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Research on the fundamental molecules in relation to controlling brain aging : From neuronal cytoskeleton regulation to neuronal longevity control

Research Project

Project/Area Number 19300130
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Neurochemistry/Neuropharmacology
Research InstitutionNagasaki University

Principal Investigator

MORI Nozomu  Nagasaki University, 医歯薬学総合研究科, 教授 (00130394)

Co-Investigator(Kenkyū-buntansha) SIBAZAKI Masahiko  長崎大学, 医歯薬学総合研究科, 助教 (20445109)
森井 博吏  長崎大学, 大学院・医歯薬学総合研究科, 助教 (00345795)
Co-Investigator(Renkei-kenkyūsha) KAKIZAWA Sho  長崎大学, 医歯薬学総合研究科, 講師 (40291059)
YAMAGUCHI Yoko  長崎大学, 先導生命研究センター, 研究支援推進員 (50311345)
Project Period (FY) 2007 – 2009
Project Status Completed (Fiscal Year 2009)
Budget Amount *help
¥18,980,000 (Direct Cost: ¥14,600,000、Indirect Cost: ¥4,380,000)
Fiscal Year 2009: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2008: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2007: ¥8,060,000 (Direct Cost: ¥6,200,000、Indirect Cost: ¥1,860,000)
Keywords神経可塑性 / シグナル伝達 / 神経変性 / アクチン / 微小管 / 老化 / ニューロン / リン酸化 / ヒストン脱アセチル化酵素 / 可塑性 / スパイン / アクチン骨格 / HOAC / Shc / 海馬
Research Abstract

While I previously established N-Shc gene deficient mouse, the so-called KO mouse, we now made N-Shc and Grit/RICS double KO mouse. In norder to understand molecular mechanisms of actin dynamics regulation via N-Shc, we examined the role of Homer/Cupidin, an anchoring molecule to actins at neuronal synapses. We also analyzed the transcriptional regulatory mechanisms of BDNF promoter by NRSF/REST. In aged brains, it has been well known that various functions, particularly in hippocampus and cerebram, do decrease, but little is known about the cerebellar function. We, therefore, asked whether synaptic LTP in cerebellum changes or not in aging, and found that it indeed declined with age. We further found that the reduction of LTP is strongly affected by oxidative stress. Since the LTP at parallel fiber-Purkinje cell synapse depend on NO (nitric oxide), we assumed and finally demonstrated that this NO-dependent LTP is impaired by oxidative stress during aging. We also analyzed the effects of HDAC6 and SIRT2 in the protein aggregate turnover in neurons, and found that HDAC6 stimulated poly glutamin-mdiated protain aggregation in neuronal cells, which may be relevant to the studies of age-related neurodegenerative diseases. Finally, we established Asian research consortium on aging.

Report

(4 results)
  • 2009 Annual Research Report   Final Research Report ( PDF )
  • 2008 Annual Research Report
  • 2007 Annual Research Report
  • Research Products

    (52 results)

All 2010 2009 2008 2007 Other

All Journal Article (23 results) (of which Peer Reviewed: 9 results) Presentation (26 results) Book (2 results) Remarks (1 results)

  • [Journal Article] Protein oxidation inhibits NO-mediated signaling pathway for synaptic plasticity2010

    • Author(s)
      Kakizawa S, Shibazaki M, Mori N
    • Journal Title

      Neurobiol. Aging (in press)

    • NAID

      120006984470

    • Related Report
      2009 Final Research Report
  • [Journal Article] Interaction of Cupidin/Homer2 with two actin cytoskeletal regulators, Cdc42 small GTPase and Drebrin, in dendritic spines.2009

    • Author(s)
      Shiraishi-Yamaguchi Y, Sato Y, Sakai R, Mizutani A, Knopfel T, Mori N, Mikoshiba K, Furuichi T.
    • Journal Title

      BMC Neurosci. 10

    • NAID

      120006984146

    • Related Report
      2009 Final Research Report
  • [Journal Article] Japan-Korea Joint Seminar: Asian Aging Core for Longevity 2008 in Nagasaki---Toward the establishment of an asian aging research and education center.2009

