Effects of brain niche constituents on differentiation and survival of neural cells containing oligodendrocytes

2009 Fiscal Year Final Research Report

• Project/Area Number: 19390292
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Embryonic/Neonatal medicine
• Research Institution: Aichi Medical University
• Principal Investigator: OOHIRA Atsuhuko Aichi Medical University, 客員教授 (20101074)
• Co-Investigator(Renkei-kenkyūsha): NAKANISHI Keiko 愛知県心身障害者コロニー, 発達障害研究所, 主任研究員 (50280813)
• Project Period (FY): 2007 – 2009
• Keywords: 未熟児 / 脳障害 / 子宮内胎児発育遅延 / 低酸素 / コンドロイチン硫酸 / 増殖因子 / オリゴデンドロサイト / 神経細胞

Research Abstract

The final goal of our research is to conquer brain injuries often found in the premature newborn. As the experimental model, we produced fetal growth retardation (FGR) model rats. The FGR pups exhibited a significant delay in postnatal neurological development, a high density of apoptotic cells in the cortical plate, and a reduced amount of brain chondroitin sulfate proteoglycans that is a major brain niche constituent. Hypoxic treatment of a neural cell mixture which differentiated from neural stem cells in culture revealed that neuronal cells were more sensitive to hypoxia than oligodendrocytes. Addition of fibroblast growth factor-2 or epidermal growth factor to the hypoxic culture reduced cell death, suggesting that these growth factors are promising to prevent cell death found in the cortical plate of the FGR rat newborn.

Research Products

• [Journal Article] Chondroitin sulfate, a major niche substance of neural stem cells, and cell transplantation therapy of neurodegeneration combined with niche modification. (2009)
  • Author(s): Yoshiaki Sato, Atsuhiko Oohira
  • Journal Title: Current Stem Cell Research and Therapy Vol.4,No.3 Pages: 200-209
  • Peer Reviewed
• [Journal Article] Behavioral abnormalities of fetal growth retardation model rats with reduced amounts of brain proteoglycans. (2009)
  • Author(s): Akiko Saito, Fumiko Matsui, Kanako Hayashi, Mimi Watanabe, Yuko Ichinohashi, Yoshiaki Sato, Masahiro Hayakawa, Seiji Kojima, Atsuhiko Oohira
  • Journal Title: Experimental Neurology Vol.219,No.1 Pages: 81-92
  • Peer Reviewed
• [Journal Article] A highly sulfated chondroitin sulfate preparation, CS-E, prevents excitatory amino acid-induced neuronal cell death. (2008)
  • Author(s): Yoshiaki Sato, Keiko Nakanishi, Yoshihito Tokita, Hiroko Kakizawa, Michiru Ida, Hiroshi Maeda, Fumiko Matsui, Sachiko Aono, Akiko Saito, Yoshiyuki Kuroda, Masahiro Hayakawa, Seiji Kojima, Atsuhiko Oohira
  • Journal Title: Journal of Neurochemistry Vol.104,No.6 Pages: 1565-1576
  • Peer Reviewed
• [Journal Article] Reduction of brain injury in neonatal hypoxic-ischemic rats by intracerebroventricular injection of neural stem/progenitor cells together with chondroitinase ABC. (2008)
  • Author(s): Yoshiaki Sato, Keiko Nakanishi, Masahiro Hayakawa, Hiroko Kakizawa, Akiko Saito, Yoshiyuki Kuroda, Michiru Ida, Yoshihito Tokita, Sachiko Aono, Fumiko Matsui, Seiji Kojima, Atsuhiko Oohira
  • Journal Title: Reproductive Sciences Vol.15,No.6 Pages: 613-620
  • Peer Reviewed
• [Journal Article] Ectodomain shedding of neuroglycan C, a brain-specific chondroitin sulfate proteoglycan, by TIMP-2- and TIMP-3-sensitive proteolysis. (2007)
  • Author(s): Takuya Shuo, Sachiko Aono, Keiko Nakanishi, Yoshihito Tokita, Yoshiyuki Kuroda, Michiru Ida, Fumiko Matsui, Hiroko Maruyama, Toshiyuki Kaji, Atsuhiko Oohira
  • Journal Title: Journal of Neurochemistry Vol.102,No.5 Pages: 1561-1568
  • Peer Reviewed
• [Journal Article] Neuroglycan C, a brain-specific chondroitin sulfate proteoglycan, interacts with pleiotrophin, a heparin-binding growth factor.
  • Author(s): Keiko Nakanishi, Yoshihito Tokita, Sachiko Aono, Michiru Ida, Fumiko Matsui, Yoichiro Higashi, Atsuhiko Oohira
  • Journal Title: Neurochemical Research (in press)
  • Peer Reviewed
• [Presentation] Search for the binding protein of neuroglycan C, a brain-specific chondroitin sulfate proteoglycan. (2009)
  • Author(s): Keiko Nakanishi, et al.
  • Organizer: 36^<th> International Congress of Physiological Sciences
  • Place of Presentation: Kyoto
  • Year and Date: 2009-07-28
• [Presentation] 中枢神経組織の損傷修復と細胞環境分子コンドロイチン硫酸 (2008)
  • Author(s): 大平敦彦
  • Organizer: 新生児慢性肺疾患研究会学術集会, (特別講演)
  • Place of Presentation: 名古屋
  • Year and Date: 2008-11-15
• [Presentation] 神経幹細胞を用いた新生児低酸素性虚血性脳症治療の可能性(シンポジウム「脳性麻痺は防止できるか」) (2008)
  • Author(s): 伊田みちる, 他
  • Organizer: 日本周産期・新生児医学学術集会
  • Place of Presentation: 横浜
  • Year and Date: 2008-07-14
• [Book] 脳の損傷修復の鍵となる糖鎖, 第3の生命鎖 : 糖鎖の謎が今、解る(古川鋼一編) (2009)
  • Author(s): 大平敦彦
  • Total Pages: 22-29
  • Publisher: (株)クバプロ
• [Book] Chondroitin sulfate proteoglycans : a key substance for central nervous system injury repair.In"Experimental Glycoscience"(ed.by N.Taniguchi, et al.) (2008)
  • Author(s): Atsuhiko Oohira
  • Total Pages: 195-198
  • Publisher: Springer
• [Book] Multiple species and functions of proteoglycans in the central nervous system.In "Comprehensive Glycoscience : From Chemistry to System Biology"(ed.by J.P.Kamerling.) (2007)
  • Author(s): Atsuhiko Oohira
  • Total Pages: 297-322
  • Publisher: Elsevier
• [Remarks] 新生児脳障害に新治療法 : 細胞死防止の効果.中日新聞、2008.5.10.
• [Remarks] 脳損傷修復 : 高硫酸化CS-Eが興奮性神経細胞死を抑制(疾患に対する糖鎖の生物学的役割に関する最新知見)Medical Tribune, 2008.4.10.