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Neuroprotection and morphoregulation of centrosome-associated molecules by STB/HAP1 in knock-out or transgenic mice

Research Project

Project/Area Number 16H05118
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field General anatomy (including histology/embryology)
Research InstitutionYamaguchi University

Principal Investigator

SHINODA Koh  山口大学, 大学院医学系研究科, 教授 (40192108)

Co-Investigator(Kenkyū-buntansha) 柳井 章江  山口大学, 大学院医学系研究科, 准教授 (20284854)
升本 宏平  山口大学, 大学院医学系研究科, 講師 (60580529)
Md・Nabiul Islam  山口大学, 大学院医学系研究科, 助教 (80759671)
藤永 竜太郎  山口大学, 大学院医学系研究科, 講師 (30335723)
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥17,940,000 (Direct Cost: ¥13,800,000、Indirect Cost: ¥4,140,000)
Fiscal Year 2018: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Fiscal Year 2017: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2016: ¥11,830,000 (Direct Cost: ¥9,100,000、Indirect Cost: ¥2,730,000)
Keywords斑点小体 / 中心体周囲物質 / 脳 / 視床下部 / 神経変性疾患 / 海馬 / 脊髄 / 運動ニューロン / ハンティンティン / 神経変性 / 後部海馬体 / 中心体 / 中心小体
Outline of Final Research Achievements

Using several cultured cells and HAP1-gene-manipulated mice, cytoplasmic HAP1 expression was clarified to translocate PCM1 from peri-centriole to the stigmoid body (STB) and to make huntingtin dispersed in cytoplasm, and also proven to suppress apoptosis specifically induced by proteasome-inhibition. The neurodegenerative targets including the cerebral cortex, striatum, thalamus, substantia nigra, cerebellum and brainstem/spinal motor neurons were devoid or scanty of STB/HAP1 expression, whereas the brain regions spared from neurodegeneration, including the medial preoptic, hypothalamic, amygdaloid regions and subcortical limbic regions, were rich in STB/HAP1 expression. The hippocampus depends on the subregions; STB/HAP1 is sporadically expressed in the dentate gyrus and Ammon’s horn, while much more expressed in the retrohippocampal regions.

Academic Significance and Societal Importance of the Research Achievements

認知症、パーキンソン病、ハンチントン病等、神経変性疾患は未だ病態も治療法も不明であるが、共通して大脳新皮質、線条体、海馬、視床、黒質、小脳、運動ニューロン等が変性する。変性標的領域に発現が少なく、視床下部等の変性抵抗性領域に広く分布し、HAP1を発現する封入体stigmoid body(STB)を発見した。加齢による神経細胞死誘導の主な原因はプロテアソーム活性低下と考えられ、STB/HAP1は中心体機能を修飾し、この活性阻害による細胞死を特異的に抑制する内在性神経変性保護因子と考えられる。外因とは逆の内因的視点から神経変性疾患の発症脆弱性診断や治療法開発へ向かう新たな突破口になると期待される。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Annual Research Report
  • 2016 Annual Research Report
  • Research Products

    (35 results)

All 2019 2018 2017 2016

All Journal Article (7 results) (of which Int'l Joint Research: 6 results,  Peer Reviewed: 7 results,  Open Access: 4 results,  Acknowledgement Compliant: 1 results) Presentation (28 results) (of which Int'l Joint Research: 1 results,  Invited: 3 results)

  • [Journal Article] Prophylactic effects of vitamin E and coriander (Coriandrum sativum) extract on lead-induced testicular damage in Swiss albino mice2019

    • Author(s)
      Mohammad Rafiqul Islam, Md. Anwar Jahid, Md Zahirul Islam Khan and Md. Nabiul Islam
    • Journal Title

      J Adv Biotechnol Exp Ther

      Volume: 2 Issue: 0 Pages: 31-35

    • DOI

      10.5455/jabet.2018.d22

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Distribution of HAP1-immunoreactive Cells in the Retrosplenial-retrohippocampal Area of Adult Rat Brain and Its Application to a Refined Neuroanatomical Understanding of the Region2018

    • Author(s)
      Wroblewski Greggory、Islam Md. Nabiul、Yanai Akie、Jahan Mir Rubayet、Masumoto Koh-hei、Shinoda Koh
    • Journal Title

      Neuroscience

      Volume: 394 Pages: 109-126

    • DOI

      10.1016/j.neuroscience.2018.10.029

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Morphometry and expression of immunoglobulins-containing plasma cells in the Harderian gland of Birds2018

