Possible role of glial cells in the progression of Alzheimer's disease pathology

2009 Fiscal Year Final Research Report

• Project/Area Number: 18500279
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Nerve anatomy/Neuropathology
• Research Institution: Saitama Medical University
• Principal Investigator: MORI Takashi Saitama Medical University, 医学部, 准教授 (60239605)
• Co-Investigator(Kenkyū-buntansha): YAMAGUCHI Haruyasu 群馬大学, 医学部, 教授 (00158114) ; ASANO Takao 埼玉医科大学, 医学部, 客員教授 (70090496)
• Project Period (FY): 2006 – 2009
• Keywords: 神経科学 / 脳神経変性疾患 / 神経病理学 / 細胞・組織 / 獣医学

Research Abstract

Here, we aimed to examine the possible role of astrocyte-derived S100B in the progression of Alzheimer's disease pathology. First, using Alzheimer's disease model mice, we showed that Alzheimer's disease-like pathology was significantly ameliorated by the treatment of arundic acid [(R)-(-)-2-propyloctanoic acid], which is known to negatively regulate astrocyte synthesis of S100B. Subsequently, to dissect the relationship between S100B and Alzheimer's disease-like pathology, we took a genetic approach by crossing transgenic mice expressing human S100B with Alzheimer's disease model mice. We demonstrated evidence that (over)-expression of S100B acts to accelerate Alzheimer's disease-like pathology. Taken together, these data suggest that inhibiting astrocytic activation by blocking S100B biosynthesis may be a promising therapeutic strategy to delay Alzheimer's disease progression.

