Induction of neuroprotective microenvironment and intervention of neurodegenerative condition by the intra-bone marrow bone-marrow transplantation

2011 Fiscal Year Final Research Report

• Project/Area Number: 21590458
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Experimental pathology
• Research Institution: Institute for Developmental Research, Aichi Human Service Center
• Principal Investigator: SHIMADA Atsuyoshi 愛知県心身障害者コロニー発達障害研究所, 病理学部, 室長 (50311444)
• Project Period (FY): 2009 – 2011
• Keywords: 骨髄移植 / 老化 / 神経変性

Research Abstract

We hypothesized that brain aging might be caused by a loss of neuroprotective function from brain immune cells. Mice with accelerated brain aging lacked the neuroprotective responses exerted by neuron-glia interaction after being challenged with brain tissue injury. When these diseased mice received bone marrow transplantation from normal mouse donors, donor-derived marrow cells entered the recipients' brains and differentiated into brain immune cells. These results indicate the possibility of preventing brain aging by bone marrow transplantation.

Research Products

• [Journal Article] 脳と免疫系の相互作用という観点から老化促進モデルマウスをとらえる (2012)
  • Author(s): 島田厚良、石井さなえ
  • Journal Title: 基礎老化研究 Volume: 36(1) Pages: 13-20
  • Peer Reviewed
• [Journal Article] Senescence-accelerated mice(SAMs) as a model for brain aging and immunosenescence (2011)
  • Author(s): Shimada, A. and Hasegawa-Ishii, S
  • Journal Title: Aging Dis Volume: 2 Pages: 414-436
  • URL: http://www.ncbi.nlm.nih.gov/pubmed?term=Senescence-accelerated%20mice%20(SAMs)%20as%20a%20model%20for%20brain%20aging%20and%20immunosenescence
  • Peer Reviewed
• [Journal Article] 免疫系と神経系の接点から老化促進モデルマウスをとらえる (2011)
  • Author(s): 島田厚良、石井さなえ
  • Journal Title: 日本老年医学会雑 Volume: 48(5) Pages: 439-446
• [Journal Article] Amelioration of 2, 4, 6-trinitrobenzene sulfonic acid-induced colitis in mice by immunoregulatory dendritic cells (2011)
  • Author(s): Hoshino, S., Kurishima, A., Inaba, M., Ando, Y., Fukui, T., Uchida, K., Nishio, A., Iwai, H., Yokoi, T. Ito, T., Hasegawa-Ishii, S., Shimada, A., Li, M., Okazaki, K., and Ikehara, S
  • Journal Title: J. Gastroenterol Volume: 46 Pages: 1368-1381
  • URL: http://www.ncbi.nlm.nih.gov/pubmed?term=Amelioration%20of%202%2C4%2C6-trinitrobenzene%20sulfonic%20acid-induced%20colitis%20in%20mice%20by%20immunoregulatory%20dendritic%20cells
  • Peer Reviewed
• [Journal Article] Proteomic identification of hippocampal proteins vulnerable to oxidative stress in excitotoxin-induced acute neuronal injury (2011)
  • Author(s): Furukawa, A., Kawamoto, Chiba, Y., Takei, S., Hasegawa-Ishii, S., Kawamura, N., Yoshikawa, K., Hosokawa, M., Oikawa, S., Kato, M., and Shimada, A.
  • Journal Title: Neurobiol. Dis Volume: 43 Pages: 706-714
  • URL: http://www.ncbi.nlm.nih.gov/pubmed?term=Proteomic%20identification%20of%20hippocampal%20proteins%20vulnerable%20to%20oxidative%20stress%20in%20excitotoxin-induced%20acute%20neuronal%20injury.%20
  • Peer Reviewed
• [Journal Article] Morphological impairments in microglia precede age-related neuronal degeneration in senescence-accelerated mice (2011)
  • Author(s): Hasegawa-Ishii, S., Takei, S., Chiba, Y., Furukawa, A., Umegaki, H., Iguchi, A., Kawamura, N., Yoshikawa, K., Hosokawa, M., and Shimada, A.
  • Journal Title: Neuropathology Volume: 31 Pages: 20-8
  • DOI: doi:10.1111/j.1440-1789.2010.01126.x
  • Peer Reviewed
• [Journal Article] Preferential localization of prostamide/prostaglandin F synthase in myelin sheaths of the central nervous system (2011)
  • Author(s): Yoshikawa, K., Takei, S., Hasegawa-Ishii, S., Chiba, Y., Furukawa, A., Kawamura, N., Hosokawa, M., Woodward, D. F., Watanabe, K., and Shimada, A.
