Sugar modification system that inhibits regeneration of injured CNS neurons

• Project/Area Number: 23590221
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General anatomy (including Histology/Embryology)
• Research Institution: Nara Medical University
• Principal Investigator: WANAKA Akio 奈良県立医科大学, 医学部, 教授 (90210989)
• Co-Investigator(Kenkyū-buntansha): TATSUMI Kouko 奈良県立医科大学, 医学部, 准教授 (90208033) ; OKUDA Hiroaki 奈良県立医科大学, 医学部, 助教 (40453162)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000); Fiscal Year 2013: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2011: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
• Keywords: OASIS / コンドロイチン硫酸 / 神経再生 / アストロサイト / 転写調節 / ノックアウトマウス / 脳損傷 / 糖鎖修飾 / C6ST-1 / 転写因子

Research Abstract

We found that chondroitin sulfate proteoglycan expression is reduced in the OASIS-kockout mouse as compared to the wild type mouse. We screened that target genes of OASIS transcription in the CSPG production pathway and found that C6ST-1, an enzyme that transfers sulfate moieties to CSPG, was a potential candidate. By artificial transcription assay system, we examined whether C6ST-1 transcription is regulated by OASIS or not. The first intron of the C6ST-1 genome contained several CRE (OASIS binding site) and deletion of those CREs reduced C6ST-1 transcription. Taken together, we concluded that OASIS inhibits neuronal regeneration by regulating C6ST-1 activities in the injured central nervous system.

Research Products

• [Journal Article] Geissoschizine methyl ether, an alkaloid from the Uncaria hook, improves remyelination after cuprizone-induced demyelination in medial prefrontal cortex of adult mice. (2014)
  • Author(s): Morita S, Tatsumi K, Makinodan M, Okuda H, Kishimoto T, Wanaka A.
  • Journal Title: Neurochem Res. Volume: 39 Issue: 1 Pages: 59-67
  • DOI: 10.1007/s11064-013-1190-1
  • Peer Reviewed
• [Journal Article] Chondroitin sulfate proteoglycan tenascin-R regulates glutamate uptake by adult brain astrocytes (2014)
  • Author(s): Okuda H, Tatsumi K, Morita S, Shibukawa Y, Korekane H, Horii-Hayashi N, Wada Y, Taniguchi N, Wanaka A.
  • Journal Title: J Biol Chem Volume: 289 Issue: 5 Pages: 2620-2631
  • DOI: 10.1074/jbc.m113.504787
  • Peer Reviewed / Open Access
• [Journal Article] Inhibition of Wnt/β-catenin pathway by Dikkopf-1 affects midfacial morphogenesis in chick embryo. (2014)
  • Author(s): Kawakami M, Okuda H, Tatsumi K, Kirita T, Wanaka A.
  • Journal Title: J Biosci Bioeng. Volume: 117 Issue: 6 Pages: 664-669
  • DOI: 10.1016/j.jbiosc.2013.11.015
  • NAID: 110009823147
  • Peer Reviewed
• [Journal Article] OASIS regulates chondroitin 6-O-sulfotransferase 1 gene transcription in the injured adult mouse cerebral cortex (2014)
  • Author(s): Okuda H, Tatsumi K, Horii-Hayashi N, Morita S, Okuda-Yamamoto A, Imaizumi K, Wanaka A
  • Journal Title: J Neurochem Volume: Epub ahead Issue: 5 Pages: 612-25
  • DOI: 10.1111/jnc.12736
  • Peer Reviewed
• [Journal Article] Chondroitin sulfate proteoglycan tenascin-R regulates glutamate uptake by adult brain astrocytes (2013)
  • Author(s): Okuda H, Tatsumi K, Morita S, Shibukawa Y, Korekane H, Horii-Hayashi N, Wada Y, Taniguchi N, Wanaka A
  • Journal Title: J. Biol Chem Volume: (in press)
  • Peer Reviewed
• [Journal Article] Inhibition of Wnt/beta-catenin pathway by Dickkopf-1 affects midfacial morphogenesis in chick embryo (2013)
  • Author(s): Kawakami M, Okuda H, Tatsumi K, Kirita T, Wanaka A
  • Journal Title: J. Biosci. Bioeng Volume: (in press)
  • Peer Reviewed
• [Journal Article] Geissoschizine Methyl Ether, an Alkaloid from the Uncaria Hook, Improves Remyelination after Cuprizone-induced Demyelination in Medial Prefrontal Cortex of Adult Mice (2013)
