Mechanisms underlying gliotransmission-mediated neuronal plasticity

2012 Fiscal Year Final Research Report

• Project/Area Number: 21240034
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Neurochemistry/Neuropharmacology
• Research Institution: University of Yamanashi
• Principal Investigator: KOIZUMI Schuichi 山梨大学, 大学院・医学工学総合研究部, 教授 (10280752)
• Co-Investigator(Kenkyū-buntansha): MORIYAMA Yoshinori 岡山大学, 医歯(薬)学総合研究科, 教授 (10150658) ; NAONO Kayoko (藤下 加代子) 山梨大学, 医学工学総合研究部, 助教 (10443102) ; KATAOKA Yasufumi 福岡大学, 薬学部, 教授 (70136513) ; SHINOZAKI Youichi 山梨大学, 医学工学総合研究部, 講師 (10443772) ; SHIGETOMI Eiji 山梨大学, 医学工学総合研究部, 特任助教 (00631061) ; SHIBATA Keisuke 山梨大学, 医学工学総合研究部, 助教 (50580411)
• Project Period (FY): 2009 – 2012
• Keywords: グリア細胞

Research Abstract

Although glia are non-excitable cells, they release gliotransmitter such as ATP, and could regulate various brain functions. However, mechanisms underlying glial ATP release had remained unknown. Here we found that glia release ATP by exocytosis, for which vesicular nucleotide transporter (VNUT) has an essential role. The VNUT-dependent exocytosis was especially important in cases of various brain diseases. Taken together, glial cells control various brain functions by the VNUT-dependent ATP exocytosis.

