Regulation of brain aging by renewal of microglia and recruitment of neural stem cell by intra-bone marrow-bone marrow transplantation

• Project/Area Number: 22790392
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Experimental pathology
• Research Institution: Institute for Developmental Research, Aichi Human Service Center
• Principal Investigator: ISHII Sanae (ISHII HASEGAWA Sanae) 愛知県心身障害者コロニー発達障害研究所, 病理学部, リサーチレジデント (40435863)
• Project Period (FY): 2010 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2011: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000); Fiscal Year 2010: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 骨髄内移植 / ミクログリア / 脳老化病態 / 骨髄内骨髄移植 / 骨髄由来細胞 / 脈絡叢 / SAMP10マウス

Research Abstract

After syngeneic intra-bone marrow-bone marrow transplantation(IBM-BMT), marrow-derived cells rapidly appeared in the leptomeninges, choroid plexus, perivascular regions and circumventricular organs, which lack the blood-brain barrier(BBB). Marrow-derived cells entered several small discrete regions of the brain parenchyma, although they did not enter the remaining major part. Marrow-derived cells exhibited ramified morphology and expressed Iba-1 but not GFAP, CNPase or NeuN, indicative of the myeloid lineage. In chimeras in which SAMP10 mice were recipients, a larger number of donor-derived cells entered more regions than in chimeras in which B6 mice were recipients. After allogeneic IBM-BMT, the learning ability of old SAMP10 mice was not ameliorated, which may be due to the failure in the recovery of peripheral T cells after IBM-BMT.