  • Journal Title: Brain Res Volume: 1367 Pages: 22-32
  • URL: http://www.ncbi.nlm.nih.gov/pubmed?term=Preferential%20localization%20of%20prostamide%2Fprostaglandin%20F%20synthase%20in%20myelin%20sheaths%20of%20the%20central%20nervous%20system
  • Peer Reviewed
• [Journal Article] Defects in cytokine-mediated neuroprotective glial responses to excitotoxic hippocampal injury in senescence-accelerated mouse (2011)
  • Author(s): Hasegawa-Ishii, S., Takei, S., Inaba, M., Umegaki, H., Chiba, Y., Furukawa, A., Kawamura, N., Hosokawa, M., and Shimada, A.
  • Journal Title: Brain Behav. Immun Volume: 25 Pages: 83-100
  • URL: http://www.ncbi.nlm.nih.gov/pubmed?term=Defects%20in%20cytokine-mediated%20neuroprotective%20glial%20responses%20to%20excitotoxic%20hippocampal%20injury%20in%20senescence-accelerated%20mouse
  • Peer Reviewed
• [Journal Article] The eosin-shadow method : a selective enhancement of light microscopic visualization of pancreatic zymogen granules on hematoxylin-eosin sections (2010)
  • Author(s): Takei, S., Tokuhira, Y., Shimada, A., Hosokawa, M., and Fukuoka, S
  • Journal Title: Anat. Sci. Int Volume: 85 Pages: 245-250
  • URL: http://www.ncbi.nlm.nih.gov/pubmed?term=The%20eosin-shadow%20method%3A%20a%20selective%20enhancement%20of%20light%20microscopic%20visualization%20of%20pancreatic%20zymogen%20granules%20on%20hematoxylin-eosin%20sections
  • Peer Reviewed
• [Journal Article] Oxidatively generated DNA damage induced by 3-amino-5-mercapto-1, 2, 4-triazole, a metabolite of carcinogenic amitrole (2010)
  • Author(s): Furukawa, A., Oikawa, S., Harada, K., Sugiyama, H., Hiraku, Y., Murata, M., Shimada, A., and Kawanishi, S
  • Journal Title: Mut. Res. Fund. Mol. Mech. Mutag Volume: 694 Pages: 7-12
  • URL: http://www.ncbi.nlm.nih.gov/pubmed/?term=Oxidatively%20generated%20DNA%20damage%20induced%20by%203-amino-5-mercapto-1%2C2%2C4-triazole%2C%20a%20metabolite%20of%20carcinogenic%20amitrole
  • Peer Reviewed
• [Journal Article] Proteomic analysis of aging brain in SAMP10 mouse : a model of age-related cerebral degeneration (2010)
  • Author(s): Furukawa, A., Oikawa, S., Hasegawa-Ishii, S., Chiba, Y., Kawamura, N., Takei, S., Yoshikawa, K., Hosokawa, M., Kawanishi, S., and Shimada, A.
  • Journal Title: Mech. Ageing Dev Volume: 131 Pages: 379-388
  • URL: http://www.ncbi.nlm.nih.gov/pubmed?term=Proteomic%20analysis%20of%20aging%20brain%20in%20SAMP10%20mouse%3A%20a%20model%20of%20age-related%20cerebral%20degeneration
  • Peer Reviewed
• [Journal Article] c-Ret-mediated hearing loss in mice with Hirschsprung disease (2010)
  • Author(s): Ohgami, N., Ida-Eto, M., Shimotake, T., Sakashita, N., Sone, M., Nakashima, T., Tabuchi, K., Hoshino, T., Shimada, A., Tsuzuki, T., Yamamoto, M., Sobue, G., Jijiwa, M., Asai, N., Hara, A., Takahashi, M., Kato, M
  • Journal Title: Proc. Natl. Acad. Sci. U. S. A. Volume: 107 Pages: 13051-13056
  • URL: http://www.ncbi.nlm.nih.gov/pubmed/20616061
  • Peer Reviewed
• [Journal Article] Immunohistochemical localization of aggresomal proteins in glial cytoplasmic inclusions in multiple system atrophy
  • Author(s): Chiba, Y., Takei, S., Kawamura, N., Kawaguchi, Y., Sasaki, K., Hasegawa-Ishii, S., Furukawa, A., Hosokawa, M., and Shimada, A.