  • Author(s): Morita S, Tatsumi K, Makinodan M, Okuda, H, Kishimoto T, Wanaka A
  • Journal Title: Neurochem. Res Volume: (in press)
  • Peer Reviewed
• [Journal Article] Induction of inner ear hair cell-like cells from Math1-transfected mouse ES cells (2013)
  • Author(s): Ouji Y, Ishizaka S, Nakamura-Uchiyama F, Wanaka A, Yoshikawa M
  • Journal Title: Cell Death Dis Volume: 4 (epub ahead)
  • Peer Reviewed
• [Journal Article] Oligodendrocyte plasticity with an intact cell body in vitro (2013)
  • Author(s): Makinodan M, Okuda-Yamamoto A, Ikawa D, Toritsuka M, Takeda T, Kimoto S, Tatsumi K, Okuda H, Nakamura Y, Wanaka A, Kishimoto T
  • Journal Title: PLoS One Volume: 8 (epub)
  • Peer Reviewed
• [Journal Article] Changes in pericytic expression of NG2 and PDGFRB and vascular permeability in the sensory circumventricular organs of adult mouse by osmotic stimulation (2013)
  • Author(s): Morita S, Hourai A, Miyata S
  • Journal Title: Cell Biochem Funct Volume: (Epub ahead of print) Issue: 1 Pages: 51-61
  • DOI: 10.1002/cbf.2971
  • Peer Reviewed
• [Journal Article] Astrocytic TRPV1 ion channels detect blood-borne signals in the se sory circumventricular organs of adult mouse brains (2013)
  • Author(s): Mannari T, Morita S, Furube E, Tominaga M, Miyata S
  • Journal Title: Glia Volume: 61(6) Pages: 957-971
  • Peer Reviewed
• [Journal Article] VEGF-dependent continuous angiogenesis in the median eminence of adult mice (2013)
  • Author(s): Morita S, Ukai S, Miyata S
  • Journal Title: Eur J Neurosci Volume: 37(4) Pages: 508-518
  • Peer Reviewed
• [Journal Article] Oligodendrocyte plasticity with an intact cell body in vitro. (2013)
  • Author(s): Makinodan M, Okuda-Yamamoto A, Ikawa D, Toritsuka M, Takeda T, Kimoto S, Tatsumi K, Okuda H, Nakamura Y, Wanaka A, Kishimoto T
  • Journal Title: PLoS One. Volume: 8 Issue: 6 Pages: e66124-e66124
  • DOI: 10.1371/journal.pone.0066124
  • Peer Reviewed
• [Journal Article] Induction of inner ear hair cell-like cells from Math1-transfected mouse ES cells. (2013)
  • Author(s): Ouji Y, Ishizaka S, Nakamura-Uchiyama F, Wanaka A, Yoshikawa M.
  • Journal Title: Cell Death Dis. Volume: 4 Issue: 7 Pages: e700-e700
  • DOI: 10.1038/cddis.2013.230
  • Peer Reviewed
• [Journal Article] Gliosis-specific transcription factor OASIS coincides with proteoglycan core protein genes in the glial scar and inhibits neurite outgrowth (2012)
  • Author(s): Iseki K, Hagino S, Nikaido T, Zhang Y, Mori T, Yokoya S, Hozumi Y, Goto K, Wanaka A, Tase C
  • Journal Title: Biomed Res Volume: 33(6) Pages: 345-353
  • NAID: 130004903839
  • Peer Reviewed
• [Journal Article] Distinct cellular distributions of Kv4 pore-forming and auxiliary subunits in rat dorsal root ganglion neurons (2012)
  • Author(s): Matsuyoshi H, Takimoto K, Yunoki T, Erickson VL, Tyagi P, Hirao Y, Wanaka A, Yoshimura N
  • Journal Title: Life Sci Volume: 91(7-8) Pages: 258-263
  • Peer Reviewed
• [Journal Article] Different vascular permeability between the sensory and secretory circumventricular organs of adult mouse brain (2012)
  • Author(s): Morita S, Miyata S
  • Journal Title: Cell Tissue Res Volume: 349(2) Pages: 589-603
• [Journal Article] Overexpression of IgLON cell adhesion molecules changes proliferation and cell size of cortical astrocytes (2012)
  • Author(s): Sugimoto C, Morita S, Miyata S
  • Journal Title: Cell Biochem Funct Volume: 30(5) Pages: 400-405
  • Peer Reviewed
• [Journal Article] Gliosis-specific transcription factor OASIS coincides with proteoglycan core protein genes in the glial scar and inhibits neurite outgrowth. (2012)
  • Author(s): Iseki K, Hagino S, Nikaido T, Zhang Y, Mori T, Yokoya S, Hozumi Y, Goto K, Wanaka A, Tase C.