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
  • NAID: 10030253433
  • Peer Reviewed
• [Journal Article] Immunohistochemical localization of aggresomal proteins in glial cytoplasmic inclusions in multiple system atrophy. (2012)
  • Author(s): Chiba Y., Takei S., Kawamura N., Kawaguchi Y., Sasaki K., Hasegawa-Ishii S., Furukawa A., Hosokawa M., Shimada A.
  • Journal Title: Neuropathol. Appl. Neurobiol. Volume: 38(6) Issue: 6 Pages: 559-71
  • DOI: 10.1111/j.1365-2990.2011.01229.x
  • 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(1) 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] 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 Issue: 1 Pages: 20-8
  • DOI: 10.1111/j.1440-1789.2010.01126.x
  • 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(5) Pages: 414-435
  • 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: 日本老年医学会雑誌 Volume: 48(5) Pages: 439-446
  • NAID: 10031130846
  • Peer Reviewed
• [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., M. Li, K. Okazaki, S. Ikehara
  • Journal Title: J. Gastroenterol Volume: 46(12) 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] 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] Proteomic identification of hippocampal proteins vulnerable to oxidative stress in excitotoxin-induced acute neuronal injury (2011)
  • Author(s): Furukawa A., Kawamoto Y., 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(3) 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] 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., M.Li, K.Okazaki, S.Ikehara
  • Journal Title: J.Gastroenterol. Volume: 46(12) Pages: 1368-1381
  • 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 Y., Chiba Y., Takei S., Hasegawa-Ishii S., Kawamura N., Yoshikawa K., Hosokawa M., Oikawa S., Kato M., Shimada A.
  • Journal Title: Neurobiol.Dis. Volume: 43(3) Pages: 706-714
  • Peer Reviewed
• [Journal Article] Senescence-accelerated mice (SAMs) as a model for brain aging and immunosenescence (2011)
  • Author(s): Shimada A., Hasegawa-Ishii S.
  • Journal Title: Aging Dis. Volume: 2(5) Pages: 414-435
  • 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., Shimada, A.
  • Journal Title: Brain Behav.Immun. Volume: 25(1) Pages: 83-100
  • 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., Shimada, A.
  • Journal Title: Neuropathology Volume: 31 Pages: 20-28
  • 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., Shimada, A.
  • Journal Title: Brain Res. Volume: 1367 Pages: 22-32
  • Peer Reviewed
• [Journal Article] Defects in cytokine-mediated neuroprotective glial responses to excitotoxic hippocampal injury in senescence-accelerated mouse. (2011)
  • Author(s): Hasegawa-lshii, S., Takei, S., lnaba, M., Umegaki, H., Chiba, Y., Furukawa, A., Kawamura, N., Hosokawa, M., and Shimada, A.
  • Journal Title: Brain Behav. lmmun. Volume: 25 Issue: 1 Pages: 83-100
  • 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 Y., Chiba Y., Takei S., Hasegawa-lshii S., Kawamura N., Yoshikawa K., Hosokawa M., Oikawa S., Kato M., and Shimada A.
  • Journal Title: Neurobiol. Dis. Volume: 43 Issue: 3 Pages: 706-714
  • Peer Reviewed
• [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., lwai H., Yokoi T., lto T., Hasegawa-lshii S., Shimada A., M. Li, K. Okazaki, S. lkehara.
  • Journal Title: J. Gastroenterol. Volume: 46 Issue: 12 Pages: 1368-1381
  • Peer Reviewed
• [Journal Article] lmmunohistochemical localization of aggresomal proteins in glial cytoplasmic inclusions in multiple system atrophy. (2011)
  • Author(s): Chiba Y., Takei S., Kawamura N., Kawaguchi Y., Sasaki K., Hasegawa-lshii S., Furukawa A., Hosokawa M., Shimada A.
  • Journal Title: Neuropathol. Appl. Neurobiol.
  • Peer Reviewed
• [Journal Article] Senescence-accelerated mice (SAMs) as a model for brain aging and immunosenescence. (2011)
  • Author(s): Shimada A. and Hasegawa-lshii S.
  • Journal Title: Aging Dis.
  • 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] 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., Shimada, A.
  • Journal Title: Mech.Ageing Dev. Volume: 131 Pages: 379-388
  • 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-lshii, 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
  • Peer Reviewed
• [Presentation] Immunohistochemical demonstration of enhanced prostaglandin F2 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
  • Year and Date: 2011-09-19
• [Presentation] Immunohistochemical demonstration of enhanced prostagiandin 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
  • Year and Date: 2011-09-19
• [Presentation] lmmunohistochemical demonstration of enhanced prostaglandin F_<2α> production following kainic acid-induced seizures in rat hippocampus. (2011)
  • Author(s): Takei S., Hasegawa-kshii S., Uekawa A., Furukawa A., Furukawa A., Chiba Y., Kawamura N., Hosokawa M., Woodward DF., Watanabe K., Shimada A.
  • Organizer: Bio Active Lipid Meeting
  • Place of Presentation: Seattle
  • Year and Date: 2011-09-19
• [Presentation] 学習の遅れと歩行障害で発症し、多彩な神経症状が進行した男性の剖検例 (2011)
  • Author(s): 千葉陽一,武井史郎,石井さなえ,細川昌則,島田厚良、小森拓
  • Organizer: 第3回日本神経病理学会東海・北陸地方会
  • Place of Presentation: 愛知
  • Year and Date: 2011-09-10
• [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
  • 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: 18th Annual Meeting of The PsychoNeuroImmunology Research Society
  • Place of Presentation: Chicago
  • Year and Date: 2011-06-09
• [Presentation] Defects in cytokine-mediated neuroprotective glial responses to excitotoxic hippocampal iniuty in senescence-accelerated mouse (2011)
  • Author(s): Hasegawa-Ishii S., Takei S., Shimada A.
  • Organizer: 18^<th> Annual Meeting of The PsychoNeurolmmunology Research Society
  • Place of Presentation: Chicago
  • Year and Date: 2011-06-09
• [Presentation] Defects in cytokine-mediated neuroprotective glial responses to excitotoxic hippocampal injury in senescence-accelerated mouse. (2011)
  • Author(s): Hasegawa-lshii S., Takei S., Shimada A.
  • Organizer: 18^<th>Annual Meeting of The PsychoNeurolm munology Research Society
  • Place of Presentation: Chicago
  • Year and Date: 2011-06-09
• [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
  • Year and Date: 2011-06-04
• [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F_<2α>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
  • Year and Date: 2011-06-04
• [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F2a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
  • 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): Atsuyoshi Shimada, Keisuke Yoshikawa, Shiro Takei, Sanae Hasegawa-Ishii, Yoichi Chiba, Ayako Furukawa, Noriko Kawamura, David F. Woodward, and Kikuko Watanabe
  • Organizer: 第83回日本生化学会大会
  • Place of Presentation: 神戸
  • 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] Microglia as a potential target for age-related neurodegeneration in SAMP10 mice (2010)
  • Author(s): Ishii S, Inaba M, Takei S, Furukawa A, Chiba Y, Kawamura N, Hosokawa M, Ikehara S, Shimada A.
  • Organizer: 第33回日本基礎老化学会
  • Place of Presentation: 名古屋
  • Year and Date: 2010-06-17
• [Presentation] The distribution of prostamide/prostaglandin F synthase in the developing and adult mouse central nervous system (2010)
  • Author(s): Atsuyoshi Shimada, Keisuke Yoshikawa, Shiro Takei, Sanae Hasegawa-Ishii, Yoichi Chiba, Ayako Furukawa, Noriko Kawamura, David F. Woodward, and Kikuko Watanabe
  • Organizer: Keystone symposia
  • Place of Presentation: 京都
  • Year and Date: 2010-06-09
• [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: 第51回日本神経病理学会総会学術研究会
  • Place of Presentation: 東京
  • Year and Date: 2010-04-23
• [Book] The senescence-accelerated mouse(SAM): Achievements and Future Directions (2011)
  • Author(s): Shimada A, Hasegawa-Ishii S, Furukawa A
  • Publisher: Elsevier
• [Book] The senescence-accelerated mouse (SAM) : Achievements and Future Directions. (Toshio Takeda, ed.) (2011)
  • Author(s): Shimada A, Haseaawa-Ishii S, Furukawa A(2011)
  • Publisher: Elsevier
• [Book] The senescence-accelerated mouse (SAM) : Achievements and Future Directions. (Toshio Takeda, ed.) (2011)
  • Author(s): Shimada A, Hasegawa-lshii S, Furukawa A
  • Publisher: Elsevier