Studies on communication between neuroaxons via oligodendrocytes.

2017 Fiscal Year Annual Research Report

• Project Area: Glial assembly: a new regulatory machinery of brain function and disorders
• Project/Area Number: 25117005
• Research Institution: National Institute for Physiological Sciences
• Principal Investigator: 池中 一裕 生理学研究所, 分子細胞生理研究領域, 教授 (00144527)
• Co-Investigator(Kenkyū-buntansha): 山崎 良彦 山形大学, 医学部, 准教授 (10361247) ; 田中 謙二 慶應義塾大学, 医学部(信濃町), 准教授 (30329700) ; 清水 健史 名古屋市立大学, 医学部, 講師 (60398237) ; 小林 憲太 生理学研究所, 行動・代謝分子解析センター, 准教授 (70315662) ; 畑中 伸彦 生理学研究所, システム脳科学研究領域, 助教 (80296053)
• Project Period (FY): 2013-06-28 – 2018-03-31
• Keywords: グリア / 精神疾患 / 神経興奮制御 / 活動電位の伝達速度

Outline of Annual Research Achievements

1)平成29年度は、マウスの口髯除去による大脳皮質感覚野の活動低下、および眼瞼縫合による視神経の活動低下を誘起し、個々のOLが形成する髄鞘が、感覚刺激の増減に応答して変化するかどうかを成体マウスの脳内で解析した。その結果、OLは１本の軸索活動状況に対応して髄鞘形成を変化させるのではなく、その場全体の軸索活動状況に応じて、髄鞘作製様式を決定することが分かった。
2) OL脱分極による軸索伝導促進の機能的意義の検討：平成28年度までに、海馬CA1錐体細胞－海馬台錐体細胞間シナプスにおいて、OL脱分極が長期増強の誘導を促進する可能性があることを見出した。平成29年度では例数を重ねて再現性を確認し、OLの脱分極により長期増強の誘導閾値が低下していることが分かった。また、アーキロドプシンをOL特異的に発現させ、OLの活性化を抑制したときの軸索伝導変化、出力先シナプスにおける変化を検討したところ、２０バースト刺激では、長期増強の大きさがコントロールに比べ優位に現象していた。
4) 我々は、髄鞘のパラノードの構成因子の一つであるNF155に対するコンデジィショナルKOマウスを用いることにより、パラノードを破壊する系を確立している。パラノードの破綻を誘導したマウスに対してマイクロアレイ解析を行い、発現が変動した遺伝子の中で、aquaporin3遺伝子はCopy number variantゲノム解析で精神疾患患者で重複が認められた。これらの結果から、パラノードの破綻―aquaporin3遺伝子の変動―精神疾患の三者間連関が示唆された。これらの結果を踏まえ、平成29年度はaquaporin3を組込んだアデノ随伴ウイルス(AAV)をNF155 cKOマウスの大脳皮質ニューロンへ導入したところ、神経細胞死が認められた。

