Can glia modify the neuronal activities-proving "tripartite synapse theory"-

• Project/Area Number: 15K14354
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Neurochemistry/Neuropharmacology
• Research Institution: Nara Medical University
• Principal Investigator: Wanaka Akio 奈良県立医科大学, 医学部, 教授 (90210989)
• Co-Investigator(Kenkyū-buntansha): 奥田 洋明 金沢大学, 医学系, 准教授 (40453162) ; 森田 晶子 奈良県立医科大学, 医学部, 助教 (70647049)
• Co-Investigator(Renkei-kenkyūsha): NAMBU Atsushi 生理学研究所, システム脳科学研究領域, 教授 (80180553)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: アストロサイト / 三つ組みシナプス / GFAP / Olig2 / DREADD法 / 自発運動 / 淡蒼球 / シナプス / 微細突起 / 運動 / 光遺伝学 / ウイルスベクター / 電子顕微鏡 / 微細構造 / 突起

Outline of Final Research Achievements

Astrocytes are known to form "Tripartite synapse" with pre-and post synaptic neuronal elements. The question we would like to address in the present study is "Does modification of astrocytic functions influence neuronal activity?" To this end, we checked ultrastructures of astrocytes before and after three-week voluntary exercise. After exercise, the fine processes of astrocytes increased their complexities, suggesting that astrocytes responded to increased neuronal activities. During this morphological study, we noticed that in the Globus Pallidus there are two distinct populations of astrocytes, one is Olig2-expressing astrocytes and another is GFAP-expressing astrocytes. These two populations distributed in a mutually-exclusive manner. We transfected M3Dq receptor, which can activate cells in the presence of designer drug, CNO (DREADD method). Using this method, we activated astrocytes in the Globus Pallidus and the mice were less active as compared to the control mice.

Research Products

• [Journal Article] Propofol induces nuclear localization of Nrf2 under conditions of oxidative stress in cardiac H9c2 cells (2018)
  • Author(s): Shinjo Takeaki、Tanaka Tatsuhide、Okuda Hiroaki、Kawaguchi Akira T.、Oh-hashi Kentaro、Terada Yuki、Isonishi Ayami、Morita-Takemura Shoko、Tatsumi Kouko、Kawaguchi Masahiko、Wanaka Akio
  • Journal Title: PLOS ONE Volume: 13 Issue: 4 Pages: e0196191-e0196191
  • DOI: 10.1371/journal.pone.0196191
  • Peer Reviewed / Open Access
• [Journal Article] Olig2-Lineage Astrocytes: A Distinct Subtype of Astrocytes That Differs from GFAP Astrocytes (2018)
  • Author(s): Tatsumi Kouko、Isonishi Ayami、Yamasaki Miwako、Kawabe Yoshie、Morita-Takemura Shoko、Nakahara Kazuki、Terada Yuki、Shinjo Takeaki、Okuda Hiroaki、Tanaka Tatsuhide、Wanaka Akio
  • Journal Title: Front. Neuroanat. Volume: 12 Pages: 1-17
  • DOI: 10.3389/fnana.2018.00008
  • Peer Reviewed / Open Access
• [Journal Article] Effects of cross-rearing with social peers on myelination in the medial prefrontal cortex of a mouse model with autism spectrum disorder (2017)
  • Author(s): Makinodan M. Okumura K. Ikawa D. Yamashita Y. Yamamuro K. Toritsuka M. Kimoto S. Yamauchi T. Komori T. Kayashima Y. Yoshino H. Wanaka A. Kishimoto T.
