Neuropathological study of microglia in autopsied brains and transgenic model dementia disorders

• Project/Area Number: 18500276
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Nerve anatomy/Neuropathology
• Research Institution: Gunma University
• Principal Investigator: SASAKI Atsushi Gunma University, 大学院・医学系研究科, 准教授 (80225862)
• Co-Investigator(Kenkyū-buntansha): SHOJI Mikio 弘前大学, 医学部, 教授 (60171021) ; IKEDA Masaki 群馬大学, 医学部, 講師 (50222899)
• Project Period (FY): 2006 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥4,070,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥570,000); Fiscal Year 2008: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2007: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2006: ¥1,600,000 (Direct Cost: ¥1,600,000)
• Keywords: ミクログリア / 神経病理学 / 認知症 / トランスジェニックマウス / アルツハイマー病 / タウオパチー / 脳腫瘍 / microglia / amyloid β protein / tau / alpha-synuclein / transgenic mice / tauopathy / culture / MHC class II / Alzheimer's disease / astrocytoma / lymphoma / Ibal / AT8

Research Abstract

我々はヒト認知症剖検脳とアミロイドβ蛋白(A・)ないしリン酸化tauのtransgenic(TG)miceを主な研究対象として、ミクログリアの変化を病理学的に検索し、その機能・役割を検討した。その結果、ミクログリアはA・とリン酸化tauの沈着と相関して活性化され、その活性化はA・沈着後に明瞭となり、その処理・清掃に関与する生体防御機能が示唆された。さらに、活性化は、モデルマウス脳よりもヒト認知症脳でより強く、今後の実験解析で注意する必要性が示された。