  • Journal Title: Biomedical Research Volume: 33 Pages: 343-353
  • NAID: 130004903839
  • Peer Reviewed
• [Journal Article] Distinct cellular distributions of Kv4 pore-forming and auxiliary subunits in rat dorsal root ganglion neurons. (2012)
  • Author(s): Matsuyoshi H, Takimoto K, Yunoki T, Erickson VL, Tyagi P, Hirao Y, Wanaka A, Yoshimura N.
  • Journal Title: Life Sciences Volume: 91 Pages: 258-263
  • Peer Reviewed
• [Journal Article] Olanzapine stimulates proliferation but inhibits differentiation in rat oligodendrocyte precursor cell cultures (2011)
  • Author(s): Kimoto S, Okuda A, Toritsuka M, Yamauchi T, Makinodan M, Okuda H, Tatsumi K, Nakamura Y, Wanaka A, Kishimoto T
  • Journal Title: Prog Neuropsychopharmacol Biol Psychiatry Volume: 35(8) Pages: 1950-1956
  • Peer Reviewed
• [Journal Article] Distinct mechanisms are responsible for osteopenia and growth retardation in OASIS-deficient mice (2011)
  • Author(s): Murakami T, Hino S, Nishimura R, Yoneda T, Wanaka A, Imaizumi K
  • Journal Title: Bone Volume: 48(3) Pages: 514-523
  • Peer Reviewed
• [Journal Article] Environmental stimulation changes tissue-type plasminogen activator activity in the adult mouse hippocampus (2011)
  • Author(s): Horii-Hayashi N, Yoshikawa M, Matsusue Y, Ishizaka S, Nishi M, Wanaka A
  • Journal Title: Neurochem Int Volume: 58(1) Pages: 1-4
  • Peer Reviewed
• [Journal Article] Effect of pleiotrophin on glutamate-induced neurotoxicity in cultured hippocampal neurons (2011)
  • Author(s): Asai H, Morita S, Miyata S
  • Journal Title: Cell Biochem Funct Volume: 29(8) Pages: 660-665
  • Peer Reviewed
• [Journal Article] A new method for visualization of endothelial cells and extravascular leakage in adult mouse brain using fluorescein isothiocyanate (2011)
  • Author(s): Miyata S, Morita S
  • Journal Title: J Neurosci Methods Volume: 202(1) Pages: 9-16
  • Peer Reviewed
• [Journal Article] Localization of plasminogen in mouse hippocampus, cerebral cortex, and hypothalamus (2011)
  • Author(s): Taniguchi Y, Inoue N, Morita S, Nikaido Y, Nakashima T, Nagai N, Okada K, Matsuo O, Miyata S
  • Journal Title: Cell Tissue Res Volume: 343(2) Pages: 303-317
  • Peer Reviewed
• [Journal Article] Olanzapine stimulates proliferation but inhibits differentiation in rat oligodendrocyte precursor cell cultures. (2011)
  • Author(s): Kimoto S, Okuda A, Toritsuka M, Yamauchi T, Makinodan M, Okuda H, Tatsumi K, Nakamura Y, Wanaka A, Kishimoto T.
  • Journal Title: Prog Neuropsychopharmacol Biol Psychiatry Volume: 35 Issue: 8 Pages: 1950-1956
  • DOI: 10.1016/j.pnpbp.2011.07.011
  • Peer Reviewed
• [Journal Article] Distinct mechanisms are responsible for osteopenia and growth retardation in OASIS-deficient mice. (2011)
  • Author(s): Murakami T, Hino S, Nishimura R, Yoneda T, Wanaka A, Imaizumi K.