Research Progress Status

29年度が最終年度であるため、記入しない。

Strategy for Future Research Activity

29年度が最終年度であるため、記入しない。

Research Products

• [Journal Article] Modulatory effects of perineuronal oligodendrocytes on neuronal activity in the rat hippocampus (2018)
  • Author(s): Yamazaki Y, Hozumi Y, Kaneko K, Fujii S
  • Journal Title: Neurochemical Research Volume: 43 Pages: 18-31
  • DOI: 10.1007/s11064-017-2278-9
  • Peer Reviewed
• [Journal Article] Strong sonic hedgehog signaling in the mouse ventral spinal cord is not required for oligodendrocyte precursor cell (OPC) generation but is necessary for correct timing of its generation (2017)
  • Author(s): Hashimoto H, Jiang W, Yoshimura T, Moon KH, Bok J, Ikenaka K
  • Journal Title: Neurochem Int Volume: 印刷中 Pages: -
  • DOI: 10.1016/j.neuint.2017.11.003
  • Peer Reviewed
• [Journal Article] Sulfatase2 modulates fate change from motor neurons to oligodendrocyte precursor cells through coordinated regulation of Shh signaling with sulfatase1 (2017)
  • Author(s): Jiang W, Ishino Y, Hashimoto H, Keino-Masu K, Masu M, Uchimura K, Kadomatsu K, Yoshimura T, Ikenaka K
  • Journal Title: Dev Neurosci Volume: 39(5) Pages: 361-374
  • DOI: 10.1159/000464284
  • Peer Reviewed
• [Journal Article] The balance between cathepsin C and cystatin F controls remyelination in the brain of Plp1-overexpressing mouse, a chronic demyelinating disease model (2017)
  • Author(s): Shimizu T, Wisessmith W, Li J, Abe M, Sakimura K, Chetsawang B, Sahara Y, Tohyama K, Tanaka KF, Ikenaka K
  • Journal Title: GLIA Volume: 65(6) Pages: 917-930
  • DOI: 10.1002/glia.23134
  • Peer Reviewed
• [Journal Article] GlcNAc6ST-1 regulates sulfation of N-glycans and myelination in the peripheral nervous system (2017)
  • Author(s): Yoshimura T, Hayashi A, Handa-Narumi M, Yagi H, Ohno N, Koike T, Yamaguchi Y, Uchimura K, Kadomatsu K, Sedzik J, Kitamura K, Kato K, Trapp BD, Baba H, Ikenaka K
  • Journal Title: Sci Rep Volume: 7 Pages: 42257-42257
  • DOI: 10.1038/srep42257
  • Peer Reviewed / Open Access
• [Journal Article] YAP functions as a mechanotransducer in oligodendrocyte morphogenesis and maturation (2017)
  • Author(s): Shimizu T, Osanai Y, Tanaka KF, Abe M, Natsume R, Sakimura K, Ikenaka K
  • Journal Title: GLIA Volume: 65(2) Pages: 360-374
  • DOI: 10.1002/glia.23096
  • Peer Reviewed
• [Journal Article] Astrocyte-Mediated Infantile-Onset Leukoencephalopathy Mouse Model (2017)
  • Author(s): Sugio S, Tohyama K, Oku S, Fujiyoshi K, Yoshimura T, Hikishima K, Yano R, Fukuda T, Nakamura M, Okano H, Watanabe M, Fukata M, Ikenaka K, Tanaka KF
  • Journal Title: GLIA Volume: 65(1) Pages: 150-168
  • DOI: 10.1002/glia.23084
  • Peer Reviewed
• [Journal Article] Rabies virus-mediated oligodendrocyte labeling reveals a singleoligodendrocyte myelinates axons from distinct brain regions (2017)
  • Author(s): Osanai Y, Shimizu T, Mori T, Yoshimura Y, Hatanaka N, Nambu A, Kimori Y, Koyama S, Kobayashi K, Ikenaka K
  • Journal Title: GLIA Volume: 65(1) Pages: 93-105
  • DOI: 10.1002/glia.23076
  • Peer Reviewed
