hnRNPA1 as a new neural cell differentiation development regulator -Aim at psychiatric disorder medical treatment-

• Project/Area Number: 24700358
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Nerve anatomy/Neuropathology
• Research Institution: Fujita Health University
• Principal Investigator: MANABE Takayuki 藤田保健衛生大学, 総合医科学研究所, 准教授 (90382283)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2013: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000); Fiscal Year 2012: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 神経発生・分化・異常 / 精神疾患 / hnRNPA1 / オリゴデンドロサイト / 統合失調症 / スプライシング

Research Abstract

Alternative pre-mRNA splicing is a fundamental strategy for eukaryotes to provide a substantial complexity in proteome from the limited genome size. It must be precisely controlled to ensure their proper physiological functions, and thus disorders in this process often end up in serious diseases. There have been accumulating reports of aberrant splicing in the related genes in Schizophrenia (SZ), however, not much study has been carried out with regard to a splicing abnormality implicated in this disease. We have postulated that the aberrant expression of hnRNPA1, as a global splicing silencer, is involved in the pathology of SZ.
Remarkably, we have obtained evidence supporting that the disturbed expression of the hnRNPA1 causes maturation defects of oligodendrocytes through aberrant splicing of SZ-related genes. These results are the first to demonstrate the role of hnRNPA1 in the development of glial cells via control of the related alternative splicing.

Research Products

• [Journal Article] Fluvoxamine moderates reduced voluntary activity following chronic dexamethasone infusion in mice via (2014)
  • Author(s): Terada K, Izumo N, Suzuki B, Karube Y, Morikawa T, Ishibashi Y, Kameyama T, Chiba K, Sasaki N, Iwata K,
  • Journal Title: Neurochemistry International Volume: 69 Pages: 9-13
  • DOI: 10.1016/j.neuint.2014.02.002
  • Peer Reviewed
• [Journal Article] The human oligodendrocyte proteome. (2013)
  • Author(s): Iwata K, Café-Mendes CC, Schmitt A, Steiner J, Manabe T, Matsuzaki H, Falkai P, Turck CW, Martins-de-
  • Journal Title: Proteomis Volume: 13 Issue: 23-24 Pages: 3548-3663
  • DOI: 10.1002/pmic.201300201
  • Peer Reviewed
• [Journal Article] 統合失調症における選択的スプライシング調節の破綻 (2013)
  • Author(s): 眞部孝幸、森川智美
  • Journal Title: 藤田学園医学会誌 Volume: 37巻 Pages: 15-20
• [Journal Article] 統合失調症における選択的スプライシング調節の破綻 (2013)
  • Author(s): 眞部孝幸,森川智美
  • Journal Title: 藤田学園医学会誌 Volume: 37 Pages: 15-20
• [Journal Article] Trans-mesenteric neural crest cells are the principal source of the colonic enteric nervous system. (2012)
  • Author(s): Nishiyama, C., Uesaka, T., Manabe, T., Yonekura, Y., Nagasawa, T., Newgreen, D.F., Young, H.M., *Enomoto, H.
  • Journal Title: Nat. Neurosci. Volume: 15(9) Issue: 9 Pages: 1211-1218
  • DOI: 10.1038/nn.3184
  • Peer Reviewed
• [Journal Article] Vldlr overexpression causes hyperactivity in rats. (2012)
  • Author(s): Iwata K
  • Journal Title: Mol Autism. Volume: 3 Issue: 1 Pages: 11-11
  • DOI: 10.1186/2040-2392-3-11
  • Peer Reviewed
• [Journal Article] Triggers for Autism: genetic and environmental factors (2012)
  • Author(s): Matsuzaki H, Iwata K, Manabe T, Mori N
  • Journal Title: Journal of Central Nervous System Disease Volume: 4 Pages: 1-10
  • DOI: 10.4137/jcnsd.s9058
  • Peer Reviewed
• [Journal Article] Decreased voluntary activity and amygdala levels of serotonin and dopamine in ovariectomized rats (2012)
  • Author(s): Izumo N, Ishibashi Y, Ohba M, Morikawa T and Manabe T.
  • Journal Title: Behavioural Brain Research Volume: 227巻 Issue: 1 Pages: 1-6
  • DOI: 10.1016/j.bbr.2011.10.031
  • Peer Reviewed