  • Journal Title: Heliyon Volume: 3 Issue: 11 Pages: e00468-e00468
  • DOI: 10.1016/j.heliyon.2017.e00468
  • Peer Reviewed / Open Access
• [Journal Article] Effects of the mode of re-socialization after juvenile social isolation on medial prefrontal cortex myelination and function (2017)
  • Author(s): Makinodan M. Ikawa D. Yamamuro K. Yamashita Y. Torituka M. Kimoto S. Okumura K. Komori T. Fukami S. Yoshino H. Kanba S. Wanaka A. Kishimoto T
  • Journal Title: Sci.Rep Volume: 14 Issue: 1 Pages: 5481-5481
  • DOI: 10.1038/s41598-017-05632-2
  • Peer Reviewed / Open Access
• [Journal Article] Efficient induction of inner ear hair cell-like cells from mouse ES cells using combination of Math1 transfection and conditioned medium from ST2 stromal cells. (2017)
  • Author(s): Ouji Y, Sakagami M, Omori H, Higashiyama S, Kawai N, Kitahara T, Wanaka A, Yoshikawa M.
  • Journal Title: Stem Cell Research Volume: 23 Pages: 50-56
  • DOI: 10.1016/j.scr.2017.06.013
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Regulation and/or repression of cholinergic differentiation of murine embryonic stem cells using RNAi directed against transcription factor L3/Lhx8. (2017)
  • Author(s): Manabe T, Wanaka A.
  • Journal Title: Methods Molecular Biology Volume: 1622 Pages: 101-109
  • DOI: 10.1007/978-1-4939-7108-4_8
  • ISBN: 9781493971060, 9781493971084
  • Peer Reviewed
• [Journal Article] Effects of Canon chord progression on brain activity and motivation are dependent on subjective feelings, not the chord progression per se (2017)
  • Author(s): Kayashima Yoshinori、Yamamuro Kazuhiko、Makinodan Manabu、Nakanishi Yoko、Wanaka Akio、Kishimoto Toshifumi
  • Journal Title: Neuropsychiatric Disease and Treatment Volume: Volume 13 Pages: 1499-1508
  • DOI: 10.2147/ndt.s136815
  • Peer Reviewed
• [Journal Article] Microglia support ATF3-positive neurons following hypoglossal nerve axotomy. (2017)
  • Author(s): Tanaka T, Murakami K, Bando Y, Nomura T, Isonishi A, Morita-Takemura S, Tatsumi K, Wanaka A, Yoshida S.
  • Journal Title: Neurochemistry International Volume: 印刷中 Pages: 332-342
  • DOI: 10.1016/j.neuint.2017.05.007
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Microglia-derived neuregulin expression in psychiatric disorders. (2017)
  • Author(s): Ikawa D, Makinodan M, Iwata K, Ohgidani M, Kato TA, Yamashita Y, Yamamuro K, Kimoto S, Toritsuka M, Yamauchi T, Fukami SI, Yoshino H, Okumura K, Tanaka T, Wanaka A, Owada Y, Tsujii M, Sugiyama T, Tsuchiya K, Mori N, Hashimoto R, Matsuzaki H, Kanba S, Kishimoto T.
  • Journal Title: Brain Behav Immun. Volume: 61 Pages: 375-385
  • DOI: 10.1016/j.bbi.2017.01.003
  • Peer Reviewed / Open Access
• [Journal Article] Hedgehog Signaling Components Are Expressed in Choroidal Neovascularization in Laser-induced Retinal Lesion (2016)
  • Author(s): Nochioka K, Okuda H, Tatsumi K, Morita S, Ogata N, Wanaka A.
  • Journal Title: ACTA HISTOCHEMICA ET CYTOCHEMICA Volume: 49 Issue: 2 Pages: 67-74
  • DOI: 10.1267/ahc.15036
  • NAID: 130005149556
  • ISSN: 0044-5991, 1347-5800
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Voluntary Exercise Induces Astrocytic Structural Plasticity in the Globus Pallidus. (2016)
  • Author(s): Tatsumi K, Okuda H, Morita-Takemura S, Tanaka T, Isonishi A, Shinjo T, Terada Y, Wanaka A.