    • Author(s)
      Shimokawa I, Park SC, Mori N, Hwang ES
    • Journal Title

      Mech. Ageing Dev. 130

      Pages: 198-201

    • Related Report
      2009 Final Research Report
  • [Journal Article] Remote control of activity-dependent BDNF gene promoter-I transcription mediated by REST/NRSF.2009

    • Author(s)
      Hara D, Fukuchi M, Miyashita T, Tabuchi A, Takasaki I, Naruse Y, Mori N, Kondo T, Tsuda M
    • Journal Title

      Biochem. Biophys. Res. Comm. 384

      Pages: 506-511

    • Related Report
      2009 Final Research Report
  • [Journal Article] 未病からの老化制御:生理的老化と病的老化の狭間にみる食養と抗加齢サプリ2009

    • Author(s)
      森望
    • Journal Title

      未病と抗老化 18

      Pages: 19-23

    • NAID

      40016672484

    • Related Report
      2009 Final Research Report
  • [Journal Article] Interaction of Cupidin/Homer2 with two actin cytoskeletal regulators, Cdc42 small GTPase and Drebrin, in dendritic spines.2009

    • Author(s)
      Shiraishi-Yamaguchi
    • Journal Title

      BMC Neuroscience 10

      Pages: 25-25

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Remote control of activity-dependent BDNF gene promoter-I transcription mediated by REST/NRSF.2009

    • Author(s)
      Hara D
    • Journal Title

      Biochemical and Biophysical Research Communications 384

      Pages: 506-511

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Japan-Korea Joint Seminar : Asian Aging Core for Longevity 2008 in Nagasaki-Toward the establishment of an Asian Aging Research and Education Center-September 4th to 6th, 2008 at Huis Ten Bosch, Nagasaki, Japan.2009

    • Author(s)
      Shimokawa I
    • Journal Title

      Mechanisms of Ageing and Development 130

      Pages: 198-201

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Evodiamine improves diet-induced obesity in a UCP1-independent manner: Involvement of anti-adipogenic mechanism and ERK/MAPK signaling.2008

    • Author(s)
      Wang T, Wang Y, Kontani Y, Kobayashi Y, Sato Y, Mori N, Yamashita H.
    • Journal Title

      Endocrinology 49

      Pages: 358-366

    • Related Report
      2009 Final Research Report
  • [Journal Article] Impaired basal thermal homeostasis in rats lacking capsaicin-sensitive peripheral small sensory neurons.2008

    • Author(s)
      Yamashita H, Wang Y, Kimura K, Inokuma K, Saito M, Kontani Y, Kobayashi Y, Mori N
    • Journal Title

      J. Biochem. 143

      Pages: 385-393

    • NAID

      10024908878

    • Related Report
      2009 Final Research Report
  • [Journal Article] Regulatory effects of Shc-related phosphotyrosine adaptor proteins on aging2008

    • Author(s)
      Zhang P, Ikejima T, Mori N
    • Journal Title

      Acta Pharmaceutica Sinica 43(8)

      Pages: 793-800

    • Related Report
      2009 Final Research Report
  • [Journal Article] 分子遺伝学の巨匠Seymour Benzer-Methuselahの夢と足跡2008

    • Author(s)
      森望
    • Journal Title

      実験医学 26(5月号)

      Pages: 1271-1276

    • Related Report
      2009 Final Research Report
  • [Journal Article] 晩年のBenzer研究室の動向からみるショウジョウバエの分子2008

    • Author(s)
      森望
    • Journal Title

      老年遺伝学基礎老化研究 32(3)

      Pages: 1-5

    • Related Report
      2009 Final Research Report
  • [Journal Article] Evodiamine improves diet-induced obesity in a UCP1-independent manner : Involvement of anti-adipogenic mechanism and ERK/MAPK signaling.2008

    • Author(s)
      Wang T
    • Journal Title

      Endocrinology 49

      Pages: 358-366

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Impaired basal thermal homeostasis in rats lacking capsaicin-sensitive peripheral small sensory neurons.2008

