase 11 in the pluripotency of the mouse pluripotent stem cells (2016)
  • Author(s): Taku Kaitsuka, Taketo Nakashima, Kazuhito Tomizawa
  • Organizer: Cold Spring Harbor Laboratory Meeting-Mechanisms of Aging
  • Place of Presentation: コールドスプリングハーバー（米国）
  • Int'l Joint Research