  • Journal Title: Front Cell Neurosci. Volume: 10 Pages: 165-165
  • DOI: 10.3389/fncel.2016.00165
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] A subtype of olfactory bulb interneurons is required for odor detection and discrimination behaviors (2016)
  • Author(s): Takahashi H, Ogawa Y, Yoshihara S, Asahina R, Kinoshita M, Kitano T, Kitsuki M, Tatsumi K, Okuda M, Tatsumi K, Wanaka A, Hirai H, Stern PL and Tsuboi A
  • Journal Title: The Journal of Neuroscience Volume: 36 Issue: 31 Pages: 8210-8227
  • DOI: 10.1523/jneurosci.2783-15.2016
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Changes in endothelial cell proliferation and vascular permeability after systemic lipopolysaccharide administration in the subfornical organ. (2016)
  • Author(s): Morita-Takemura S, Nakahara K, Tatsumi K, Okuda H, Tanaka T, Isonishi A, Wanaka A.
  • Journal Title: J Neuroimmunol. Volume: 298 Pages: 132-137
  • DOI: 10.1016/j.jneuroim.2016.06.011
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Social isolation impairs remyelination in mice through modulation of IL-6. (2016)
  • Author(s): Makinodan M, Ikawa D, Miyamoto Y, Yamauchi J, Yamamuro K, Yamashita Y, Toritsuka M, Kimoto S, Okumura K, Yamauchi T, Fukami SI, Yoshino H, Wanaka A, Kishimoto T.
  • Journal Title: FASEB J. Volume: 30 Pages: 4267-4274
  • Peer Reviewed
• [Journal Article] Heterogenous vascular permeability and alternative diffusion barrier in the sensory circumventricular organs of adult mouse brain (2015)
  • Author(s): Morita, S, Furube, E, Mannari, T, Okuda, H, Tatsumi, K, Wanaka, A, Miyata, S
  • Journal Title: Cell and Tissue Research Volume: 0 Issue: 2 Pages: 0-0
  • DOI: 10.1007/s00441-015-2207-7
  • Peer Reviewed / Open Access
• [Journal Article] Hedgehog Signaling Modulates the Release of Gliotransmitters from Cultured Cerebellar Astrocytes. (2015)
  • Author(s): Okuda H, Tatsumi K, Morita-Takemura S, Nakahara K, Nochioka K, Shinjo T, Terada Y, Wanaka A
  • Journal Title: Neurochem Res Volume: 41 Issue: 1-2 Pages: 278-89
  • DOI: 10.1007/s11064-015-1791-y
  • Peer Reviewed
• [Journal Article] Retinoic acid regulates Lhx8 expression via FGF-8b to the upper jaw development of chick embryo (2015)
  • Author(s): Shimomura T, Kawakami M, Okuda H,Tatsumi K, Morita S, Nochioka K, Kirita T, Wanaka A.
  • Journal Title: Journal of Bioscience and Bioengineering Volume: 119 Issue: 3 Pages: 260-266
  • DOI: 10.1016/j.jbiosc.2014.08.010
  • NAID: 110009923564
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Vascular endothelial growth factor-dependent angiogenesis and dynamic vascular plasticity in the sensory circumventricular organs of adult mouse brain (2015)
  • Author(s): Morita, S, Furube, E, Mannari, T, Okuda, H, Tatsumi, K, Wanaka, A, Miyata, S
  • Journal Title: Cell and Tissue Research Volume: 359 Issue: 3 Pages: 865-884
  • DOI: 10.1007/s00441-014-2080-9
  • Peer Reviewed