    • Author(s)
      Yamashita H
    • Journal Title

      J. Biochem. 143

      Pages: 385-393

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Regulatory effects of Shc-related phosphotyrosine adaptor proteins on aging. (in Chinese)2008

    • Author(s)
      Zhang P
    • Journal Title

      Acta Pharmaceutica Sinica 43(8)

      Pages: 793-800

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 晩年のBenzer研究室の動向からみるショウジョウバエの分子老年遺伝学2008

    • Author(s)
      森 望
    • Journal Title

      基礎老化研究 32(3)

      Pages: 1-5

    • NAID

      10024377714

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] PREGS induces long-term potentiation in the hippocampal dentate gyms of adult rats via tyrosine phosphorylation of NR2B coupled to ERK/CREB signaling.2007

    • Author(s)
      Chen L, Miyamoto Y, Furuya K, Mori N, Sokabe M.
    • Journal Title

      J. Neurophysiol. 98

      Pages: 1538-1548

    • Related Report
      2009 Final Research Report
  • [Journal Article] 老化・神経変性における神経系の再生・分化のメカニズムCognition and Dementia特集2007

    • Author(s)
      森望、大神和子
    • Journal Title

      神経変性疾患の神経再生・神経移植 6(1)

      Pages: 9-17

    • Related Report
      2009 Final Research Report
  • [Journal Article] 神経の可塑性が脳を守る:脳の抗加齢は可能だアンチ・エイジング医学-2007

    • Author(s)
      森望
    • Journal Title

      日本抗加齢医学会雑誌 2(2)

      Pages: 194-198

    • Related Report
      2009 Final Research Report
  • [Journal Article] 寿命の進化史と遺伝子エコソフィア特集2007

    • Author(s)
      森望
    • Journal Title

      Agingの博物自然史 19

      Pages: 17-24

    • Related Report
      2009 Final Research Report
  • [Journal Article] Large Na(+)influx and high Na(+),K(+)-ATPase activity in mitochondria-rich epithelial cells of the inner ear endolymphatic sac2007

    • Author(s)
      Miyashita T
    • Journal Title

      Pflugers Arch 453

      Pages: 905-913

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] PREGS induces LTP in the hippocampal dentate gyros of adult rats via the tyrosine phosphorylation of NR2B coupled to ERK/CREB [corrected] signaling2007

    • Author(s)
      Chen L
    • Journal Title

      J Neurophysiol 98

      Pages: 1538-1548

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Presentation] a molecular correlate of age-related cognitive decline and spine morphogenesis2009

    • Author(s)
      森望、Neuronal Shc
    • Organizer
      第2回ハーリム-長崎合同シンポジウム
    • Place of Presentation
      ハーリム大学(韓国・ソウル)
    • Year and Date
      2009-02-09
    • Related Report
      2009 Final Research Report
  • [Presentation] Neuronal She : a molecular correlate of age-related cognitive decline and spine morphogenesis2009

    • Author(s)
      森 望
    • Organizer
      第2回ハーリムー長崎合同シンポジウム
    • Place of Presentation
      韓国 パージム大学
    • Year and Date
      2009-02-09
    • Related Report
      2008 Annual Research Report
  • [Presentation] a molecular correlate of age-related cognitive decline and spine morphogenesis2009

    • Author(s)
      森望、Neuronal Shc
    • Organizer
      Symposium on Biological Complexity: Processes of Aging
    • Place of Presentation
      ソーク研究所(アメリカ・サンディエゴ)
    • Related Report
      2009 Final Research Report
  • [Presentation] Tubulin deacetylases in neuronal aging in vitro and in vivo2009

    • Author(s)
      森望
    • Organizer
      IAGG World Congress第19回国際老年学会
    • Place of Presentation
      パリ国際会議場(フランス・パリ)
    • Related Report
      2009 Final Research Report
  • [Presentation] Tubulin deacetylases in neuronal aging in vitro and in vivo2009