    • Author(s)
      Mir Rubayet Jahan, Md. Nabiul Islam, Md. Zahirul Islam Khan, Akie Yanai, Koh Shinoda
    • Journal Title

      J Adv Biotechnol Exp Ther

      Volume: 1 Issue: 3 Pages: 55-60

    • DOI

      10.5455/jabet.2018.d10

    • Related Report
      2018 Annual Research Report 2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Immunohistochemical analysis of huntingtin-associated protein 1 in adult rat spinal cord and its regional relationship with androgen receptor.2017

    • Author(s)
      Islam MN, Takeshita Y, Yanai A, Imagawa A, Jahan MR, Wroblewski G, Nemoto J, Fujinaga R, Shinoda K.
    • Journal Title

      Neuroscience

      Volume: 340 Pages: 201-217

    • DOI

      10.1016/j.neuroscience.2016.10.053

    • Related Report
      2017 Annual Research Report 2016 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Effects of task language and second-language proficiency on the neural correlates of phonemic fluency in native Japanese speakers2017

    • Author(s)
      Wroblewski Greggory J.、Matsuo Koji、Hirata Keiko、Matsubara Toshio、Harada Kenichiro、Watanabe Yoshifumi、Shinoda Koh
    • Journal Title

      NeuroReport

      Volume: 28 Issue: 14 Pages: 884-889

    • DOI

      10.1097/wnr.0000000000000852

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Clock Gene Dysregulation Induced by Chronic ER Stress Disrupts β-cell Function.2017

    • Author(s)
      Ohta Y., Taguchi A., Matsumura T., Nakabayashi H., Akiyama M., Yamamoto K., Fujimoto R., Suetomi R., Yanai A., Shinoda K., Tanizawa Y.
    • Journal Title

      EBioMedicine

      Volume: 18 Pages: 146-156

    • DOI

      10.1016/j.ebiom.2017.03.040

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Developmental trajectory of the prenatal lymphoid organs in native chickens: a macro anatomical study.2017

    • Author(s)
      Islam MN, Khan MZI, Jahan MR, Shinoda K.
    • Journal Title

      Asian J. Med. Biol. Res

      Volume: 3 Issue: 4 Pages: 432-436

    • DOI

      10.3329/ajmbr.v3i4.35333

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] マウスHAP1陽性嗅覚遊走性胎生細胞の胎生期脳内移動形態とHAP1欠損マウスにおけるGnRH陽性細胞脳内移動2018

    • Author(s)
      升本宏平,米澤恒成,ナビュール・イスラム,柳井章江,飯田真帆,中河友里,濱崎楓子,篠田晃
    • Organizer
      第124回日本解剖学会総会・全国学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Novel utility of HAP1-immunoreactivity in areal and laminar demarcation of the retrosplenial-retrohippocampal area in adult rat brain.2018

    • Author(s)
      Islam Md Nabiul,Greggory Wroblewski, Mir Rubayet Jahan, Naoya Kamimura, Emi Miyasato, Shogo Togawa, Ayako Nakai, Akie Yanai, Koh-hei Masumoto, Abu Md Mamun Tarif, Koh Shinoda.
    • Organizer
      第124回日本解剖学会総会・全国学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] STB/HAP1 のユビキチン-プロテアソ-ム系阻害型細胞死に対する特異的神経細胞保護効果.2018

    • Author(s)
      篠田晃、藤永竜太郎、ナビュール・イスラム、升本宏平、宮本隼伍、柳井章江
    • Organizer
      日本解剖学会第73回中国・四国支部学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Effects of testosterone on androgen receptor expression and the dynamics of intrinsic plasticity in CA1 pyramidal neurons of male rat.2018

    • Author(s)
      Md. Nabiul Islam, Yua Sakimoto, Naoya Kamimura, Ayako Nakai, Koh-hei Masumoto, Akie Yanai, Dai Mitsushima and Koh Shinoda
    • Organizer
      日本解剖学会第73回中国・四国支部学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 正常細胞に存在するSTB/HAP1による中心体周囲物質PCM1の局在変化2018

    • Author(s)
      柳井章江,藤永竜太郎,ナビュール・イスラム,升本宏平,篠田晃
    • Organizer
      第19回ORIGIN 神経科学研究会  夏のワークショップ2018 in 淡路
    • Related Report
      2018 Annual Research Report
  • [Presentation] STB/HAP1の神経細胞保護について2018

