Fatty acid binding protein regulates higher brain function via lipid metabolism regulation

• Project/Area Number: 26860134
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: General anatomy (including histology/embryology)
• Research Institution: Yamaguchi University
• Principal Investigator: YAMAMOTO Yui 山口大学, 医学(系)研究科(研究院), 助教 (80635087)
• Research Collaborator: OWADA Yuji 東北大学, 医学系研究科, 教授 (20292211)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2015: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 脂肪酸結合タンパク質 / GABA / GAD67 / 抑制性介在神経 / FABP / 多価不飽和脂肪酸 / 前部帯状皮質

Outline of Final Research Achievements

In this study, we examined the role of fatty asid binding protein 3 (FABP3) in the regulation of GABA synthesis and neurotransmission, mainly by using FABP3 gene ablated mice. The following results have been so far obtained: 1. In ACC of FABP3 KO mice, GAD67 promoter methylation and binding of MeCP2 and HDAC1 to GAD67 promoter were significantly decreased compared with wild-type mice. 2. To determine whether FABP3 directly regulates synaptic plasticity in the ACC, we recorded the amplitude and frequency of miniature IPSCs (mIPSCs) in ACC neurons. the mIPSC frequency was significantly increased in FABP3 KO mice compared with wild-type mice. On the other hand, the mIPSC amplitude was unchanged, suggesting that the loss of FABP3 produces alterations in inhibitory synaptic transmission. These findings suggest that DNA hypomethylation and the associated chromatin remodeling underlie the elevation of GAD67 in ACC and the abnormal behaviors and excitatory/inhibitory balance of FABP3 KO mice.

