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Elucidating the mechanisms underlying the neural circuit reorganization after brain injuries

Research Project

Project/Area Number 17H04985
Research Category

Grant-in-Aid for Young Scientists (A)

Allocation TypeSingle-year Grants
Research Field Nerve anatomy/Neuropathology
Research InstitutionNiigata University

Principal Investigator

Ueno Masaki  新潟大学, 脳研究所, 教授 (40435631)

Project Period (FY) 2017-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥23,660,000 (Direct Cost: ¥18,200,000、Indirect Cost: ¥5,460,000)
Fiscal Year 2020: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2018: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2017: ¥9,100,000 (Direct Cost: ¥7,000,000、Indirect Cost: ¥2,100,000)
Keywords皮質脊髄路 / 脳梗塞 / 神経回路 / 可塑性 / 再編 / 神経科学 / 脳神経疾患 / 脳障害
Outline of Final Research Achievements

Rewiring of neural circuits is one of the key processes to promote functional recovery after brain injuries. However, the mechanisms underlying the rewiring are not fully understood. The aim of this study is to reveal the structures and functions of rewired circuits, and the mechanism of rewiring after the injury. In particular, we examined the structures and functions of corticospinal circuit, the main neural pathway for voluntary movement, in control and injured brain. We first found that the corticospinal circuit consists of multiple pathways and connections, and each has distinct sensorimotor function. After the injury, we examined the degree and patterns of rewiring, and found several molecules and methods to promote axonal growth. Our data will contribute to understand the mechanism of neural reorganization and develop novel strategies to restore neural network and functions after the injuries.

Academic Significance and Societal Importance of the Research Achievements

脳や脊髄が障害されると、神経回路が破綻し、機能の障害を引き起こす。脳が回路を新たに形成する能力はきわめて限定的であり、機能を回復する根本的な治療法は未だ確立されていない。近年の研究から、障害後に残存した回路の可塑的・代償的な変化が、失われた機能を変容させうることがわかってきており、回路再編の制御が機能回復へ向けた治療の標的となることが期待されている。本研究では、中枢神経障害後の回路の再編機序と再編を促進する方法論の一端を明らかにした。この成果は、脳障害後に神経回路の再編を促し機能回復をもたらす原理の理解や治療戦略の確立に貢献すると期待される。

Report

(5 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Annual Research Report
  • 2018 Annual Research Report
  • 2017 Annual Research Report
  • Research Products

    (59 results)

All 2021 2020 2019 2018 2017 Other

All Int'l Joint Research (6 results) Journal Article (16 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 10 results,  Open Access: 9 results) Presentation (33 results) (of which Int'l Joint Research: 6 results,  Invited: 17 results) Remarks (4 results)

  • [Int'l Joint Research] Burke Neurological Institute(米国)

    • Related Report
      2020 Annual Research Report
  • [Int'l Joint Research] Burke Neurological Institute(米国)

    • Related Report
      2019 Annual Research Report
  • [Int'l Joint Research] シンシナティ小児病院(米国)

    • Related Report
      2018 Annual Research Report
  • [Int'l Joint Research] シンシナティ大学(米国)

    • Related Report
      2018 Annual Research Report
  • [Int'l Joint Research] ソーク研究所(米国)

    • Related Report
      2018 Annual Research Report
  • [Int'l Joint Research] シンシナティ小児病院/シンシナティ大学/ソーク研究所(米国)

    • Related Report
      2017 Annual Research Report
  • [Journal Article] Neuro-immune circuitry to restore in the brain and spinal cord injuries2021

    • Author(s)
      Ueno M
    • Journal Title

      Int Immunol

      Volume: in press Issue: 6 Pages: 311-325

    • DOI

      10.1093/intimm/dxab017

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Olig2-Induced Semaphorin Expression Drives Corticospinal Axon Retraction After Spinal Cord Injury2020

    • Author(s)
      Ueno Masaki、Nakamura Yuka、Nakagawa Hiroshi、Niehaus Jesse K、Maezawa Mari、Gu Zirong、Kumanogoh Atsushi、Takebayashi Hirohide、Lu Qing Richard、Takada Masahiko、Yoshida Yutaka
    • Journal Title

      Cerebral Cortex

      Volume: 30 Issue: 11 Pages: 5702-5716

    • DOI

      10.1093/cercor/bhaa142

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Netrin-G1 regulates microglial accumulation along axons and supports the survival of layer V neurons in the postnatal mouse brain.2020

