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Understanding Neural Circuit Alterations Caused by Chronic Nicotine Exposure from the Developmental Period

Research Project

Project/Area Number 20H03410
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 48010:Anatomy-related
Research InstitutionHokkaido University

Principal Investigator

Yamasaki Miwako  北海道大学, 医学研究院, 准教授 (10431305)

Co-Investigator(Kenkyū-buntansha) 宮崎 太輔  北海道大学, 保健科学研究院, 准教授 (90374230)
Project Period (FY) 2020-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥17,550,000 (Direct Cost: ¥13,500,000、Indirect Cost: ¥4,050,000)
Fiscal Year 2023: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2022: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Keywordsシナプス / ニコチン / アセチルコリン / 神経伝達 / アセチルコリン受容体 / ニコチン性アセチルコリン受容体
Outline of Research at the Start

ニコチン性アセチルコリン受容体(nAChR)は、タバコの主成分であるニコチンと結合することにより様々な神経伝達修飾作用を及ぼす。よく知られたニコチン依存に加え、近年では発達期からのニコチン曝露がオピオイド系を始めとする薬物依存への道筋をつけるという新たな可能性が示唆されているが、その生物学的なメカニズムや脳内でのnAChRの局在やその分子機構にも未だ不明な点が多い。本研究ではnAChRを介した神経伝達修飾の解剖学的な基盤を示し、発達期からのニコチン曝露が神経回路にどのような構造的・機能的な変容をもたらすかを明らかにする。

Outline of Final Research Achievements

icotinic acetylcholine receptors exert various neurotransmitter-modifying effects by binding to nicotine, the main component of tobacco. In addition to the well-known nicotine dependence, it has recently been suggested that nicotine exposure from the developmental period may provide a new possibility of a pathway to opioid and other drug dependence, but the biological mechanism, its localization in the brain, and its molecular mechanisms are still unknown. In this study, we aim to elucidate the structural and functional mechanisms of neurotransmitter modification via nicotinic acetylcholine receptors and how nicotine exposure from the developmental period alters neural circuits. a3b4 receptors, which are thought to define the upper limit of nicotine intake. The expression patterns of these receptors, which are thought to regulate the upper limit of nicotine intake, were clarified in the adult mouse brain.

Academic Significance and Societal Importance of the Research Achievements

ニコチン依存に関わるニコチン性アセチルコリン受容体の脳内での発現パターンを理解することは、依存症のメカニズムを解明し、より効果的な対策を講じるための重要なステップとなります。例えば、特定の受容体に作用する新しい治療薬を開発することで、より効果的で副作用の少ない治療法が提供できるようになります。また受容体の発現パターンに基づく治療法の発展により、依存症からの回復が促進され、精神的健康の改善が期待されます。さらに依存症予防策の強化につながり、関連する医療費や社会的コストが削減されます。今回得られた解剖学的な知見を活用することで、社会全体の健康と福祉を向上させることが期待されます。

Report

(5 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Annual Research Report
  • 2021 Annual Research Report
  • 2020 Annual Research Report
  • Research Products

    (36 results)

All 2024 2023 2022 2021 2020 2019 Other

All Int'l Joint Research (7 results) Journal Article (19 results) (of which Int'l Joint Research: 6 results,  Peer Reviewed: 19 results,  Open Access: 17 results) Presentation (10 results) (of which Int'l Joint Research: 1 results,  Invited: 1 results)

  • [Int'l Joint Research] エジンバラ大学(英国)

    • Related Report
      2023 Annual Research Report
  • [Int'l Joint Research] オーフス大学(デンマーク)

    • Related Report
      2023 Annual Research Report
  • [Int'l Joint Research] アルベルト・アインシュタイン医学校/イェール大学(米国)

    • Related Report
      2022 Annual Research Report
  • [Int'l Joint Research] エジンバラ大学(英国)

    • Related Report
      2022 Annual Research Report
  • [Int'l Joint Research] オーフス大学(デンマーク)

    • Related Report
      2022 Annual Research Report
  • [Int'l Joint Research] アルベルト・アインシュタイン医学校/イェール大学(米国)

    • Related Report
      2021 Annual Research Report
  • [Int'l Joint Research] Yale大学(米国)

    • Related Report
      2020 Annual Research Report
  • [Journal Article] Enhancement of Haloperidol-Induced Catalepsy by GPR143, an L-Dopa Receptor, in Striatal Cholinergic Interneurons2024

    • Author(s)
      Arai Masami、... 、Kambe Yuki、... 、Goshima Yoshio
    • Journal Title