Research Products

• [Journal Article] Terrence Town. Overexpression of human S100B exacerbates cerebral amyloidosis and gliosis in the Tg2576 mouse model of Alzheimer's disease. (2010)
  • Author(s): Takashi Mori, Naoki Koyama, Gary W. Arendash, Yuko Horikoshi-Sakuraba, Jun Tan
  • Journal Title: Glia 58(3) Pages: 300-314
  • Peer Reviewed
• [Journal Article] Huntington Potter. Caffeine suppresses amyloid-βlevels in plasma and brain of Alzheimer's disease transgenic mice. (2009)
  • Author(s): Chuanhai Cao, John R. Cirrito, Xiaoyang Lin, Lilly Wang, Deborah K. Verges, Alexander Dickson, Malgorzata B. Mamcarz, Chi Zhang, Takashi Mori, Gary W. Arendash, David M. Holtzman
  • Journal Title: J Alzheimer's Dis 17(3) Pages: 681-697
  • Peer Reviewed
• [Journal Article] Huntington Potter. Caffeine reverses cognitive impairment and decreases brain amyloid-βlevels in aged Alzheimer's disease mice. (2009)
  • Author(s): Gary W. Arendash, Takashi Mori, Chuanhai Cao, Malgorzata B. Mamcarz, Melissa J. Runfeldt, Alexander Dickson, Kavon Rezai-Zadeh, Jun Tan, Bruce A. Citron, Xiaoyang Lin, Valentina Echeverria
  • Journal Title: J Alzheimer's Dis 17(3) Pages: 661-680
  • Peer Reviewed
• [Journal Article] Richard A. Flavell. Blocking TGF-β/SMAD 2/3 innate immune signaling mitigates Alzheimer-like pathology. (2008)
  • Author(s): Terrence Town, Yasmina Laouar, Christopher Pittenger, Takashi Mori, Christine A. Szekely, Jun Tan, Ronald S. Duman
  • Journal Title: Nat Med 14(6) Pages: 681-687
  • Peer Reviewed
• [Journal Article] Jun Tan. Peripherally administered human umbilical cord blood cells reduce parenchymal and vascular β-amyloid deposits and suppress CD40-CD40L interaction. (2008)
  • Author(s): William V. Nikolic, Huayan Hou, Terrence Town, Yuyan Zhu, Brian Giunta, Cyndy D. Sanberg, Jin Zeng, Deyan Luo, Jared Ehrhart, Takashi Mori, Paul R. Sanberg
  • Journal Title: Stem Cells Dev 17(3) Pages: 423-440
  • Peer Reviewed
• [Journal Article] Terrence Town, Jun Tan. CD40L disruption enhances Aβvaccine-mediated reduction of cerebral amyloidosis while minimizing cerebral amyloid angiopathy and inflammation. (2008)
  • Author(s): Demian F. Obregon, Huayan Hou, Yun Bai, William Nikolic, Takashi Mori, Deyan Luo, Jin Zeng, Jared Ehrhart, Frank Fernandez, Dave Morgan, Brian Giuntan
  • Journal Title: Neurobiol Dis 29(2) Pages: 336-353
  • Peer Reviewed
• [Journal Article] Enhanced cognitive activity-over and above social or physical activity- is required to protect Alzheimer's mice against cognitive impairment, reduce Aβdeposition, and increase synaptic immunoreactivity. (2007)
  • Author(s): Jennifer R. Cracchiolo, Takashi Mori, Stanley J. Nazian, Jun Tan, Huntington Potter, Gary W. Arendash.
  • Journal Title: Neurobiol Learn Mem 88(3) Pages: 277-294
  • Peer Reviewed
• [Journal Article] Transcutaneous β-amyloid peptide immunization reduces cerebral β-amyloid deposits without T cell infiltration and microhemorrhage. (2007)
  • Author(s): William V. Nikolic, Yun Bai, Demian F. Obregon, Huayan Hou, Takashi Mori, Jin Zeng, Jared Ehrhart, R. Douglas Shytle, Brian Giunta, Dave Morgan, Terrence Town, Jun Tan.
  • Journal Title: Proc Natl Acad Sci U.S.A. 104(7) Pages: 2507-2512
  • Peer Reviewed
• [Journal Article] Arundic acid ameliorates cerebral amyloidosis and gliosis in Alzheimer transgenic mice. (2006)
  • Author(s): Takashi Mori, Terrence Town, Jun Tan, Nobumichi Yada, Yuko Horikoshi, Junki Yamamoto, Taiji Shimoda, Yoshihisa Kamanaka, Narito Tateishi, Takao Asano
  • Journal Title: J Pharmacol Exp Ther 318(2) Pages: 571-578
  • Peer Reviewed
• [Presentation] ヒトS100B蛋白の過剰発現はアルツハイマー様病態(脳アミロイド症・グリオーシス)を増悪させる. (2009)
  • Author(s): 小山直基, 堀越(櫻庭)優子, 森隆
  • Organizer: 第147回日本獣医学会学術集会
  • Place of Presentation: (栃木, 日本)
  • Year and Date: 2009-04-03
• [Presentation] Terrence Town. Overexpression of S100B exacerbates cerebral amyloidosis and gliosis in the Tg2576 mouse model of Alzheimer's disease. (2008)
  • Author(s): Takashi Mori, Jun Tan, Yoshiko Nojima, Naoki Koyama, Yuko Horikoshi-Sakuraba, Masamitsu Hoshikawa, Rika Shinagawa, Yoshihisa Kamanaka, Gary W. Arendash
  • Organizer: 38th Annual Meeting of Society for Neuroscience
  • Place of Presentation: Washington D.C., U.S.A.
  • Year and Date: 2008-11-18
• [Presentation] A new therapeutic agent for Alzheimer disease: Arundic acid (ONO-2506) attenuates cerebral amyloidosis and gliosis in Alzheimer transgenic mice. (2007)
  • Author(s): Takashi Mori, Terrence Town, Jun Tan, Nobumichi Yada, Junki Yamamoto, Masamitsu Hoshikawa, Rika Shinagawa, Yoshihisa Kamanaka, Naoki Koyama, Takao Asano.
  • Organizer: International Psychogeriatric Association (IPA) 2007 Osaka Silver Congress
  • Place of Presentation: Osaka, Japan
  • Year and Date: 2007-10-17