    • Author(s)
      森望
    • Organizer
      IAGG World Congress第19回 国際老年学会
    • Place of Presentation
      パリ国際会議場
    • Related Report
      2009 Annual Research Report
  • [Presentation] Neuronal She : a molecular correlate of age-related cognitive decline and spine morphogenesis2009

    • Author(s)
      森 望
    • Organizer
      Symposium on Biological Complexity : Processes of Aging
    • Place of Presentation
      アメリカ ソーク研究所
    • Related Report
      2008 Annual Research Report
  • [Presentation] Roles of TDACs (Tubulin deacetylases) in neuronal aging and longevity control2008

    • Author(s)
      森望
    • Organizer
      AACL日韓共同セミナー:アジア老化研究教育拠点形成にむけて
    • Place of Presentation
      ハウステンボス
    • Year and Date
      2008-09-04
    • Related Report
      2009 Final Research Report
  • [Presentation] Roles of TDACs(Tubulin deacetylases)in neuronal aging and longevity control.2008

    • Author(s)
      森 望
    • Organizer
      AACL日韓共同セミナー : アジア老化研究教育拠点形成にむけて
    • Place of Presentation
      ハウステンボス
    • Year and Date
      2008-09-04
    • Related Report
      2008 Annual Research Report
  • [Presentation] Roles and signaling mechanisms of the neural-specific Shc phosphor-tyrosine adaptor in dendritic spine morphogenesis of hippocampal neurons2008

    • Author(s)
      森望
    • Organizer
      アジアパシフィック神経化学会議
    • Place of Presentation
      上海グットホープホテル(中国・上海)
    • Year and Date
      2008-06-25
    • Related Report
      2009 Final Research Report
  • [Presentation] Roles and signaling mechanisms of the neural-specific She phospho-tyrosine adaptor in dendritic spine morphogenesis of hippocampal neurons2008

    • Author(s)
      森 望
    • Organizer
      アジアパシフィック神経化学会議
    • Place of Presentation
      上海グッドホープホテル
    • Year and Date
      2008-06-25
    • Related Report
      2008 Annual Research Report
  • [Presentation] 寿命制御と神経生存におけるHDACsとTDACs2008

    • Author(s)
      森望
    • Organizer
      日本基礎老化学会第31回大会
    • Place of Presentation
      長野県松本文化会館
    • Year and Date
      2008-06-12
    • Related Report
      2009 Final Research Report
  • [Presentation] 寿命制御と神経生存におけるHDAC s とTDAC s2008

    • Author(s)
      森 望
    • Organizer
      日本基礎老化学会第31回大会
    • Place of Presentation
      長野県松本文化会館
    • Year and Date
      2008-06-12
    • Related Report
      2008 Annual Research Report
  • [Presentation] a molecular correlate of age-related cognitive decline and spine morphogenesis2008

    • Author(s)
      森望、Neuronal Shc
    • Organizer
      日韓基礎老化学会合同シンポジウム
    • Place of Presentation
      Yeungnam大学医学部(韓国・テグ市)
    • Year and Date
      2008-05-15
    • Related Report
      2009 Final Research Report
  • [Presentation] Neuronal She : a molecular correlate of age-related cognitive decline and spine morphogenesis2008

    • Author(s)
      森 望
    • Organizer
      日韓基礎老化学会合同シンポジウム
    • Place of Presentation
      デグ市Yeungnam大学医学部
    • Year and Date
      2008-05-15
    • Related Report
      2008 Annual Research Report
  • [Presentation] 寿命制御と神経生存のおけるHDACsとTDACs2007

    • Author(s)
      森望
    • Organizer
      BMB2007日本分子生物学会年会日本生化学大会
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      2007-12-11
    • Related Report
      2009 Final Research Report
  • [Presentation] 寿命制御と神経生存のおけるHDAC s とTDAC s2007

    • Author(s)
      森 望
    • Organizer
      BMB2007日本分子生物学会年会 日本生化学大会
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      2007-12-11
    • Related Report
      2007 Annual Research Report
  • [Presentation] 脳の老化と神経変性におけるチューブリン脱アセチル化酵素(TDACs)2007