  • Journal Title: Neuropathol. Appl. Neurobiol Volume: (in press)
  • DOI: doi:10.1111/j.1365-2990.2011.01229.x
  • Peer Reviewed
• [Presentation] 免疫系と神経系の接点から老化促進モデルマウスをとらえる (2011)
  • Author(s): 島田厚良
  • Organizer: 日本基礎老化学会シンポジウム"日本の基礎老化研究の現状と展望"-日本基礎老化学会
  • Place of Presentation: 野田市
  • Year and Date: 2011-10-08
• [Presentation] Immunohistochemical demonstration of enhanced prostaglandin F_<2α> production following kainic acid-induced seizures in rat hippocampus (2011)
  • Author(s): Takei S, Hasegawa-Ishii S, Uekawa A, Furukawa A, Chiba Y, Kawamura N, Hosokawa M, Woodward DF, Watanabe K, Shimada A
  • Organizer: Bio Active Lipid Meeting
  • Place of Presentation: Seattle, USA
  • Year and Date: 2011-09-19
• [Presentation] SAMP10に見られるサイトカインを介した神経保護的グリア応答の低下 (2011)
  • Author(s): 石井さなえ、稲葉宗夫、武井史郎、河村則子、千葉陽一、細川昌則、島田厚良
  • Organizer: SAM研究協議会
  • Place of Presentation: 岐阜市
  • Year and Date: 2011-07-08
• [Presentation] Defects in cytokine-mediated neuroprotective glial responses to excitotoxic hippocampal injury in senescence-accelerated mouse (2011)
  • Author(s): Hasegawa-Ishii S, Takei S, Shimada A
  • Organizer: 18^<th> Annual Meeting of The PsychoNeuroImmunology Research Society
  • Place of Presentation: Chicago, USA
  • Year and Date: 2011-06-09
• [Presentation] カイニン酸誘導てんかん発作に伴う海馬プロスタグランジンF2α産生亢進の免疫組織学的解析 (2011)
  • Author(s): 武井史郎、石井さなえ、上川篤志、千葉陽一、河村則子、Woodward DF、渡部紀久子、島田厚良
  • Organizer: 日本神経病理学会
  • Place of Presentation: 京都市
  • Year and Date: 2011-06-04
• [Presentation] 老化促進モデルマウスに見られるサイトカインを介した神経保護的グリア応答機能の低下 (2011)
  • Author(s): 石井さなえ、武井史郎、稲葉宗夫、千葉陽一、古川絢子、河村則子、細川昌則、島田厚良
  • Organizer: 日本神経病理学会
  • Place of Presentation: 京都市
  • Year and Date: 2011-06-04
• [Presentation] The distribution of prostamide/prostaglandin F synthase in the developing and adult mouse central nervous system (2010)
  • Author(s): Shimada, A., Yoshikawa, K., Takei, S., Hasegawa-Ishii, S., Chiba, Y., Furukawa, A., Kawamura, N., Woodward, D. F., Watanabe, K
  • Organizer: 第83回日本生化学会大会
  • Place of Presentation: 神戸市
  • Year and Date: 2010-12-10
• [Presentation] Prostamide/prostaglandin F synthaseのマウス中枢神経系および培養オリゴデンドロサイトにおける分布 (2010)
  • Author(s): 千葉陽一、島田厚良、吉川圭介、武井史郎、石井さなえ、古川絢子、河村則子、David F Woodward、渡部紀久子
  • Organizer: 第33回日本神経科学大会
  • Place of Presentation: 神戸市
  • Year and Date: 2010-09-03
• [Presentation] 脳組織防御機構の破綻と加齢性神経変性 (2010)
  • Author(s): 島田厚良
  • Organizer: 日本基礎老化学会第33回大会,シンポジウム:老化と疾患
  • Place of Presentation: 名古屋市
  • Year and Date: 2010-06-18
• [Presentation] 加齢性神経変性におけるミクログリアの関与と骨髄内骨髄移植による実験的治療 (2010)
  • Author(s): 石井さなえ、稲葉宗夫、武井史郎、古川絢子、河村則子、千葉陽一、細川昌則、池原進、島田厚良
  • Organizer: 日本基礎老化学会第33回大会
  • Place of Presentation: 名古屋市
  • Year and Date: 2010-06-17
• [Presentation] A novel type of PGF synthase belonging to the thioredoxin-like superfamily (2010)
  • Author(s): Watanabe, K. and Shimada, A
  • Organizer: Keystone Symposium "Bioactive Lipids : Biochemistry and Diseases"
  • Place of Presentation: 京都市
  • Year and Date: 2010-06-07
• [Presentation] 興奮毒性による海馬損傷における酸化損傷タンパク質の生成 (2010)
  • Author(s): 古川絢子、島田厚良、河村則子、武井史郎、千葉陽一、石井さなえ、細川昌則
  • Organizer: 日本神経病理学会
  • Place of Presentation: 東京
  • Year and Date: 2010-04-23
• [Presentation] Glial cytoplasmic inclusionはaggresomeとしての性格を有する (2009)