  • Journal Title: Bone Volume: 48 Issue: 3 Pages: 514-523
  • DOI: 10.1016/j.bone.2010.10.176
  • Peer Reviewed
• [Journal Article] Environmental stimulation changes tissue-type plasminogen activator activity in the adult mouse hippocampus (2011)
  • Author(s): Horii-Hayashi N, Yoshikawa M, Matsusue Y, Ishizaka S, Nishi M, Wanaka A
  • Journal Title: Neurochemistry International Volume: 58 Issue: 1 Pages: 1-4
  • DOI: 10.1016/j.neuint.2010.10.007
  • Peer Reviewed
• [Presentation] 神経活動にともなうアストロサイトの形態変化 (2014)
  • Author(s): 辰巳晃子
  • Organizer: 第119回日本解剖学会総会・シンポジウム(グリア細胞研究の最前線)
  • Place of Presentation: 自治医科大学
• [Presentation] Inhibition of astrocyte metabolisms in the basal ganglionic nuclei lowers voluntary motor activities in adult mice (2013)
  • Author(s): 辰巳晃子
  • Organizer: 第118回日本解剖学会総会
  • Place of Presentation: 香川国際会議場(高松)
• [Presentation] Astrocytic morphologies in the basal ganglionic nuclei are closely related to motor activities in adult mice (2013)
  • Author(s): 辰巳晃子
  • Organizer: 第36回日本神経科学大会、第56回日本神経化学会大会,第23回日本神経回路学会合同学会
  • Place of Presentation: 京都国際会議場
• [Presentation] Voluntary exercise promotes astrogliogenesis from Olig2 cells in some nuclei of the basal ganglia of adult mouse (2012)
  • Author(s): 辰巳晃子
  • Organizer: 第117回日本解剖学会総会
  • Place of Presentation: 山梨大学
• [Presentation] 妊娠期高脂肪食摂取が仔の多動を引き起こす。 (2012)
  • Author(s): 山野眞利子、林美幸、奥田洋明、和中明生
  • Organizer: 第35回日本神経科学大会
  • Place of Presentation: 名古屋市
• [Presentation] TenascinR陽性アストロサイトは新規細胞外マトリックスを構成する。 (2012)
  • Author(s): 奥田洋明、辰巳晃子、渋川幸直、是金宏昭、林－堀井謹子、和田芳直、谷口直之、和中明生
  • Organizer: 第35回日本神経科学大会
  • Place of Presentation: 名古屋市
• [Presentation] TenascinR constitutes a unique extracellular matrix and modulates GLAST expression in astrocytes. (2012)
  • Author(s): Okuda H, Tatsumi K, Shibukawa Y, Korekane H, Horii-Hayashi N, Wada Y, Taniguchi N, Wanaka A
  • Organizer: 第53回日本神経化学会大会、第11回アジア太平洋神経化学会議 合同大会
  • Place of Presentation: 神戸市
• [Presentation] Voluntary exercise promotes astrogliogenesis from Olig2 cells in the subthalamic nucleus of adult mouse (2011)
  • Author(s): 辰巳晃子
  • Organizer: 第116回日本解剖学会総会第88回日本生理学会合同
  • Place of Presentation: パシフィコ横浜 (震災により誌上開催)
• [Presentation] Voluntary exercise promotes astrogliogenesis from Olig2 cells in some nuclei of the basal ganglia of adult mouse (2011)
  • Author(s): 辰巳晃子
  • Organizer: 第54回日本神経化学会
  • Place of Presentation: 加賀山代
• [Presentation] 成体マウス網膜でのOlig2の発現パターン (2011)
  • Author(s): 後岡 克典、辰巳 晃子、奥田 洋明、緒方 奈保子、和中 明生
  • Organizer: 第54回日本神経化学会
  • Place of Presentation: 金沢
• [Presentation] Voluntary exerciseは大脳基底核におけるOlig2細胞のアストロサイト分化を促 進する (2011)
  • Author(s): 辰巳 晃子、奥田 洋明 、山野 眞利子、和中 明生
  • Organizer: 第54回日本神経化学会
  • Place of Presentation: 金沢