    • Author(s)
      Fujita, Y., Nakanishi, T., Ueno, M., Itohara, S., and Yamashita, T.
    • Journal Title

      Cell Reports

      Volume: 31 Issue: 4 Pages: 107580-107580

    • DOI

      10.1016/j.celrep.2020.107580

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Inhibition of HDAC increases BDNF expression and promotes neuronal rewiring and functional recovery after brain injury2020

    • Author(s)
      Sada Naoki、Fujita Yuki、Mizuta Nanano、Ueno Masaki、Furukawa Takahisa、Yamashita Toshihide
    • Journal Title

      Cell Death & Disease

      Volume: 11 Issue: 8 Pages: 655-655

    • DOI

      10.1038/s41419-020-02897-w

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Combinational Approach of Genetic SHP-1 Suppression and Voluntary Exercise Promotes Corticospinal Tract Sprouting and Motor Recovery Following Brain Injury2020

    • Author(s)
      Tanaka Takashi、Ito Tetsufumi、Sumizono Megumi、Ono Munenori、Kato Nobuo、Honma Satoru、Ueno Masaki
    • Journal Title

      Neurorehabilitation and Neural Repair

      Volume: 34 Issue: 6 Pages: 558-570

    • DOI

      10.1177/1545968320921827

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] 中枢神経障害による神経回路の再編と機能回復2020

    • Author(s)
      上野将紀
    • Journal Title

      新潟医学会雑誌

      Volume: 134 Pages: 7-12

    • NAID

      120006940016

    • Related Report
      2020 Annual Research Report
  • [Journal Article] 随意運動をになう神経回路の再建 -基礎研究の現状と課題-2020

    • Author(s)
      上野将紀
    • Journal Title

      新潟県医師会報

      Volume: 842 Pages: 2-7

    • Related Report
      2020 Annual Research Report
  • [Journal Article] 動きを生み出す脳の仕組みと謎2020

    • Author(s)
      上野将紀
    • Journal Title

      脳研コラム

      Volume: なし

    • Related Report
      2019 Annual Research Report
    • Open Access
  • [Journal Article] Skilled movements in mice require inhibition of corticospinal axon collateral formation in the spinal cord by semaphorin signaling.2019

    • Author(s)
      Gu Z, Ueno M, Klinefelter K, Mamidi M, Yagi T, Yoshida Y.
    • Journal Title

      J Neurosci

      Volume: 39 Issue: 45 Pages: 8885-8899

    • DOI

      10.1523/jneurosci.2832-18.2019

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Dual functions of microglia in the formation and refinement of neural circuits during development2019

    • Author(s)
      Konishi H, Kiyama H, Ueno M
    • Journal Title

      Int J Developmental Neuroscience

      Volume: 印刷中 Issue: 1 Pages: 18-25

    • DOI

      10.1016/j.ijdevneu.2018.09.009

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] 脊髄損傷と自律神経-臓器-免疫連関2019

    • Author(s)
      上野将紀
    • Journal Title

      実験医学

      Volume: 36 Pages: 2122-2128

    • Related Report
      2019 Annual Research Report
  • [Journal Article] Corticospinal circuits from the sensory and motor cortices differentially regulate skilled movements through distinct spinal interneurons.2018

    • Author(s)
      Ueno M, Nakamura Y, Li J, Gu Z, Niehaus J, Maezawa M, Crone SA, Goulding M, Baccei ML, Yoshida Y.
    • Journal Title

      Cell Reports

      Volume: 23 Issue: 5 Pages: 1286-1300

    • DOI

      10.1016/j.celrep.2018.03.137

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] MARCKSL1 regulates spine formation in the amygdala and controls the hypothalamic-pituitary-adrenal axis and anxiety-like behaviors.2018

    • Author(s)
      Tanaka T, Shimizu S, Ueno M, Fujihara Y, Ikawa M, Miyata S.
    • Journal Title

      EBioMedicine

      Volume: 30 Pages: 62-73

    • DOI

      10.1016/j.ebiom.2018.03.018

    • NAID

      120006957428

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] 脳・脊髄の障害による神経-免疫制御システムの破綻2018

    • Author(s)
      上野将紀
    • Journal Title

      実験医学

      Volume: 36 Pages: 370-376

    • Related Report
      2017 Annual Research Report
  • [Journal Article] 特集 ミクログリアと精神・神経疾患 ミクログリアと脳発達2017