    • Author(s)
      森望
    • Organizer
      第30回日本基礎老化学会
    • Place of Presentation
      北海道厚生年金会館
    • Year and Date
      2007-06-21
    • Related Report
      2009 Final Research Report
  • [Presentation] 脳の老化と神経変性におけるチューブリン脱アセチル化酵素 (TDACs)2007

    • Author(s)
      森 望
    • Organizer
      第30回日本基礎老化学会
    • Place of Presentation
      北海道厚生年金会館
    • Year and Date
      2007-06-21
    • Related Report
      2007 Annual Research Report
  • [Presentation] In vitro neuronal aging: long-term cultured hipPocampal neurons of an in vitro aging model2007

    • Author(s)
      Shiraishi-Yamaguchi Y
    • Organizer
      北米神経科学会
    • Place of Presentation
      サンディエゴ国際会議場(アメリカ・サンディエゴ)
    • Related Report
      2009 Final Research Report
  • [Presentation] Shc-related neuronal phosphotyrosine adaptors in brain aging and longevity control2007

    • Author(s)
      森望
    • Organizer
      第8回アジア・オセアニア国際老年学会議
    • Place of Presentation
      北京国際会議センター(中国・北京)
    • Related Report
      2009 Final Research Report
  • [Presentation] Roles of the neuronal phospho-tyrosine signal adaptor, N-Shc/ShcC, in the activity-dependent actin remodeling in the hippocampal post-synatic spines2007

    • Author(s)
      森望
    • Organizer
      北米神経科学学会
    • Place of Presentation
      サンディエゴ国際会議場(アメリカ・サンディエゴ)
    • Related Report
      2009 Final Research Report
  • [Presentation] Shc系アダプター分子による神経活動依存的なアクチン骨格制御2007

    • Author(s)
      森望
    • Organizer
      日本神経科学大会・日本神経化学学会
    • Place of Presentation
      パシフィコ横浜
    • Related Report
      2009 Final Research Report 2007 Annual Research Report
  • [Presentation] リン酸化チロシンアダプター分子Shcを介したスパイン形成制御に関わるシグナル伝達経路2007

    • Author(s)
      森望、山口陽子
    • Organizer
      日本神経科学大会・日本神経化学学会
    • Place of Presentation
      パシフィコ横浜
    • Related Report
      2009 Final Research Report 2007 Annual Research Report
  • [Presentation] In vitro neuronal aging: Long-term cultured hippocampal neurons of an in vitro aging model2007

    • Author(s)
      Shiraishi-Yamaguchi Y
    • Organizer
      北米神経科学会
    • Place of Presentation
      サンディエゴ国際会議場
    • Related Report
      2007 Annual Research Report
  • [Presentation] Shc-related neuronal phosphotyrosine adaptors in brain aging and longevity control2007

    • Author(s)
      森 望
    • Organizer
      第8回アジア・オセアニア国際老年学会議
    • Place of Presentation
      北京国際会議センター
    • Related Report
      2007 Annual Research Report
  • [Presentation] Roles of the neuronal phospho-tyrosine signal adaptor,N-Sch/ShcC,in the activity-dependent actin remodeling in the hippocampal post-synatic spines2007

    • Author(s)
      森 望
    • Organizer
      北米神経科学学会
    • Place of Presentation
      サンディエゴ国際会議場
    • Related Report
      2007 Annual Research Report
  • [Book] 神経系の加齢変化(第2章第1節)in『新老年学第3版』2009

    • Author(s)
      森望, 大内尉義(編集)
    • Publisher
      東京大学出版会
    • Related Report
      2009 Final Research Report
  • [Book] 月刊 実験医学Vo126 2008年5月号特別寄稿分子遺伝学の巨匠Seymour Benzer- - Methuselahの夢と足跡2008

    • Author(s)
      森 望
    • Total Pages
      6
    • Publisher
      羊土社
    • Related Report
      2008 Annual Research Report
  • [Remarks]

    • URL

      http://www.med.nagasaki-u.ac.jp/anatomyl/index.html

    • Related Report
      2009 Final Research Report

URL: 

Published: 2007-04-01   Modified: 2016-04-21  

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