• [Journal Article] Maturation of Cerebellar Purkinje Cell Population Activity during Postnatal Refinement of Climbing Fiber Network (2017)
  • Author(s): Good JM, Mahoney M, Miyazaki T, Tanaka KF, Sakimura K, Watanabe M, Kitamura K, Kano M
  • Journal Title: Cell Rep Volume: 21(8) Pages: 2066-2073
  • DOI: 10.1016/j.celrep.2017.10.101
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Abrogated Freud-1/Cc2d1a Repression of 5-HT1A Autoreceptors Induces Fluoxetine-Resistant Anxiety/Depression-Like Behavior (2017)
  • Author(s): Vahid-Ansari F, Daigle M, Manzini MC, Tanaka KF, Hen R, Geddes SD, Beique JC, James J, Merali Z, Albert PR
  • Journal Title: J Neurosci Volume: 37(49) Pages: 11967-11978
  • DOI: 10.1523/JNEUROSCI.1668-17.2017
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Time-controllable Nkcc1 knockdown replicates reversible hearing loss in postnatal mice (2017)
  • Author(s): Watabe T, Xu M, Watanabe M, Nabekura J, Higuchi T, Hori K, Sato MP, Nin F, Hibino H, Ogawa K, Masuda M, Tanaka KF
  • Journal Title: Sci Rep Volume: 7(1) Pages: 13605
  • DOI: 10.1038/s41598-017-13997-7
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Quantitative temporal changes in DTI values coupled with histological properties in cuprizone-induced demyelination and remyelination. (2017)
  • Author(s): Yano R, Hata J, Abe Y, Seki F, Yoshida K, Komaki Y, Okano H, Tanaka KF
  • Journal Title: Neurochem Int Volume: - Pages: -
  • DOI: 10.1016/j.neuint.2017.10.004
  • Peer Reviewed
• [Journal Article] Hearing Loss Controlled by Optogenetic Stimulation of Nonexcitable Nonglial Cells in the Cochlea of the Inner Ear (2017)
  • Author(s): Sato MP, Higuchi T, Nin F, Ogata G, Sawamura S, Yoshida T, Ota T, Hori K, Komune S, Uetsuka S, Choi S, Masuda M, Watabe T, Kanzaki S, Ogawa K, Inohara H, Sakamoto S, Takebayashi H, Doi K, Tanaka KF, Hibino H
  • Journal Title: Front Mol Neurosci Volume: 10 Pages: 300
  • DOI: 10.3389/fnmol.2017.00300
  • Peer Reviewed / Open Access
• [Journal Article] Distinct roles of ventrome versus ventrolateral striatal medium spiny neurons in reward-oriented behavior (2017)
  • Author(s): Tsutsui-Kimura I, Natsubori A, Mori M, Kobayashi K, Drew MR, de Kerchove d'Exaerde A, Mimura M, *Tanaka KF
  • Journal Title: Current Biology Volume: 27(19) Pages: 3042-3048
  • DOI: 10.1016/j.cub.2017.08.061
  • Peer Reviewed
• [Journal Article] Mitochondrial DNA double-strand breaks in oligodendrocytes cause demyelination, axonal injury and CNS inflammation (2017)
  • Author(s): Madsen P, Pinto M, Patel S, McCarthy S, Gao H, Taherian M, Karmally S, Pereira C, Dvoriantchikova G, Ivanov D, Tanaka KF, Moraes C, Brambilla R
  • Journal Title: J Neurosci Volume: 37(42) Pages: 10185-10199
  • DOI: 10.1523/JNEUROSCI.1378-17.2017
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Serotonin hormonally regulates lacrimal gland secretory function via the serotonin type 3a receptor (2017)
  • Author(s): Imada T, *Nakamura S, Hisamura R, Izuta Y, Jin K, Ito M, Kitamura N, Tanaka KF, Shibuya I, Tsubota K.Shibuya I, Tsubota K