    • Author(s)
      篠田 晃,藤永竜太郎、ナビュール・イスラム、米澤恒成、升本宏平、柳井章江
    • Organizer
      第19回ORIGIN 神経科学研究会  夏のワークショップ2018 in 淡路
    • Related Report
      2018 Annual Research Report
  • [Presentation] 培養細胞およびマウス脳内におけるHap1によるPCM1およびhuntingtinの形態解析2018

    • Author(s)
      柳井章江,藤永竜太郎,ナビュール・イスラム,篠田晃
    • Organizer
      日本顕微鏡学会 第74回学術講演会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 脳内ステロイド作用と神経変性を制御するSTB/HAP12018

    • Author(s)
      篠田晃
    • Organizer
      大阪大学大学院・連合小児発達学研究科・分子生物遺伝学特別講演
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] Gonadal hormones affect the dynamics of intrinsic plasticity in the pyramidal neurons of CA1 hippocampal subfield by acting via androgen receptors in male rats.2017

    • Author(s)
      Md Nabiul Islam, Yua Sakimoto, Mir Rubayet Jahan, Amami Imagawa, Akie Yanai, Ryutaro Fujinaga, Dai Mitsushima and Koh Shinoda.
    • Organizer
      第18回 ORIGIN 神経科学研究会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Hap1-immunoreactive olfactory migrating cells during the mouse pre- and neonatal stages, with special reference to relationship with the GnRH-immunoreactive cells.2017

    • Author(s)
      Kosei Yonezawa, Md Nabiul Islam, Akie Yanai, Ryutaro Fujinaga, Nanami Mayeda and Koh Shinoda.
    • Organizer
      第18回 ORIGIN 神経科学研究会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Immunohistochemical distribution of Hap1-immunoreactive olfactory migrating (HOM) cells during pre- and neonatal stages in mouse, and its relationship with GnRH-expressing neurons.2017

    • Author(s)
      Kosei Yonezawa, Md Nabiul Islam, Mako Ishida, Takuya Kurisu, Yoshinori Sakurai, Akie Yanai, Ryutaro Fujinaga and Koh Shinoda.
    • Organizer
      第72回日本解剖学会中四国地方会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Regional distribution of huntingtin-associated protein 1 (HAP1) in adult rat spinal cord and its immunohistochemical relationship with androgen receptor.2017

    • Author(s)
      Md Nabiul Islam, Yukio Takeshita, Amami Imagawa, Mir Rubayet Jahan, Eriko Yoshidome, Akie Yanai, Ryutaro Fujinaga and Koh Shinoda.
    • Organizer
      第72回日本解剖学会中四国地方会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Species differences in AR expression with some newly identified AR-immunoreactive nuclei in MPO/AH areas of adult rodent brain.2017

    • Author(s)
      Mir Rubayet Jahan, Md. Nabiul Islam, Chikahisa Matsuo, Akie Yanai, Ryutaro Fujinaga, Saeka Hashimoto, Koh Shinoda.
    • Organizer
      第123回日本解剖学会総会・全国学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Dynamics of intrinsic plasticity and AR expression in CA1 pyramidal neurons of male rat: Effects of androgen and antiandrogen.2017

    • Author(s)
      Md Nabiul Islam, Yua Sakimoto, Mir Rubayet Jahan, Akie Yanai, Ryutaro Fujinaga, Chisaki Mochida, Dai Mitsushima and Koh Shinoda.
    • Organizer
      第123回日本解剖学会総会・全国学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Immunohistochemical relationship of HOM cells with GnRH-expressing neurons during pre- and neonatal stages in mouse2017

    • Author(s)
      Kosei Yonezawa, Md Nabiul Islam, Akie Yanai, Ryutaro Fujinaga and Koh Shinoda.
    • Organizer
      第123回日本解剖学会総会・全国学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] ステロイドと脳内作用と修飾~神経変性疾患との関連~2017

    • Author(s)
      篠田晃
    • Organizer
      大阪大学医学部特別セミナー
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] Structure and Function of the Stigmoid Body and Huntingtin-Associated Protein: A New Insight for Region-Specific Neurodegeneration in Protein Folding Diseases and Neuroprotection against Capacity-Over Stress to Ubiquitin-Proteasome System.2017

    • Author(s)
      Koh Shinoda
    • Organizer
      Kick-Off Alliance Seminar 2018 between Yamaguchi Univ. Sch. Med. & Univ. Michigan Med. Sch.
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 脳内性ステロイドの個体間種保存適応反応における性分化作用と関連制御構造による神経変性疾患保護2017

