Role of polyunsaturated fatty acids in the development of schizophrenia

• Project/Area Number: 21791156
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Psychiatric science
• Research Institution: The Institute of Physical and Chemical Research
• Principal Investigator: MAEKAWA Motoko The Institute of Physical and Chemical Research, 分子精神科学研究チーム, 研究員 (50435731)
• Project Period (FY): 2009 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2010: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2009: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 統合失調症 / 多価不飽和脂肪酸 / オリゴデンドロサイト / GABA / 神経発達 / 環境因子 / ARMS / 不飽和脂肪酸 / Fabp7 / Fabp5 / プレパルス抑制(PPI) / Pax6変異ヘテロラット / 神経新生 / 発達

Research Abstract

In mice fed polyunsaturated fatty acids (PUFAs)-deficient diet during the brain developmental stage, we observed broad downregulation of genes related to oligodendrocyte and GABAergic systems, which is a current theory of functional psychoses. Moreover, we revealed that 1) mice raised with PUFAs-deficient diet showed poor volition detected by Y maze test, 2) neuronal activity of such mice was altered, which was examined by Mn-enhanced MRI. These results provide innovative clues for the pathophysiology of mental disorders, demonstrating an important role of PUFAs during neurodevelopement.

Research Products

• [Journal Article] Association study of Nogo-related genes with schizophrenia in a Japanese case-control sample. (2011)
  • Author(s): Jitoku D, Hattori E, Iwayama Y, Yamada K, Toyota T, Kikuchi M, Maekawa M, Nishikawa T, Yoshikawa T.
  • Journal Title: Am J Med Genet B Neuropsychiatr Genet.[Epub ahead of print]
  • Peer Reviewed
• [Journal Article] Role of polyunsaturated fatty acids and fatty acid binding protein in the pathogenesis of schizophrenia. (2011)
  • Author(s): Maekawa M, Owada Y, Yoshikawa T.
  • Journal Title: Curr Pharm Des. 17(2) Pages: 168-175
  • Peer Reviewed
• [Journal Article] Evaluation of Pax6 mutant rat as a model for autism. (2010)
  • Author(s): Umeda T, Takashima N, Nakagawa R, Maekawa M, Ikegami S, Yoshikawa T, Kobayashi K, Okanoya K, Inokuchi K, Osumi N.
  • Journal Title: PLoS One. 5(12)
  • Peer Reviewed
• [Journal Article] Analysis of strain-dependent prepulse inhibition points to a role for Shmt1 (SHMT1) in mice and in schizophrenia (2010)
  • Author(s): Maekawa M, Ohnishi T, Hashimoto K, Watanabe A, Iwayama Y, Ohba H, Hattori E, Yamada K, Yoshikawa T.
  • Journal Title: J Neurochem. 115(6) Pages: 1374-1385
  • Peer Reviewed
• [Journal Article] Excessive ingestion of long-chain polyunsaturated fatty acids during developmental stage causes strain- and sex-dependent eye abnormalities in mice. (2010)
  • Author(s): Maekawa M, Iwayama Y, Watanabe A, Nozaki Y, Ohnishi T, Ohba H, Toyoshima M, Hamazaki K, Osumi N, Aruga J, Yoshikawa T.
  • Journal Title: Biochem Biophys Res Commun. 402(2) Pages: 431-437
  • NAID: 130004935262
  • Peer Reviewed
• [Journal Article] Giant subependymoma developed in a patient with aniridia : analyses of PAX6 and tumor-relevant genes. (2010)
  • Author(s): Maekawa M, Fujisawa H, Iwayama Y, Tamase A, Toyota T, Osumi N, Yoshikawa T.
  • Journal Title: Brain Pathol. 20(6) Pages: 1033-1041
  • Peer Reviewed
• [Journal Article] Arachidonic acid drives postnatal neurogenesis and elicits a beneficial effect on prepulse inhibition, a biological trait of psychiatric illnesses. (2010)
  • Author(s): Maekawa M, Takashima N, Matsumata M, Ikegami S, Kontani M, Hara Y, Kawashima H, Owada Y, Kiso Y, Yoshikawa T, Inokuchi K, Osumi N.
  • Journal Title: Brain Pathol. 20(6) Pages: 1033-1041
  • Peer Reviewed
• [Journal Article] Failure to confirm genetic association of the FXYD6 gene with schizophrenia: the Japanese population and meta-analysis. (2010)
  • Author(s): Iwata Y, Yamada K, Iwayama Y, Anitha A, Thanseem I, Toyota T, Hattori E, Ohnishi T, Maekawa M, Nakamura K, Suzuki K, Matsuzaki H, Tsuchiya KJ, Suda S, Sugihara G, Takebayashi K, Yamamoto S, Iwata K, Mori N, Yoshikawa T.
  • Journal Title: Am J Med Genet B Neuropsychiatr Genet. 153B(6) Pages: 1221-1227
  • Peer Reviewed
• [Journal Article] Behavioral analyses of transgenic mice harboring bipolar disorder candidate genes, IMPA1 and IMPA2. (2010)
  • Author(s): Ohnishi T, Watanabe A, Ohba H, Iwayama Y, Maekawa M, Yoshikawa T.