  • Journal Title: Sci Rep Volume: 7(1) Pages: 6965
  • DOI: 10.1038/s41598-017-06022-4
  • Peer Reviewed / Open Access
• [Journal Article] High-Speed and Scalable Whole-Brain Imaging in Rodents and Primates (2017)
  • Author(s): Seiriki K, Kasai A, Hashimoto T, Schulze W, Niu M, Yamaguchi S, Nakazawa T, Inoue KI, Uezono S, Takada M, Naka Y, Igarashi H, Tanuma M, Waschek JA, Ago Y, Tanaka KF, Hayata-Takano A, Nagayasu K, Shintani N, Hashimoto R, Kunii Y, Hino M, Matsumoto J, Yabe H, Nagai T, Fujita K, Matsuda T, Takuma K, Baba A, Hashimoto H
  • Journal Title: Neuron Volume: 94(6) Pages: 1085-1100
  • DOI: 10.1016/j.neuron.2017.05.017
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Association of impaired neuronal migration with cognitive deficits in extremely preterm infants (2017)
  • Author(s): Kubo KI, Deguchi K, Nagai T, Ito Y, Yoshida K, Endo T, Benner S, Shan W, Kitazawa A, Aramaki M, Ishii K, Shin M, Matsunaga Y, Hayashi K, Kakeyama M, Tohyama C, Tanaka KF, Tanaka K, Takashima S, Nakayama M, Itoh M, Hirata Y, Antalffy B, Armstrong DD, Yamada K, Inoue K, Nakajima K
  • Journal Title: JCI Insight Volume: 2(10) Pages: 88609
  • DOI: 10.1172/jci.insight.88609
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] OCD candidate gene SLC1A1/EAAT3 impacts basal ganglia-mediated activity and stereotypic behavior (2017)
  • Author(s): Zike ID, Chohan MO, Kopelman JM, Krasnow EN, Flicker D, Nautiyal KM, Bubser M, Kellendonk C, Jones CK, Stanwood G, Tanaka KF, Moore H, Ahmari SE, Veenstra-VanderWeele J
  • Journal Title: Proc Natl Acad Sci U S A Volume: 114(22) Pages: 5719-5724
  • DOI: 10.1073/pnas.1701736114
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] A new paradigm for evaluating avoidance/escape motivation. (2017)
  • Author(s): Tsutsui-Kimura I, Bouchekioua Y, Mimura M, Tanaka KF.
  • Journal Title: Int J Neuropsychopharmacol Volume: 20(7) Pages: 593-601
  • DOI: 10.1038/ncomms14304
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Ventrolateral Striatal Medium Spiny Neurons Positively Regulate Food-Incentive, Goal-Directed Behavior Independently of D1 and D2 Selectivity (2017)
  • Author(s): Natsubori A, Tsutsui-Kimura I, Nishida H, Bouchekioua Y, Sekiya H, Uchigashima M, Watanabe M, de Kerchove d'Exaerde A, Mimura M, Takata N, Tanaka KF
  • Journal Title: J Neurosci Volume: 37(10) Pages: 2723-2733
  • DOI: 10.1523/JNEUROSCI.3377-16.2017
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Dysfunction of ventrolateral striatal dopamine receptor type 2-expressing medium spiny neurons impairs instrumental motivation (2017)
  • Author(s): Tsutsui-Kimura I, Takiue H, Yoshida K, Xu M, Yano R, Ohta H, Nishida H, Bouchekioua Y, Okano H, Uchigashima M, Watanabe M, Takata N, Drew MR, Sano H, Mimura M, Tanaka KF
  • Journal Title: Nat Communications Volume: 8 Pages: 14304
  • DOI: 10.1038/ncomms14304
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] 強迫症研究のこれからtranslational researchの可能性について (2017)
  • Author(s): 酒井 雄希, 田中 謙二
  • Journal Title: 精神科治療学 Volume: 32(3) Pages: 399-404