    • Author(s)
      上野将紀
    • Journal Title

      BRAIN and NERVE

      Volume: 69 Issue: 9 Pages: 985-997

    • DOI

      10.11477/mf.1416200858

    • ISSN
      1344-8129, 1881-6096
    • Year and Date
      2017-09-01
    • Related Report
      2017 Annual Research Report
  • [Journal Article] Rewiring of neural circuits and functional recovery following brain and spinal cord injuries2017

    • Author(s)
      上野将紀
    • Journal Title

      Leading Author's

      Volume: 6 Pages: e003

    • DOI

      10.7875/leading.author.6.e003

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] Rewiring of neural circuits in CNS injuries.2020

    • Author(s)
      Ueno M
    • Organizer
      Virtual DANDRITE lecture
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Dysfunction of autonomic circuits and immune system in spinal cord injury.2020

    • Author(s)
      Ueno M
    • Organizer
      FENS 2020
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Neuroprotective function of microglia in the postnatal brain.2020

    • Author(s)
      Fujita Y, Ueno M, Yamashita T
    • Organizer
      FENS 2020
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 神経回路の再建と機能回復2020

    • Author(s)
      上野将紀
    • Organizer
      第8回神経と免疫を語る会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] Comparison of corticospinal circuit between healthy and damaged brain.2020

    • Author(s)
      Sato T, Nakamura Y, Yoshida Y, Ueno M
    • Organizer
      生理研・脳研・霊長研合同シンポジウム
    • Related Report
      2020 Annual Research Report
  • [Presentation] 中枢神経障害後の運動回路再建の試み2019

    • Author(s)
      上野将紀
    • Organizer
      第42回日本分子生物学会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 自発的な身体運動は脳損傷後の機能回復を効果的に促進させる2019

    • Author(s)
      田中 貴士、上野将紀、本間 智
    • Organizer
      第24回日本基礎理学療法学会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 巧緻運動を司る皮質脊髄路の接続-機能と再編2019

    • Author(s)
      上野将紀、中村由香、佐藤時春、吉田富
    • Organizer
      第24回日本基礎理学療法学会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 外的・内的要因を標的にした脊髄損傷後の皮質脊髄路の再生効果の検証2019

    • Author(s)
      中村由香、上野将紀、吉田富
    • Organizer
      第24回日本基礎理学療法学会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 中枢神経障害による神経回路の再編と機能回復2019

    • Author(s)
      上野将紀
    • Organizer
      第742回新潟医学会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 脊髄損傷におけるSemaphorinによる軸索再生の阻害2019

    • Author(s)
      中村由香、上野将紀、中川浩、Jesse Niehaus、竹林浩秀、Qing R. Lu、高田昌彦、吉田富
    • Organizer
      第20回ORIGIN神経科学研究会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 中枢神経障害後の運動回路再建の試み2019

    • Author(s)
      上野将紀
    • Organizer
      リエゾンラボ炎症シンポジウム
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] Targeting extrinsic and intrinsic barriers to axon regeneration after spinal cord injury.2019

    • Author(s)
      Nakamura Y, Ueno M, Niehaus J, Zheng Y, Yoshida Y
    • Organizer
      Neuro2019
    • Related Report
      2019 Annual Research Report
  • [Presentation] Neuroprotective function of microglia in the developmental brain.2019

    • Author(s)
      Fujita Y, Ueno M, Nakanishi T, Yamashita T
    • Organizer
      Neuro2019
    • Related Report
      2019 Annual Research Report
  • [Presentation] 巧緻運動をになう皮質脊髄路の構成と再編2019

    • Author(s)
      佐藤時春、中村由香、吉田富、上野将紀
    • Organizer
      第60回新潟生化学懇話会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 脊髄損傷後の転写因子によるSemaphorinの発現制御と軸索再生阻害2019

    • Author(s)
      中村由香、上野将紀、中川浩、Jesse Niehaus、竹林浩秀、Qing R. Lu、高田昌彦、吉田富
    • Organizer
      第60回新潟生化学懇話会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Functional dissection of corticospinal circuit for skilled motor behavior.2019

    • Author(s)
      Ueno M, Nakamura Y, Li J, Gu Z, Niehaus J, Maezawa M, Crone S, Goulding M, Baccei M, Yoshida Y.
    • Organizer
      第9回 脳研究所国際シンポジウム
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 脳卒中による運動回路の再編と機能の描出2019