      The Journal of Neuroscience

      Volume: 44 Issue: 11 Pages: 1504-1523

    • DOI

      10.1523/jneurosci.1504-23.2024

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Execution of new trajectories toward a stable goal without a functional hippocampus.2023

    • Author(s)
      Duszkiewicz, A.J., Rossato, J.I., Moreno, A., Takeuchi, T., Yamasaki, M., Genzel, L., Spooner, P., Canals, S., and Morris, R.G.M.
    • Journal Title

      Hippocampus

      Volume: 33 Issue: 6 Pages: 769-786

    • DOI

      10.1002/hipo.23497

    • Related Report
      2023 Annual Research Report 2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] All-synchronized picosecond pulses and time-gated detection improve the spatial resolution of two-photon STED microscopy in brain tissue imaging2023

    • Author(s)
      Hirokazu Ishii、Kohei Otomo、Ching-Pu Chang、Miwako Yamasaki、Masahiko Watanabe、Hiroyuki Yokoyama、Tomomi Nemoto
    • Journal Title

      PLOS ONE

      Volume: 18(8) Issue: 8 Pages: 7462-7467

    • DOI

      10.1371/journal.pone.0290550

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Glyoxal fixation: An approach to solve immunohistochemical problem in neuroscience research2023

    • Author(s)
      Konno Kohtarou、Yamasaki Miwako、Miyazaki Taisuke、Watanabe Masahiko
    • Journal Title

      Science Advances

      Volume: 9 Issue: 28 Pages: 1-14

    • DOI

      10.1126/sciadv.adf7084

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Regulation of NETosis and Inflammation by Cyclophilin D in Myeloperoxidase‐Positive Antineutrophil Cytoplasmic Antibody?Associated Vasculitis2022

    • Author(s)
      Kudo Takashi、Nakazawa Daigo、Watanabe‐Kusunoki Kanako、Kanda Masatoshi、Shiratori‐Aso Satoka、Abe Nobuya、Nishio Saori、Koga Jun‐ichiro、Iwasaki Sari、Tsuji Takahiro、Fukasawa Yuichiro、Yamasaki Miwako、Watanabe Masahiko、Masuda Sakiko、Tomaru Utano、Murakami Masaaki、Aratani Yasuaki、Ishizu Akihiro、Atsumi Tatsuya
    • Journal Title

      Arthritis & Rheumatology

      Volume: 75 Issue: 1 Pages: 71-83

    • DOI

      10.1002/art.42314

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Single-scan volumetric imaging throughout thick tissue specimens by one-touch installable light-needle creating device2022

    • Author(s)
      Chang Ching-Pu、Otomo Kohei、Kozawa Yuichi、Ishii Hirokazu、Yamasaki Miwako、Watanabe Masahiko、Sato Shunichi、Enoki Ryosuke、Nemoto Tomomi
    • Journal Title

      Scientific Reports

      Volume: 12 Issue: 1 Pages: 10468-10468

    • DOI

      10.1038/s41598-022-14647-3

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Histochemical Characterization of the Dorsal Raphe-Periaqueductal Grey Dopamine Transporter Neurons Projecting to the Extended Amygdala2022

    • Author(s)
      Zhao Qin、Ito Tetsufumi、Soko Chika、Hori Yoshie、Furuyama Takafumi、Hioki Hiroyuki、Konno Kohtarou、Yamasaki Miwako、Watanabe Masahiko、Ohtsuka Satoshi、Ono Munenori、Kato Nobuo、Yamamoto Ryo
    • Journal Title

      eneuro

      Volume: 9 Issue: 3 Pages: ENEURO.0121-22.2022

    • DOI

      10.1523/eneuro.0121-22.2022

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Behavioral characteristics of dopamine D5 receptor knockout mice: locomotor activity, working memory, learning, and impulsivity-related behaviors2022

    • Author(s)
      Sasamori H., Asakura T., Sugiura C., Bouchekioua Y., Nishitani N., Sato M., Yoshida T., Yamasaki M., Terao A., Watanabe M., Ohmura Y., and Yoshioka M.
    • Journal Title

      Scientific Reports

      Volume: 12 Issue: 1 Pages: 6014-6014

    • DOI

      10.1038/s41598-022-10013-5

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] L-DOPA-Induced Neurogenesis in the Hippocampus Is Mediated Through GPR143, a Distinct Mechanism of Dopamine.2022

    • Author(s)
      Kasahara Y, Masukawa D, Kobayashi K, Yamasaki M, Watanabe M, Goshima Y.
    • Journal Title

      Stem Cells.