• [Journal Article] Reactive astrocytes function as phagocytes after brain ischemia via ABCA1-mediated pathway (2017)
  • Author(s): Morizawa YM, Hirayama Y, Ohno N, Shibata S, Shigetomi E, Sui Y, Nabekura J, Sato K, Okajima F, Takebayashi H, Okano H, Koizumi S.
  • Journal Title: Nature Comm Volume: 8(1) Pages: 28
  • DOI: 10.1038/s41467-017-00037-1
  • Peer Reviewed / Open Access
• [Presentation] Mechanism that arrests myelin regeneration in chronic demyelinated lesions (2018)
  • Author(s): 池中一裕
  • Organizer: 第8回 新潟大学脳研研究所共同研究拠点国際シンポジウム
  • Invited
• [Presentation] 意欲行動の開始を支配する島皮質-線条体回路 (2017)
  • Author(s): 田中謙二
  • Organizer: 次世代脳 新学術領域合同シンポジウム
  • Invited
• [Presentation] Fiberphotometry (2017)
  • Author(s): 田中謙二
  • Organizer: 第28回 マイクロダイアリシス研究会
  • Invited
• [Presentation] DGK‐εノックアウトマウスを用いた行動解析 (2017)
  • Author(s): 多田裕治, 松本翔平, 水野綱紀, 武内健太朗, 田﨑太一, 藤原浩樹, 後藤薫, 藤井聡
  • Organizer: 山形大学医学部実験動物セミナー・第28回研究成果発表会
• [Presentation] シナプス可塑性の刺激パターンの依存性 (2017)
  • Author(s): 藤井聡, 山崎良彦, 後藤純一, 藤原浩樹
  • Organizer: 第34回山形電気生理研究会
• [Presentation] 結節硬化症原因遺伝子欠損マウスにおけるシナプス可塑性異常の改善に向けたアプローチ (2017)
  • Author(s): 後藤純一, 山形要人, 島田忠之, 藤原浩樹, 山崎良彦, 藤井聡
  • Organizer: 第34回山形電気生理研究会
• [Presentation] 海馬シナプス可塑性の刺激パターン依存性 (2017)
  • Author(s): 藤井聡, 山崎良彦, 後藤純一, 藤原浩樹
  • Organizer: 第49回東北生理談話会
• [Presentation] 光操作・光計測 (2017)
  • Author(s): 田中謙二
  • Organizer: 第４９回藤田学園医学会・研究最前線セミナー
  • Invited
• [Presentation] 島皮質-線条体回路と意欲行動 (2017)
  • Author(s): 田中謙二
  • Organizer: 第5回心身医学のニューロサイエンス研究会
  • Invited
• [Presentation] Oligodendrocyte is a dynamic modulator of conduction velocity (2017)
  • Author(s): 田中謙二、山崎良彦
  • Organizer: 第60回 日本神経化学会
• [Presentation] 光観察と光操作を組み合わせた意欲行動研究 (2017)
  • Author(s): 田中謙二
  • Organizer: 第2回 ルミノジェネティクス研究会
  • Invited
• [Presentation] Exploring the factors causing remyelination arrest through studying cystatin F gene expression regulatory mechanism (2017)
  • Author(s): Jiayi Li
  • Organizer: 13th Biennial ISN Satellite Metting Myelin Biology 2017 Glial Neuronal Interactions
  • Int'l Joint Research
• [Presentation] Origodendrocytes myelinate axons by sensing neuronal subtypes and/or sensory inputs with individual variance in selectivity (2017)
  • Author(s): Kazuhiro Ikenaka
  • Organizer: 13th Biennial ISN Satellite Metting Myelin Biology 2017 Glial Neuronal Interactions
  • Int'l Joint Research / Invited
• [Presentation] Exploring the factors causing remyelination arrest through studying cystatin F gene expression regulatory mechanism (2017)
  • Author(s): Jiayi Li
  • Organizer: ISN-ESN Meeting
  • Int'l Joint Research
• [Presentation] Exploring the factors causing remyelination arrest through studying cystatin F gene expression regulatory mechanism (2017)
  • Author(s): Jiayi Li
  • Organizer: 第40回日本神経科学大会
• [Presentation] Analysis of neuronal resposes against disruption of paranodal junction (2017)
  • Author(s): 池中一裕
  • Organizer: 第40回日本神経科学大会
• [Presentation] Functional analysis of Rho/Rho-kinase signaling pathway in corticostriatal neuron survival using a new gene delivery system (2017)
  • Author(s): 小林憲太
  • Organizer: 第40回日本神経科学大会