    • Author(s)
      篠田 晃
    • Organizer
      第122回日本解剖学会総会・全国学術総会: シンポジウム 「個と絆を制御する神経・内分泌ネットワークの探求」
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] HAP1 immunoreactive cells migrating along the peripheral pathway of the primary olfactory system in the pre-and neonatal mice.2017

    • Author(s)
      Kosei Yonezawa, Md. Nabiul Islam, Akie Yanai, Ryutaro Fujinaga, Koh Shinoda
    • Organizer
      第122回日本解剖学会総会・全国学術集会
    • Related Report
      2016 Annual Research Report
  • [Presentation] Characterization of HAP1-immunoreactive cells in the rat spinal cord with special emphasis on its regional relationship with AR.2017

    • Author(s)
      Md. Nabiul Islam, Yukio Takeshita, Akie Yanai, Amami Imagawa, Mir Rubayet Jahan, Kosei Yonezawa, Ryutaro Fujinaga, Koh Shinoda,
    • Organizer
      第122回日本解剖学会総会・全国学術集会
    • Related Report
      2016 Annual Research Report
  • [Presentation] Effects of task language and English proficiency on cortical activity during phonemic fluency tasks in Japanese-English bilinguals.2017

    • Author(s)
      Greggory Wroblewski, Koji Matsuo, Keiko Hirata, Toshio Matsubara, Kenichiro Harada, Yoshifumi Watanabe, Koh Shinoda.
    • Organizer
      第122回日本解剖学会総会・全国学術集会
    • Related Report
      2016 Annual Research Report
  • [Presentation] 細胞ストレス負荷によるHAP1の細胞内発現形態変化と細胞死抑制効果~特にプロテアソーム活性低下との関連~2017

    • Author(s)
      藤永竜太郎、柳井章江、原田佳代子、Md Nabiul Islam、篠田晃
    • Organizer
      第122回日本解剖学会総会・全国学術集会
    • Related Report
      2016 Annual Research Report
  • [Presentation] HAP1による中心体関連物質PCM1及びhuntingtinの形態制御2017

    • Author(s)
      柳井章江、藤永竜太郎、石田眞子、Md Nabiul Islam、篠田 晃
    • Organizer
      第122回日本解剖学会総会・全国学術集会
    • Related Report
      2016 Annual Research Report
  • [Presentation] Immunohistochemical analysis of huntingtin-associated protein 1 (HAP1) in the adult male rat spinal cord; with an emphasis on its regional relationship to androgen receptor.2016

    • Author(s)
      Md. Nabiul Islam, Yukio Takeshita, Akie Yanai, Ryutaro Fujinaga, Koh Shinoda,
    • Organizer
      第17回ORIGIN 神経科学研究会
    • Related Report
      2016 Annual Research Report
  • [Presentation] STB/HAP1による中心体関連蛋白質PCM1, huntingtinの形態制御2016

    • Author(s)
      柳井章江、藤永竜太郎、Md Nabiul Islam、篠田 晃
    • Organizer
      第17回ORIGIN 神経科学研究会
    • Related Report
      2016 Annual Research Report
  • [Presentation] Altered androgen receptor expression and intrinsic excitability of the hippocampal CA1 pyramidal neurons in androgen-manipulated male rats.2016

    • Author(s)
      Md. Nabiul Islam, Yuya Sakimoto, Akie Yanai, Ryutaro Fujinaga, Dai Mitsushima, Koh Shinoda
    • Organizer
      第59回日本神経化学会大会
    • Related Report
      2016 Annual Research Report
  • [Presentation] Gonadal hormones affect androgen receptor expression and intrinsic plasticity in the CA1 hippocampal subfield of male rat.2016

    • Author(s)
      Md. Nabiul Islam, Yuya Sakimoto, Akie Yanai, Amami Imagawa, Ryutaro Fujinaga, Dai Mitsushima, Koh Shinoda
    • Organizer
      第70回日本解剖学会中四国地方会
    • Related Report
      2016 Annual Research Report
  • [Presentation] Species difference in androgen receptor expression in the medial preoptic and anterior hypothalamic areas of adult male and female rodents.2016

    • Author(s)
      Mir Rubayet Jahan, Md Nabiul Islam, Joe Nemoto, Yanai Akie, Fujinaga Ryutaro, Koh Shinoda
    • Organizer
      第43回日本神経内分泌学会学術集会
    • Related Report
      2016 Annual Research Report

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Published: 2016-04-21   Modified: 2024-12-25  

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