      Volume: 40 Issue: 2 Pages: 215-226

    • DOI

      10.1093/stmcls/sxab013

    • Related Report
      2022 Annual Research Report 2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Activation of Extrasynaptic Kainate Receptors Drives Hilar Mossy Cell Activity.2022

    • Author(s)
      Ramos C, Lutzu S, Yamasaki M, Yanagawa Y, Sakimura K, Tomita S, Watanabe M, Castillo PE.
    • Journal Title

      J Neurosci.

      Volume: 42 Issue: 14 Pages: 2872-2884

    • DOI

      10.1523/jneurosci.0922-21.2022

    • Related Report
      2022 Annual Research Report 2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] SIPA1L1/SPAR1 Interacts with the Neurabin Family of Proteins and is Involved in GPCR Signaling2022

    • Author(s)
      Matsuura K., Kobayashi S., Konno K., Yamasaki M., Horiuchi T., Senda T., Hayashi T., Satoh K., Arima-Yoshida F., Iwasaki K., Negishi L., Yasui-Shimizu N., Kohu K., Kawahara S., Kirino Y., Nakamura T., Watanabe M., Yamamoto T., Manabe T. and Akiyama T.
    • Journal Title

      The Journal of Neuroscience

      Volume: 42 Issue: 12 Pages: 2448-2473

    • DOI

      10.1523/jneurosci.0569-21.2022

    • Related Report
      2022 Annual Research Report 2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Spike firing attenuation of serotonin neurons in learned helplessness rats is reversed by ketamine2021

    • Author(s)
      Hashimoto Kouichi、Yamawaki Yosuke、Yamaoka Kenji、Yoshida Takayuki、Okada Kana、Tan Wanqin、Yamasaki Miwako、Matsumoto-Makidono Yoshiko、Kubo Reika、Nakayama Hisako、Kataoka Tsutomu、Kanematsu Takashi、Watanabe Masahiko、Okamoto Yasumasa、Morinobu Shigeru、Aizawa Hidenori、Yamawaki Shigeto
    • Journal Title

      Brain Communications

      Volume: 3 Issue: 4 Pages: 1-15

    • DOI

      10.1093/braincomms/fcab285

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] mGluR1 signaling in cerebellar Purkinje cells: class FormattedString { value: Subcellular organization and involvement in cerebellar function and disease }2021

    • Author(s)
      Yamasaki Miwako、Aiba Atsu、Kano Masanobu、Watanabe Masahiko
    • Journal Title

      Neuropharmacology

      Volume: 194 Pages: 108629-108629

    • DOI

      10.1016/j.neuropharm.2021.108629

    • URL

      https://localhost/en/publications/421e1763-b575-4342-8562-643cf562d1b0

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Kv11 (ether-a-go-go-related gene) voltage-dependent K + channels promote resonance and oscillation of subthreshold membrane potentials2021

    • Author(s)
      Matsuoka Toshinori, Yamasaki Miwako, Abe Manabu, Matsuda Yukiko, Morino Hiroyuki, Kawakami Hideshi, Sakimura Kenji, Watanabe Masahiko, Hashimoto Kouichi
    • Journal Title

      The Journal of Physiology

      Volume: 599(2) Issue: 2 Pages: 547-569

    • DOI

      10.1113/jp280342

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Nectin-2alpha is localized at cholinergic neuron dendrites and regulates synapse formation in the medial habenula2021

    • Author(s)
      Shiotani H., Miyata M., Kameyama T., Mandai K., Yamasaki M., Watanabe M., Mizutani K., Takai Y.
    • Journal Title

      Journal of Comparative Neurology

      Volume: 529 Issue: 2 Pages: 450-477

    • DOI

      10.1002/cne.24958

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] TMEM163 Regulates ATP-Gated P2X Receptor and Behavior.2020

    • Author(s)
      Salm EJ, Dunn PJ, Shan L, Yamasaki M, Malewicz NM, Miyazaki T, Park J, Sumioka A, Hamer RRL, He WW, Morimoto-Tomita M, LaMotte RH, Tomita S.
    • Journal Title

      Cell Rep.