Research Products

• [Journal Article] Inhibition of fatty acid synthase decreases expression of stemness markers in glioma stem cells. (2016)
  • Author(s): Yasumoto Y., Miyazaki H., Vaidyan L.K., Kagawa Y., Ebrahimi M., Yamamoto Y., Ogata M., Katsuyama Y., Sadahiro H., Suzuki M., & Owada Y.
  • Journal Title: PLoS One Volume: 11(1) Issue: 1 Pages: 11-11
  • DOI: 10.1371/journal.pone.0147717
  • Peer Reviewed / Open Access
• [Journal Article] Astrocyte-expressed FABP7 regulates dendritic morphology and excitatory synaptic function of cortical neurons. (2016)
  • Author(s): Ebrahimi M, Yamamoto Y, Sharifi K, Kida H, Kagawa Y, Yasumoto Y, Islam A, Miyazaki H, Shimamoto C, Maekawa M, Mitsushima D, Yoshikawa T, Owada Y.
  • Journal Title: Glia Volume: 64(1) Issue: 1 Pages: 48-62
  • DOI: 10.1002/glia.22902
  • Peer Reviewed / Open Access
• [Journal Article] Fatty acid-binding protein 5 facilitates the blood-brain barrier transport of docosahexaenoic acid. (2015)
  • Author(s): Pan Y, Scanlon MJ, Owada Y, Yamamoto Y, Porter CJ, Nicolazzo PA.
  • Journal Title: Mol Pharm Volume: 12 Issue: 12 Pages: 4375-4385
  • DOI: 10.1021/acs.molpharmaceut.5b00580
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Fatty acid-binding protein 7 regulates function of caveolae in astrocytes through expression of caveolin-1. (2015)
  • Author(s): Yoshiteru Kagawa, Yuki Yasumoto, Kazem Sharifi, Majid Ebrahimi, Ariful Islam, Hirofumi Miyazaki, Yui Yamamoto, Tomoo Sawada, Hiroko Kishi, Sei Kobayashi, Motoko Maekawa, Takeo Yoshikawa, Eiichi Takaki, Akira Nakai, Hiroshi Kogo, Toyoshi Fujimoto and Yuji Owada
  • Journal Title: Glia Volume: 63 Issue: 5 Pages: 780-794
  • DOI: 10.1002/glia.22784
  • Peer Reviewed / Open Access
• [Journal Article] Proteomic differential display analysis reveals decreased expression of PEA-15 and vimentin in FABP7-deficient astrocytes. (2015)
  • Author(s): Ebrahimi, M., Sharifi, K., Islam, A., Miyazaki, H., Yasumoto, Y., Kagawa, Y., Yamamoto, Y., Kitagawa, T., Kuramitsu, Y., Nakamura, K. and Owada, Y.
  • Journal Title: J Proteom Bioinform. Volume: 8 Issue: 01 Pages: 9-14
  • DOI: 10.4172/jpb.1000347
  • Peer Reviewed / Open Access
• [Journal Article] Fatty acid binding protein 3 is involved in n-3 and n-6 PUFA transport in mouse trophoblasts. (2014)
  • Author(s): Islam, A., Kagawa, Y., Sharifi, K., Ebrahimi, M., Miyazaki, H., Yasumoto, Y., Kawamura, S., Yamamoto, Y., Sakaguti , S., Sawada, T., Tokuda, N., Sugino, N., Suzuki, R. and Owada, Y.
  • Journal Title: J Nutr Volume: 144 Issue: 10 Pages: 1509-1516
  • DOI: 10.3945/jn.114.197202
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Fatty acid binding protein 7 regulates phagocytosis and cytokine production in Kupffer cells during liver injury. (2014)
  • Author(s): Miyazaki, H., Sawada, T., Kiyohira, M., Yu, Z., Nakamura, K., Yasumoto, Y., Kagawa, Y., Ebrahimi, M., Islam, A., Sharifi, K., Kawamura, S., Kodama, T., Yamamoto, Y., Adachi, Y., Tokuda, N., Terai, S., Sakaida, I., Ishikawa, T. and Owada, Y.
  • Journal Title: Am J Pathol Volume: 184 Issue: 9 Pages: 2505-2515
  • DOI: 10.1016/j.ajpath.2014.05.015
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] 抑制性介在ニューロンにおける脂肪酸結合タンパク質ＦＡＢＰ3の機能 (2016)
  • Author(s): 山本 由似
  • Organizer: 第121回日本解剖学会総会・全国学術集会
  • Place of Presentation: ビッグパレットふくしま(福島県郡山市)
  • Year and Date: 2016-03-28
• [Presentation] 脂肪酸結合蛋白質3（FABP3）は前帯状皮質においてGAD67発現を制御する (2016)
  • Author(s): 山本 由似
  • Organizer: 第89回日本薬理学会年会
  • Place of Presentation: パシフィコ横浜(神奈川県横浜市)
  • Year and Date: 2016-03-09
• [Presentation] FABP3 遺伝子欠損マウスの認知・情動行動異常とメチオニンによる改善作用 (2015)
  • Author(s): 山本 由似
  • Organizer: 第45回日本神経精神薬理学会・第37回日本生物学的精神医学会合同年会
  • Place of Presentation: タワーホール船堀（東京都江戸川区）
  • Year and Date: 2015-09-24
• [Presentation] メチオニンはFABP3遺伝子欠損マウスにおけるGAD67の発現上昇と行動異常を改善する (2015)
  • Author(s): 山本 由似、木田 裕之、美津島 大、大和田 祐二
  • Organizer: 第120回日本解剖学会総会・全国学術集会
  • Place of Presentation: 神戸国際会議場・展示場(兵庫県神戸市）
  • Year and Date: 2015-03-21
• [Presentation] FABP3 遺伝子欠損マウスにおけるGAD67 の発現上昇と行動異常のメチオニン投与による改善作用 (2015)
  • Author(s): 山本 由似、木田 裕之、美津島 大、福永 浩司、大和田 祐二
  • Organizer: 第88回日本薬理学会年会
  • Place of Presentation: 名古屋国際会議場（愛知県名古屋市）
  • Year and Date: 2015-03-18
• [Presentation] 精神神経疾患を理解するための脂肪酸結合タンパク質（FABP）研究 (2015)
  • Author(s): 山本 由似、大和田 祐二
  • Organizer: 第30回時間学研究セミナー「生物の発生と進化の時間」
  • Place of Presentation: 山口大学（山口県山口市）
  • Year and Date: 2015-01-23
  • Invited
• [Presentation] Localization of FABP3 in the mouse cingulate cortex and its possible role in the regulation of inhibitory neurons. (2014)
  • Author(s): Yamamoto, Y., Sharifi, K., Islam, A., Ebrahimi, M., Yasumoto, Y.,Miyazaki, H., Kagawa, Y., Sawada, T., Tokuda, N., Fukunaga, K. and Owada, Y.
  • Organizer: Neuroscience 2014
  • Place of Presentation: Washington D.C.（USA)
  • Year and Date: 2014-11-17
• [Presentation] 脂肪酸結合蛋白質の脂質代謝制御による高次脳機能発現調節 (2014)
  • Author(s): 山本 由似
  • Organizer: 第36回日本生物学的精神医学会・第57回日本神経化学会大会（合同年会）、第3回生物学的精神医学会若手研究者育成プログラム
  • Place of Presentation: 奈良県新公会堂(奈良県奈良市）
  • Year and Date: 2014-09-30
• [Presentation] 脳内脂質環境の食事による変化と高次脳機能への影響 (2014)
  • Author(s): 山本 由似
  • Organizer: 第68回日本栄養・食糧学会大会
  • Place of Presentation: 酪農学園大学（北海道江別市）
  • Year and Date: 2014-06-01
• [Remarks] 山口大学大学院医学系研究科 器官解剖学分野
  • URL: http://ds.cc.yamaguchi-u.ac.jp/~org-anat/index.html
• [Remarks] 山口大学大学院医学系研究科 器官解剖学分野
  • URL: http://ds.cc.yamaguchi-u.ac.jp/~org-anat/