• [Journal Article] Astrocytic TLR4 expression and LPS-induced nuclear translocation of STAT3 in the sensory circumventricular organs of adult mouse brain (2015)
  • Author(s): Nakano, Y, Furube, E, Morita, S, Wanaka, A, Nakashima, T, Miyata, S
  • Journal Title: Journal of Neuroimmunology Volume: 278 Pages: 144-158
  • DOI: 10.1016/j.jneuroim.2014.12.013
  • Peer Reviewed
• [Presentation] 脳弓下器官のIL-1β産生における血管周囲マクロファージ様細胞の役割 (2018)
  • Author(s): 森田ー竹村晶子、中原一貴、長谷川ー石井さなえ、石西綾美、辰巳晃子、奥田洋明、田中達英、和中明生
  • Organizer: 第123回日本解剖学会総会（武蔵野市）
• [Presentation] FACS解析による成熟脳に存在するOlig2系譜アストロサイトの分離 (2018)
  • Author(s): 辰巳晃子、石西綾美、河邉良枝、森田ー竹村晶子、中原一貴、田中達英、和中明生
  • Organizer: 第123回日本解剖学会総会（武蔵野市）
• [Presentation] Multiplex staining法を用いた脳梁内数珠状グリア細胞の免疫組織化学的解析 (2018)
  • Author(s): 河邉良枝、田中達英、石西綾美、森田ー竹村晶子、中原一貴、辰巳晃子、和中明生
  • Organizer: 第123回日本解剖学会総会（武蔵野市）
• [Presentation] 運動神経損傷後の神経細胞体周囲に集積するミクログリアの機能 (2017)
  • Author(s): 田中達英
  • Organizer: 第122回日本解剖学会総会（長崎市）
• [Presentation] 弓状核及び正中隆起における血中物質の到達と血管構築変化 (2017)
  • Author(s): 森田ー竹村晶子
  • Organizer: 第122回日本解剖学会総会（長崎市）
• [Presentation] Olig2-lineage astrocytes comprises a subpopulation of astrocytes distinct from GFAP-positive ones in the adult mouse brain. (2017)
  • Author(s): Kouko Tatsumi，Ayami Isonishi，Shoko Morita-Takemura，Tatsuhide Tanaka，Akio Wanaka
  • Organizer: 第６0回日本神経化学会大会（仙台市）
• [Presentation] Microglia support ATF3-positive neurons following hypoglossal nerve axotomy (2017)
  • Author(s): Tatsuhide Tanaka1，Koichi Murakami2，Yoshio Bando2，Taichi Nomura2，Ayami Isonishi1，Shoko Morita-Takemura1，Kouko Tatsumi1，Akio Wanaka1，Shigetaka Yoshida2
  • Organizer: 第６0回日本神経化学会大会（仙台市）
• [Presentation] Astrocytic structural changes correlate with overall running activities in the globus pallidus (2016)
  • Author(s): Tatsumi K, Okuda H, Takemura SM, Tanaka T, Isonishi A, Wanaka A
  • Organizer: 第14回 アジア太平洋神経化学会議
  • Place of Presentation: マレーシア、クアラルンプール
  • Year and Date: 2016-08-27
  • Int'l Joint Research
• [Presentation] Hedgehog signaling modulates the release of gliotransmitters from cultured cerebellar astrocytes. (2015)
  • Author(s): 奥田洋明、辰巳晃子、森田晶子、和中明生
  • Organizer: 第58回日本神経化学会大会
  • Place of Presentation: 大宮ソニックシティ
  • Year and Date: 2015-09-11
• [Presentation] Characterization of Olig2 positive astrocytes in the normal adult forebrain (2015)
  • Author(s): 辰巳晃子、奥田洋明、森田晶子、和中明生
  • Organizer: 第58回日本神経化学会大会
  • Place of Presentation: 大宮ソニックシティ
  • Year and Date: 2015-09-11
• [Presentation] Astrocytic chondroitin sulfate proteoglycan in brain injury and in glutamate uptake functions (2015)
  • Author(s): Akio Wanaka, Hiroaki Okuda, Kouko Tatsumi, Shoko Morita
  • Organizer: 25th Meeting of the International Society for Neurochemistry
  • Place of Presentation: Cairns, Australia
  • Year and Date: 2015-08-23
  • Int'l Joint Research
• [Presentation] 末梢からの炎症シグナルによって引き起こされる脳弓下期間の血管の可塑的変化 (2015)
  • Author(s): 森田晶子、中原一貴、辰巳晃子、奥田洋明、宮田清司、和中明生
  • Organizer: 第38回日本神経科学大会
  • Place of Presentation: 神戸国際会議場
  • Year and Date: 2015-07-28