    • Author(s)
      上野将紀
    • Organizer
      第44回日本脳卒中学会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Genetic and functional dissection of corticospinal circuit for skilled motor behavior.2018

    • Author(s)
      Ueno M, Nakamura Y, Li J, Gu Z, Niehaus J, Maezawa M, Crone S, Goulding M, Baccei M, Yoshida Y.
    • Organizer
      Neuroscience 2018
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 脊髄の障害による神経-免疫連関の破綻2018

    • Author(s)
      上野将紀
    • Organizer
      第1回生体システム連関研究会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 巧みな動作を生み出す皮質脊髄路の多様な接続様式の形成2018

    • Author(s)
      上野将紀
    • Organizer
      第91回日本生化学会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 脊髄の障害による神経回路の再編と免疫抑制2018

    • Author(s)
      上野将紀
    • Organizer
      第83 回日本インターフェロン・サイトカイン学会学術集会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 巧緻運動を制御する皮質脊髄路の構成と動作原理.Genetic and functional dissection of corticospinal circuit for skilled motor behavior.2018

    • Author(s)
      Ueno M, Nakamura Y, Li J, Gu Z, Niehaus J, Maezawa M, Crone S, Goulding M, Baccei M, Yoshida Y.
    • Organizer
      第41回日本神経科学大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 脳発生における神経保護作用2018

    • Author(s)
      Fujita Y, Ueno M, Nakanishi T, Yamashita T.
    • Organizer
      第41回日本神経科学大会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 脊髄損傷による自律神経回路の再編と免疫抑制2018

    • Author(s)
      上野将紀
    • Organizer
      第2回感覚免疫学研究会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 脳脊髄障害後の神経回路の再編と機能2018

    • Author(s)
      上野将紀
    • Organizer
      神戸大学大学院セミナー
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 中枢神経の障害による神経回路の再編と機能の変容2018

    • Author(s)
      上野将紀
    • Organizer
      遺伝子改変動物分野サイエンスセミナー
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 脳脊髄の障害と再生2018

    • Author(s)
      上野将紀
    • Organizer
      麻布大学大学院特別講義
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Genetic and functional dissection of corticospinal circuit for skilled motor behavior2018

    • Author(s)
      Ueno M, Ueno-Nakamura Y, Li J, Gu Z, Niehaus J, Maezawa M, Crone S, Goulding M, Baccei M, Yoshida Y
    • Organizer
      Keystone symposium 2016 State of the Brain: Genetic Dissection of Brain Circuits and Behavior in Health and Disease (A2)
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Functional dissection of corticospinal circuit for skilled motor behavior2017

    • Author(s)
      Ueno M, Ueno-Nakamura Y, Li J, Gu Z, Niehaus J, Maezawa M, Crone S, Goulding M, Baccei M, Yoshida Y
    • Organizer
      次世代脳プロジェクト 2017年度冬のシンポジウム
    • Related Report
      2017 Annual Research Report
  • [Presentation] 脳・脊髄の障害による神経回路の再編と機能回復2017

    • Author(s)
      上野将紀
    • Organizer
      第2回 個体の中の細胞社会学セミナー
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] 巧緻運動を担う皮質脊髄路の接続と動作原理2017

    • Author(s)
      上野将紀
    • Organizer
      第18回 ORIGIN 神経科学研究会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Rewiring of sympathetic circuitry causes immune suppression following spinal cord injury2017

    • Author(s)
      Ueno M, Ueno-Nakamura Y, Niehaus J, Popovich PG, Yoshida Y
    • Organizer
      第40回日本神経科学大会
    • Related Report
      2017 Annual Research Report
  • [Remarks] 新潟大学脳研究所 システム脳病態学分野上野研究室 Research

    • URL

      http://www.bri.niigata-u.ac.jp/~system_neurodis/ueno/Research

    • Related Report
      2020 Annual Research Report
  • [Remarks] 動きを生み出す脳の仕組みと謎

    • URL

      https://www.bri.niigata-u.ac.jp/column/001306.html

    • Related Report
      2019 Annual Research Report
  • [Remarks]

    • URL

      http://www.bri.niigata-u.ac.jp/~system_neurodis/ueno/home.html

    • Related Report
      2018 Annual Research Report
  • [Remarks] 巧みな動作のもとになる,多様な神経回路を発見しました

    • URL

      http://www.bri.niigata-u.ac.jp/result/molepath/001012.html

    • Related Report
      2018 Annual Research Report

URL: 

Published: 2017-04-28   Modified: 2022-01-27  

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