Research Products

• [Journal Article] Motor impairment ameliorated by L-DOPA administration in human alpha-synuclein A30P+A53T transgenic mice with alpha-synuclein pathology (2009)
  • Author(s): Ikeda M, Sasaki A, Shoji M, 他14名
  • Journal Title: Brain Research 1250巻 Pages: 232-241
  • Peer Reviewed
• [Journal Article] Motor impairment ameliorated by L-DOPA administration in human alpha-synuclein. A30P+A53T transgenic mice with alpha-synuclein pathology. (2009)
  • Author(s): Ikeda M, Kawarabayashi T, Harigaya Y, Sasaki A et al.
  • Journal Title: Brain Research 1250 Pages: 232-241
  • Peer Reviewed
• [Journal Article] Microglial activation in brain lesions with tau deposits : comparison of human tauopathies and tau transgenic mice TgTauP301L (2008)
  • Author(s): Sasaki A, Ikeda M, Shoji M, 他7名
  • Journal Title: Brain Research 1214巻 Pages: 159-168
  • Peer Reviewed
• [Journal Article] Diversity of glial cell components in pilocytic astrocytoma (2008)
  • Author(s): Tanaka Y, Sasaki A, 他2名
  • Journal Title: Neuropathology 28巻 Pages: 399-407
  • NAID: 10026608458
  • Peer Reviewed
• [Journal Article] Enhanced accumulation of phosphorylated alpha-synuclein in double transgenic mice expressing mutant beta-amyloid precursor protein and presenilin-1 (2008)
  • Author(s): Kurata T, Ikeda M, Shoji M, 他13名
  • Journal Title: Journal of Neuroscience Research 85巻 Pages: 2246-2252
  • Peer Reviewed
• [Journal Article] Microglial activation in brain lesions with tau deposits: comparison of human tauopathies and tau transgenic mice Yg Tau1301L. (2008)
  • Author(s): Sasaki A, Kawarabayashi T, Murakami T et al.
  • Journal Title: Brain Research 1214 Pages: 159-168
  • Peer Reviewed
• [Journal Article] Microglial activation state in Tg2576 transgenic mice (2008)
  • Author(s): Sasaki A, Shoji M, et. al.
  • Journal Title: Neuropathology 27 Pages: 205-205
• [Journal Article] Enhanced accumulation of phosphorylated alpha-synuclein in double transgenic mice expressing mutant beta-amyloid precursor protein and presenilin-1 (2008)
  • Author(s): Kurata T, Ikeda M. M, Shoji M, et. al.
  • Journal Title: Journal of Neuroscience Research 85 Pages: 2246-2252
  • Peer Reviewed
• [Journal Article] 病理診断に役立つグリア細胞のマーカー (2007)
  • Author(s): 佐々木惇
  • Journal Title: 病理と臨床 25巻 Pages: 1014-1020
• [Journal Article] 病理診断に役立つグリア細胞のマーカー (2007)
  • Author(s): 佐々木 惇
  • Journal Title: 病理と臨床 25 Pages: 1014-1020
• [Journal Article] Type-specific evolution of amyloid plaque and angiopathy in APPsw mice (2006)
  • Author(s): Harigaya Y, Ikeda M, Sasaki A, Shoji M, 他6名
  • Journal Title: Neuroscience Letter 395巻 Pages: 37-41
  • Peer Reviewed
• [Journal Article] Enhanced accumulation of tau in doubly transgenic mice expressing mutant ・APP and presenilin-1 (2006)
  • Author(s): Samura E, Shoi M, Sasaki A, Ikeda M, 他11名
  • Journal Title: Brain Research 1094巻 Pages: 192-199
  • Peer Reviewed
• [Journal Article] Chemokine expression by astrocytes plays a role in microglia/macrophage activation and subsequent neurodegeneration in secondary progressive multiple sclerosis (2006)
  • Author(s): Tanuma N, Sakuma H, Sasaki A, 他1名
  • Journal Title: Acta Neuropathologica 112巻 Pages: 195-204
  • Peer Reviewed
• [Journal Article] Cortical neuronal and glial pathology in TgTauP301L transgenic mice : Neuronal degeneration, memory disturbance, and phenotypic variation (2006)
  • Author(s): Murakami T, Ikeda M, Sasaki A, Shoji M, 他22名
  • Journal Title: American Journal of Pathology 169巻 Pages: 1365-1376
  • Peer Reviewed
• [Journal Article] Microglial response in alpha-synucleinopathies (2006)
  • Author(s): Sasaki A, Shoji M, Ikeda M, 他3名
  • Journal Title: Neuropathology(proceedings) 26巻
• [Journal Article] Microglial activation in human tauopathies and transgenic mice models. (2006)
  • Author(s): Sasaki A., Shoji M., Kawarabayashi T et al.
  • Journal Title: XVIth international Congress of Neuropathology (abstract) Pages: 179-179
• [Journal Article] Microglial response in a-synucleionopathies. (2006)
  • Author(s): Sasaki A., Shoji M., Kawarabayashi T.et al.
  • Journal Title: Neuropathology (Proceedings of the 47th Annual Meeting of the Japanese Society of Neuropathology) 26・2