  • Author(s): 千葉陽一、島田厚良、武井史郎、河村則子、石井さなえ、古川絢子、佐々木健介、岩城徹、細川昌則
  • Organizer: 第32回日本神経科学大会
  • Place of Presentation: 名古屋市
  • Year and Date: 2009-09-18
• [Presentation] 興奮毒性による海馬損傷における酸化損傷タンパク質の生成 (2009)
  • Author(s): 古川絢子、島田厚良、河村則子、武井史郎、千葉陽一、石井さなえ、細川昌則
  • Organizer: 第32回日本神経科学大会
  • Place of Presentation: 名古屋市
  • Year and Date: 2009-09-18
• [Presentation] 促進モデルマウスにみられるミクログリアの異常と神経変性 (2009)
  • Author(s): 島田厚良、石井さなえ、武井史郎、河村則子、古川絢子、千葉陽一、細川昌則
  • Organizer: 第32回日本神経科学大会
  • Place of Presentation: 名古屋市
  • Year and Date: 2009-09-16
• [Presentation] SAMP10への骨髄内骨髄移植によるミクログリア再生を介した神経変性の制御 (2009)
  • Author(s): 島田厚良、石井さなえ、稲葉宗夫、河村則子、武井史郎、古川絢子、千葉陽一、細川昌則、池原進
  • Organizer: 第24回老化促進モデルマウス研究協議会
  • Place of Presentation: 松本市
  • Year and Date: 2009-07-09
• [Presentation] SAMP10にみられるミクログリアの形態異常と興奮毒性に対する応答異常 (2009)
  • Author(s): 石井さなえ、島田厚良、千葉陽一、古川絢子、河村則子、武井史郎、細川昌則
  • Organizer: 第24回老化促進モデルマウス研究協議会
  • Place of Presentation: 松本市
  • Year and Date: 2009-07-09
• [Presentation] 加齢性神経変性疾患における封入体形成へのaggresomeの関与 (2009)
  • Author(s): 千葉陽一、島田厚良、武井史郎、河村則子、石井さなえ、古川絢子、細川昌則
  • Organizer: 日本基礎老化学会大会
  • Place of Presentation: 横浜市
  • Year and Date: 2009-06-20
• [Presentation] プロスタグランジン抑制による興奮毒性誘発神経細胞死の制御 (2009)
  • Author(s): 島田厚良、吉川圭介、北芳博、清水孝雄、石井さなえ、古川絢子、河村則子、千葉陽一
  • Organizer: 第50回日本神経病理学会総会
  • Place of Presentation: 高松市
  • Year and Date: 2009-06-06
• [Presentation] Glial cytoplasmic inclusionsはaggresomeとしての側面を有する (2009)
  • Author(s): 千葉陽一、島田厚良、武井史郎、河村則子、石井さなえ、古川絢子、佐々木健介、岩城徹、細川昌則
  • Organizer: 第50回日本神経病理学会総会
  • Place of Presentation: 高松市
  • Year and Date: 2009-06-05
• [Presentation] 老化促進モデルマウスにみられるミクログリアの形態異常と興奮毒性に対する応答異常 (2009)
  • Author(s): 石井さなえ、島田厚良、千葉陽一、古川絢子、河村則子、武井史郎、細川昌則
  • Organizer: 第50回日本神経病理学会総会
  • Place of Presentation: 高松市
  • Year and Date: 2009-06-05
• [Presentation] SAMP10の加齢性神経変性に伴うタンパク質発現変化に関するプロテオミクス解析 (2009)
  • Author(s): 古川絢子、島田厚良、及川伸二、千葉陽一、石井さなえ、河村則子、武井史郎、細川昌則
  • Organizer: 第50回日本神経病理学会総会
  • Place of Presentation: 高松市
  • Year and Date: 2009-06-05
• [Presentation] The distribution of prostamide/prostaglandin F synthase in mouse brain : Developmental changes and localization to the myelin sheath (2009)
  • Author(s): Shimada, A
  • Organizer: 4th International Conference on Phospholipase A_2 and Lipid Mediators Poster Workshop I
  • Place of Presentation: 東京
  • Year and Date: 2009-05-26
• [Book] Clinical Pathological Conference(C. P. C.)学業の遅れと歩行の異常で発症し、多彩な神経症状が進行した男子症例.「小児神経学の進歩-第39集」(日本小児神経学会教育委員会編) (2010)
  • Author(s): 林雅晴、小森拓、島田厚良
  • Total Pages: 129-144
  • Publisher: 診断と治療社
• [Book] The SAM strain of mice, a higher oxidative stress, age-dependent degenerative disease, and senescence acceleration model. In : Aging and Age-related Disorders, Oxidative Stress in Applied Basic Research and Clinical Practice 3(Bondy, S. C. and Maiese, K. eds.) (2010)
  • Author(s): Chiba, Y., Shimada, A., and Hosokawa, M
  • Total Pages: 359-380
  • Publisher: Humana Press, New York
• [Book] SAMP10 strain as a model for the study of brain aging, in T. Takeda, ed. The senescence-accelerated mouse(SAM): Achievements and Future Directions
  • Author(s): A. Shimada, A., Hasegawa-Ishii, S., and Furukawa, A
  • Publisher: Elsevier, Amsterdam(in press)