  • Journal Title: Neurosci Res. 67(1) Pages: 86-94
  • Peer Reviewed
• [Journal Article] Association analyses between brain-expressed fatty-acid binding protein (FABP) genes and schizophrenia and bipolar disorder. (2010)
  • Author(s): Iwayama Y, Hattori E, Maekawa M, Yamada K, Toyota T, Ohnishi T, Iwata Y, Tsuchiya KJ, Sugihara G, Kikuchi M, Hashimoto K, Iyo M, Inada T, Kunugi H, Ozaki N, Iwata N, Nanko S, Iwamoto K, Okazaki Y, Kato T, Yoshikawa T.
  • Journal Title: Am J Med Genet B Neuropsychiatr Genet. 153B(2) Pages: 484-493
  • Peer Reviewed
• [Journal Article] Polymorphism screening of brain-expressed FABP7, 5 and 3 genes and association studies in autism and schizophrenia in Japanese subjects. (2010)
  • Author(s): Maekawa M, Iwayama Y, Arai R, Nakamura K, Ohnishi T, Toyota T, Tsujii M, Okazaki Y, Osumi N, Owada Y, Mori N, Yoshikawa T.
  • Journal Title: J Hum Genet. 55(2) Pages: 127-130
  • NAID: 10030733813
  • Peer Reviewed
• [Journal Article] Analysis of strain-dependent prepulse inhibition points to a role for Shmt1 (SHMT1) in mice and in schizophrenia. (2010)
  • Author(s): Motoko Maekawa
  • Journal Title: J Neurochem. Volume: 115 Pages: 1374-85
  • Peer Reviewed
• [Journal Article] Excessive ingestion of long-chain polyunsaturated fatty acids during developmental stage causes strain- and sex-dependent eye abnormalities in mice. (2010)
  • Author(s): Motoko Maekawa
  • Journal Title: Biochem Biophys Res Commun. Volume: 402 Pages: 431-7
  • NAID: 130004935262
  • Peer Reviewed
• [Journal Article] Giant subependymoma developed in a patient with aniridia : analyses of PAX6 and tumor-relevant genes. (2010)
  • Author(s): Motoko Maekawa
  • Journal Title: Brain Pathol. Volume: 20 Pages: 1033-41
  • Peer Reviewed
• [Journal Article] Evaluation of Pax6 mutant rat as a model for autism. (2010)
  • Author(s): Toshiko Umeda
  • Journal Title: PLoS One. Volume: 5
  • Peer Reviewed
• [Journal Article] Failure to confirm genetic association of the FXYD6 gene with schizophrenia : the Japanese population and meta-analysis. (2010)
  • Author(s): Yasuhide Iwata
  • Journal Title: Am J Med Genet B Neuropsychiatr Genet. Volume: 153B Pages: 1221-7
  • Peer Reviewed
• [Journal Article] Polymorphism screening of brain-expressed FABP7, 5 and 3 genes and association studies in autism and schizophrenia in Japanese subjects (2010)
  • Author(s): Maekawa et al.
  • Journal Title: J Hum Genet (Epub a head of print)
  • NAID: 10030733813
  • Peer Reviewed
• [Journal Article] A novel missense mutation (Leu46Val) of PAX6 found in an autistic patient. (2009)
  • Author(s): Maekawa M, Iwayama Y, Nakamura K, Sato M, Toyota T, Ohnishi T, Yamada K, Miyachi T, Tsujii M, Hattori E, Maekawa N, Osumi N, Mori N, Yoshikawa T.
  • Journal Title: Neurosci Lett. 462(3) Pages: 267-271
  • Peer Reviewed
• [Journal Article] Analysis of a t(18;21)(p11.1;p11.1) translocation in a family with schizophrenia. (2009)
  • Author(s): Meerabux JM, Ohba H, Iwayama Y, Maekawa M, Detera-Wadleigh SD, DeLisi LE, Yoshikawa T.
  • Journal Title: J Hum Genet. 54(7) Pages: 386-391
  • NAID: 10030730942
  • Peer Reviewed
• [Journal Article] NMDA receptor antagonist memantine promotes cell proliferation and production of mature granule neurons in the adult hippocampus. (2009)
  • Author(s): Maekawa M, Namba T, Suzuki E, Yuasa S, Kohsaka S, Uchino S.
  • Journal Title: Neurosci Res. 63(4) Pages: 259-266
  • Peer Reviewed
• [Journal Article] Association analyses between brain-expressed fatty-acid binding protein(FABP)genes and schizophrenia and bipolar disorder (2009)
  • Author(s): Iwayama et al.
  • Journal Title: Am J Med Genet B Neuropsychiatr Genet 153B(2) Pages: 484-493
  • Peer Reviewed
• [Journal Article] Arachidonic acid drives postnatal neurogenesis and elicits a beneficial of feet on prepulse inhibition, a biological trait of psychiatric illnesses (2009)
  • Author(s): Maekawa et al.
  • Journal Title: PLoS One 4(4)
  • Peer Reviewed
• [Presentation] NMDA receptor and schizophrenia-from the perspective of neurogenesis (2009)
  • Author(s): 前川素子、難波隆志、内野茂夫、高坂新一、吉川武男
  • Organizer: 日本神経科学学会
  • Place of Presentation: 名古屋
  • Year and Date: 2009-09-16
• [Presentation] マウス系統間のプレパルス抑制の違いはD-セリン代謝系に関係する (2009)
  • Author(s): 前川素子、吉川武男
  • Organizer: 日本脳科学会
  • Place of Presentation: 金沢
  • Year and Date: 2009-06-12