• [Journal Article] Chemokine expression by astrocytes plays a role in microglia/macrophage activation and subsequent neurodegeneration in secondary progressive multiple sclerosis. (2006)
  • Author(s): Tanuma N, Matsumoto Y, Sasaki A.
  • Journal Title: Acta Neuropathol 112・2 Pages: 195-204
• [Journal Article] Cortical neuronal and glial pathology in TgTau^<P301L> transgenic mice : Neuronal degeneration, memory disturbance, and phenotypic variation. (2006)
  • Author(s): Murakami E, Ikeda M, Sasaki A, Shoji M et al.
  • Journal Title: Am J Pathol 169・4 Pages: 1365-1376
• [Journal Article] Molecular mechanisms of ischemic neuronal cell death-with relevance to Alzheimer' s disease. (2006)
  • Author(s): Hayashi T., Shoji M., Abe K.
  • Journal Title: Curr Alzheimer Res 3・4 Pages: 351-358
• [Journal Article] Dynamin-binding protein gene on chromosome 10q is associated with late-onset Alzheimer' s disease. (2006)
  • Author(s): Kuwano R, Mitasnila A., Shoji M. et al.
  • Journal Title: Hum Mol Genet 15・13 Pages: 2170-2182
• [Presentation] Microglial density in astrocytic and oligodendroglial tumours (2008)
  • Author(s): Yu K, Sasaki Aら
  • Organizer: Annual meeting of the British Neuro-oncology society
  • Place of Presentation: Preston, UK
  • Year and Date: 2008-06-25
• [Presentation] Morphological and functional analysis of radiofrequency field-exposed microglial cells in vitro (2008)
  • Author(s): Sekijima M, Sasaki Aら
  • Organizer: BEMS 30^<th> annual meeting
  • Place of Presentation: San Diego
  • Year and Date: 2008-06-08
• [Presentation] Morphological and functional analysis of radiofrequency field- exposed microglial cells in vitro. (2008)
  • Author(s): Sekijima M, Hirose H, Kaji N, Nojima T, Sasaki A et al.
  • Organizer: BEMS 30th annual meeting
  • Place of Presentation: San Diego (USA)
  • Year and Date: 2008-06-08
• [Presentation] アミロイドβ蛋白、リン酸化タウ沈着とミクログリア活性化 : トランスジェニックマウスを用いた病理学的検討 (2008)
  • Author(s): 佐々木惇
  • Organizer: 第97回日本病理学会総会
  • Place of Presentation: 金沢
  • Year and Date: 2008-05-16
• [Presentation] アミロイドβ淡白、リン酸化タウ沈着とミクログツア活性化:トランスジェニックマウスを用いた病理学的検討。 (2008)
  • Author(s): 佐々木惇、大石琢磨ら
  • Organizer: 弟97回日本病理学会総会
  • Place of Presentation: 金沢
  • Year and Date: 2008-05-16
• [Presentation] Analysis of phosphorylation of tau in transgenic mice overexpressing GSK-3b (2007)
  • Author(s): Ikeda M, Sasaki A, Shoji Mら
  • Organizer: Neuroscience 2007
  • Place of Presentation: San Diego
  • Year and Date: 2007-11-17
• [Presentation] Analysis of transgenic mice overexpressing mutant tau and GSK-3b (2007)
  • Author(s): Ikeda M, Sasaki A, Shoji Mら
  • Organizer: 第26回日本認知症学会
  • Place of Presentation: 大阪
  • Year and Date: 2007-10-15
• [Presentation] Tg2576トランスジェニックマウスにおけるミクログリア活性化状態について (2007)
  • Author(s): 佐々木惇、東海林幹夫、池田将樹ら
  • Organizer: 第48回日本神経病理学会
  • Place of Presentation: 東京
  • Year and Date: 2007-06-01
• [Presentation] 脳原発悪性リンパ腫におけるミクログリアマーカーの発現 : 解析と意義について (2007)
  • Author(s): 佐々木惇ら
  • Organizer: 第25回日本脳腫瘍病理学会
  • Place of Presentation: 熊本
  • Year and Date: 2007-04-20
• [Presentation] 脳原発悪性リンパ腫におけるミクログリアマーカーの発現:解析と意義について (2007)
  • Author(s): 佐々木 惇, 横尾 英明, ら
  • Organizer: 第25回日本脳腫瘍病理学会
  • Place of Presentation: 熊本
  • Year and Date: 2007-04-20
• [Presentation] Microglial activation in human tauopathies and transgenic mice models (2006)
  • Author(s): Sasaki A, Shoji M, Ikeda Mら
  • Organizer: 16^<th> International Congress of Neuropathology
  • Place of Presentation: San Francisco
  • Year and Date: 2006-09-12
• [Presentation] αシヌクレイノパチーにおけるミクログリアの病態について (2006)
  • Author(s): 佐々木惇、東海林幹夫、池田将樹
  • Organizer: 第47回日本神経病理学会
  • Place of Presentation: 岡山
  • Year and Date: 2006-05-24
• [Presentation] Pilocytic astrocytomaを構成する細胞の多様性について (2006)
  • Author(s): 田中優子、佐々木惇
  • Organizer: 第47回日本神経病理学会
  • Place of Presentation: 岡山
  • Year and Date: 2006-05-24
• [Book] EBM 精神科疾患の治療 (2006)
  • Author(s): 東海林 幹夫
  • Total Pages: 6
  • Publisher: 中外医学社
• [Patent(Industrial Property Rights)] パーキンソン病モデルtランスジェ ニックマウス (2008)
  • Inventor(s): 池田将樹, 山田秀一, 東海林幹夫
  • Industrial Property Rights Holder: 池田将樹, 山田秀一, 東海林幹夫
  • Filing Date: 2008-08-20