Analysis of DACS, novel matrix structure composed of chondroitin sulfate proteoglycan in the brain

• Project/Area Number: 24592141
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Cerebral neurosurgery
• Research Institution: Nara Medical University
• Principal Investigator: OKUDA Hiroaki 奈良県立医科大学, 医学部, 助教 (40453162)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2014: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2012: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
• Keywords: アストロサイト / コンドロイチン硫酸プロテオグリカン / 細胞外マトリックス / コンドロイチン硫酸 / グルタミン酸 / CSPG

Outline of Final Research Achievements

In our previous study, the CS-56 antibody, which recognizes a chondroitin sulfate moiety, labeled a subset of adult brain astrocytes, yielding a patchy extracellular matrix pattern. To explore the molecular nature of CS-56-labeled glycoproteins, we purified glycoproteins of the adult mouse cerebral cortex using a combination of chromatographies. One of the purified proteins was identified as tenascin-R (TNR) by mass spectrometric analysis. When we compared TNR mRNA expression patterns with the distribution patterns of CS-56-positive cells, TNR mRNA was detected in CS-56-positive astrocytes. TNR knockdown by siRNA expression significantly reduced glutamate uptake in cultured astrocytes. Furthermore, expression of mRNA and protein of GLAST, which is a major component of astrocytic glutamate transporters, was reduced by TNR knockdown. Our results suggest that TNR is expressed in a subset of astrocytes and contributes to glutamate homeostasis by regulating astrocytic GLAST expression.

Research Products

• [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
• [Presentation] Tenascin R陽性アストロサイトにおけるグルタミン酸取り込み能の調節 (2013)
  • Author(s): 奥田 洋明・辰巳 晃子・森田 晶子・渋川 幸直・是金 宏昭・堀井-林 謹子・和田 芳直・谷口 直之・和中 明生
  • Organizer: 第118回日本解剖学会総会
  • Place of Presentation: 香川
• [Presentation] TenascinR-positive astrocytes constitutes a unique extracellular matrix and delineates the astrocytic territories. (2012)
  • Author(s): Hiroaki Okuda, Kouko Tatsumi, Yukinao Shibukawa, Hiroaki Korekane, Noriko Horii-Hayashi, Yoshinao Wada, Naoyuki Taniguchi, Akio Wanaka
  • Organizer: 第35回日本神経科学大会
  • Place of Presentation: 名古屋
• [Presentation] TenascinR constitutes a unique extracellular matrix and modulates GLAST expression in astrocytes. (2012)
  • Author(s): Hiroaki Okuda, Kouko Tatsumi, Yukinao Shibukawa, Hiroaki Korekane, Noriko Horii-Hayashi, Yoshinao Wada, Naoyuki Taniguchi, Akio Wanaka
  • Organizer: 第55回日本神経化学会
  • Place of Presentation: 神戸