      Volume: 31 Issue: 9 Pages: 1-13

    • DOI

      10.1016/j.celrep.2020.107704

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Compartmentalized Input?Output Organization of Lugaro Cells in the Cerebellar Cortex2020

    • Author(s)
      Miyazaki Taisuke、Yamasaki Miwako、Tanaka Kenji F.、Watanabe Masahiko
    • Journal Title

      Neuroscience

      Volume: in press Issue: 20 Pages: 30332-30325

    • DOI

      10.1016/j.neuroscience.2020.05.026

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Development of an L-type Ca 2+ channel-dependent Ca 2+ transient during the radial migration of cortical excitatory neurons2020

    • Author(s)
      Horigane S, Hamada S, Kamijo S, Yamada H, Yamasaki M, Watanabe M, Bito H, Ohtsuka T, Takemoto-Kimura S
    • Journal Title

      Neurosci Res

      Volume: S0168-0102(20)30391-6 Pages: 30391-6

    • DOI

      10.1016/j.neures.2020.06.003

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Expression mapping, quantification, and complex formation of GluD1 and GluD2 glutamate receptors in adult mouse brain2019

    • Author(s)
      Nakamoto Chihiro、Konno Kohtarou、Miyazaki Taisuke、Nakatsukasa Ena、Natsume Rie、Abe Manabu、Kawamura Meiko、Fukazawa Yugo、Shigemoto Ryuichi、Yamasaki Miwako、Sakimura Kenji、Watanabe Masahiko
    • Journal Title

      Journal of Comparative Neurology

      Volume: 528 Issue: 6 Pages: 1003-1027

    • DOI

      10.1002/cne.24792

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] マウス内側手綱核―脚間核経路におけるニコチン性アセチルコリン受容体の発現2024

    • Author(s)
      山崎美和子、都築明日香、今野幸太郎、宮崎太輔、渡辺雅彦
    • Organizer
      第129回日本解剖学会総会・学術集会
    • Related Report
      2023 Annual Research Report
  • [Presentation] マウス小脳プルキンエ細胞におけるカチオンチャネルTRPC3の発現様式2023

    • Author(s)
      山崎美和子、久井漱誠、今野幸太郎、宮崎太輔、渡辺雅彦
    • Organizer
      第127回日本解剖学会総会・全国学術集会
    • Related Report
      2022 Annual Research Report
  • [Presentation] マウス内側手綱核―脚間核経路におけるニコチン性アセチルコリン受容体の発現2022

    • Author(s)
      都築明日香、山崎美和子、今野幸太郎、宮崎太輔、渡辺雅彦
    • Organizer
      第68回 東北・北海道連合支部学術集会
    • Related Report
      2022 Annual Research Report
  • [Presentation] マウス小脳におけるグルタミン酸受容体GluN3Aの選択的集積にはGluN1サブユニットが必須である2022

    • Author(s)
      山崎美和子、宋暁紅、深谷昌弘、今野幸太郎、宮崎太輔、渡辺雅彦
    • Organizer
      第127回日本解剖学会総会・全国学術集会
    • Related Report
      2021 Annual Research Report
  • [Presentation] mGluR1 is required for strengthening of “winner” and elimination of “loser” climbing fiber synapses in the cerebellum2021

    • Author(s)
      Miwako Yamasaki
    • Organizer
      10th International Meeting on Metabotropic Glutamate Receptors
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 背側線条体の興奮性シナプスの強度設定は種を超えて保存される2021

    • Author(s)
      山崎美和子、宋暁紅、今野幸太郎、渡辺雅彦
    • Organizer
      第67回 東北・北海道連合支部学術集会
    • Related Report
      2021 Annual Research Report
  • [Presentation] ニコチン性アセチルコリン受容体の分子シャペロンTMEM35Aは 成体マウス脳内において細胞選択的に発現している2021

    • Author(s)
      山崎美和子、大坪琴美、今野幸太郎、渡辺雅彦
    • Organizer
      第44回日本神経科学大会
    • Related Report
      2021 Annual Research Report
  • [Presentation] ニコチン性アセチルコリン受容体の分子シャペロンTMEM35Aは成体マウス脳内において細胞選択的に発 現している2021

    • Author(s)
      山崎美和子、大坪琴美、今野幸太郎、渡辺雅彦
    • Organizer
      第126回日本解剖学会総会・全国学術集会 / 第98回日本生理学会大会 合同大会
    • Related Report
      2020 Annual Research Report
  • [Presentation] ニコチン性アセチルコリン受容体の分子シャペロンTMEM35(NACHO)の成体マウス脳における発現解析2020

    • Author(s)
      山崎美和子、大坪琴美、今野幸太郎、渡辺雅彦
    • Organizer
      第43回日本生物学会年会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 神経型ニコチン性アセチルコリン受容体の分子シャペロンTMEM35A(NACHO)の成体マウス脳における発現2020

    • Author(s)
      山崎美和子、大坪琴美、今野幸太郎、渡辺雅彦
    • Organizer
      第93回日本生化学会大会
    • Related Report
      2020 Annual Research Report

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Published: 2020-04-28   Modified: 2025-01-30  

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