Research Products

• [Journal Article] In vitro blood-brain barrier models using brain microvascular endothelial cells isolated from infant and adult rats retain age-related phenotypes in the bariier properties (2013)
  • Author(s): Takata, F., Dohgu, S., Yamauchi, A., Matsumoto, J., Machida, T., Fujishita, K., Shibata, K., Shinozaki, Y., Sato, K., Kataoka, Y. and Koizumi, S
  • Journal Title: PLoS One Volume: (in press)
  • Peer Reviewed
• [Journal Article] Purinergic receptors in microglia -Functional modal shift of microglia mediated by P1 and P2 receptors- (2013)
  • Author(s): Koizumi, S., Ohsawa, K., Inoue, K. and Kohsaka, S
  • Journal Title: Glia Volume: 61 Pages: 47-54
  • Peer Reviewed
• [Journal Article] Secreation of matrix metalloproteinase-9 by inhibition of tonic P2Y14-receptor-mediated signal(s) (2013)
  • Author(s): Kinoshita, M., Nasu-Tada, K., Fujishita, K., Sato, K. and Koizumi, S
  • Journal Title: Cellular and Molecular Neurobiology Volume: 33 Pages: 47-53
  • Peer Reviewed
• [Journal Article] Autocrine regulation of macrophage activation via exocytosis of ATP and activation of P2Y11 receptor (2013)
  • Author(s): Sasaki, H., Tsukimoto, M., Harada, H., Moriyama, Y., Koyama, S
  • Journal Title: PROS ONE Volume: 8 Pages: e59778
  • Peer Reviewed
• [Journal Article] The vesicular nucleotide transporter (VNUT) regulates the nucleotide content in airway epithelial mucin granules (2013)
  • Author(s): Sesma, JI., Kreda, SM., Okada, SF., van, Heusden, C., Moussa, L, Jones, LC., O'Neal, WK., Togawa, N., Hiasa, M., Moriyama, Y., Lazarowski, ER
  • Journal Title: Am J Physiol Cell Physiol Volume: (in press)
  • Peer Reviewed
• [Journal Article] Vesicular neurotransmitter transporters: an approach for studying transporters with purified proteins (2013)
  • Author(s): Omote, H., Moriyama, Y
  • Journal Title: Physiology Volume: 28 Pages: 39-50
  • Peer Reviewed
• [Journal Article] Purinergic signaling promotes proliferation of the adult mouse subventricular zone cells (2012)
  • Author(s): Suyama, S., Sunabori, T., Kanki, H., Sawamoto, K., Gachet, C., Koizumi, S. and Okano, H
  • Journal Title: J. Neurosci. Volume: 32 Pages: 9238-9247
  • Peer Reviewed
• [Journal Article] Microscopic visualization of ATP with luciferin-luciferase reaction in mouse skeletal muscles using "in vivo cryotechnique" (2012)
  • Author(s): Terada, N., Saitoh, Y., Saitoh, S., Ohno, N., Fujishita, K., Koizumi, S. and Ohno, S
  • Journal Title: Microscopy and Microanalysis Volume: 15 Pages: 1030-1036
  • Peer Reviewed
• [Journal Article] Cell-autonomous enhancement of glutamate-uptake by female astrocytes (2012)
  • Author(s): Morizawa, Y., Sato, K., Takaki, J., Kawasaki, A., Shibata, K., Suzuki, T., Ohta, S. and Koizumi, S
  • Journal Title: Cell. Mol. Neurobiol Volume: 32 Pages: 953-956
  • Peer Reviewed
• [Journal Article] Severe irritant dermatitis with loss of Langerhans cells in a mouse model of acrodermatitis enteropathica (2012)
  • Author(s): Kawamura, T., Ogawa, Y., Nakamura, Y., Nakamizo, S., Izumi, A., Nakano, H., Kabashima, K., Katayama, I., Koizumi, S., Kodama, T., Nakao, A. and Shinji Shimada
  • Journal Title: J. Clin. Invest. Volume: 122 Pages: 722- 732
  • Peer Reviewed
• [Journal Article] Autocrine regulation of TGF-β1-induced cell migration by exocytosis of ATP and activation of P2 receptors in human lung cancer cells (2012)
  • Author(s): Takai, E., Tsukimoto, M., Harada, H., Sawada, K., Moriyama, Y., Kojima, S
  • Journal Title: J Cell Sci Volume: 125 Pages: 5051-60
  • Peer Reviewed
• [Journal Article] The astrocyte-targeted therapy by Bushi for the neuropathic pain in mice (2011)
  • Author(s): Shibata, K., Sugawara, T., Fujishita, K., Shinozaki, Y., Matsukawa, T., Suzuki, T. and Koizumi, S
  • Journal Title: PLoS One Volume: 6 Pages: e23510
  • Peer Reviewed
• [Journal Article] Divalent cation transport by vesicular nucleotide transporter (2011)
  • Author(s): Miyaji, T., Sawada, K., Omote, H., Moriyama, Y
  • Journal Title: J Biol Chem Volume: 286 Pages: 42881-42887
  • Peer Reviewed
• [Journal Article] Riboflavin transporter is finally identified (2011)
  • Author(s): Moriyama, Y
  • Journal Title: J Biochem Volume: 150 Pages: 341-343
  • Peer Reviewed
• [Journal Article] Functional and Anatomical Identification of a Vesicular Transporter Mediating Neuronal ATP Release (2011)
  • Author(s): Larsson, M., Sawada, K., Morland, C., Hiasa, M., Ormel, L., Moriyama, Y., Gundersen, V
  • Journal Title: Cereb Cortex Volume: (electric version)
  • Peer Reviewed
• [Journal Article] Transient Receptor Potential Vanilloid 4 (TRPV4)-dependent calcium influx and ATP release in mouse esophageal keratinocytes (2011)
  • Author(s): Mihara, H., Boudaka, A., Sugiyama, T., Moriyama Y., Tominaga, M
  • Journal Title: J Physiol Volume: 589(Pt 14) Pages: 3471-82
  • Peer Reviewed
• [Journal Article] Synchronized Ca2+ oscillations in astrocytes (2010)
  • Author(s): Koizumi, S
  • Journal Title: FEBS J Volume: 277 Pages: 286-292
  • Peer Reviewed
• [Journal Article] The TRPV4 cation channel mediates stretch-evoked Ca2+ influx and ATP release in primary urothelial cell cultures (2009)
  • Author(s): Mochizuki, T., Tokabe, T., Araki, I., Fujishita, K., Shibasaki, K., Uchida, K., Naruse, K., Koizumi, S., Takeda, M. and Tominaga, M
  • Journal Title: J. Bio. Chem Volume: 284 Pages: 21257-21264
  • Peer Reviewed
• [Journal Article] Direct observation of ATP-induced conformational changes in single P2X4receptors (2009)
  • Author(s): Shinozaki, Y., Sumitomo, K., Tsuda, M., Koizumi, S., Inoue, K. and Torimitsu, K
  • Journal Title: PLoS Biology Volume: 7 Pages: e103
  • Peer Reviewed
• [Journal Article] Microglia release ATP by exocytosis
  • Author(s): Imura, Y., Morizawa, Y., Komatsu, R., Shibata, K., Shinozaki, Y., Moriyama, Y. and Koizumi S
  • Journal Title: Glia Volume: (in press)
  • Peer Reviewed
• [Presentation] シナプス再編とグリア-ニューロン連関 (2013)
  • Author(s): 小泉修一
  • Organizer: 第86回日本薬理学会年会
  • Place of Presentation: 福岡国際会議場(福岡市)
  • Year and Date: 20130321-23
• [Presentation] Functional modal shift of microglia mediated by astrocytes (2012)
  • Author(s): 小泉修一
  • Organizer: 8th FENS Forum of Neuroscience
  • Place of Presentation: International Convention Center(バルセロナ スペイン)
  • Year and Date: 20120714-18
• [Presentation] Exocytosis ATP and Cellular Functions (2012)
  • Author(s): 小泉修一
  • Organizer: Purine2012
  • Place of Presentation: 福岡
  • Year and Date: 20120531-0602
• [Presentation] Mechanism and Function of Vesicular Nucleotide Transporter (VNUT) (2012)
  • Author(s): 森山芳則
  • Organizer: Purine 2012
  • Place of Presentation: 九州大学(福岡市)
  • Year and Date: 20120531-0602
• [Presentation] Clean biochemical approach により解明された小胞型神経伝達物質トランスポーターの新機能(Structural and functional studies on the vesicular neurotransmitter transporters by clean biochemical approach) (2012)
  • Author(s): 森山芳則
  • Organizer: 第85回日本生化学会大会
  • Place of Presentation: 福岡国際会議場(福岡市)
  • Year and Date: 2012-12-15
• [Presentation] Effects of glial out-put signals on brain function (2012)
  • Author(s): 小泉修一
  • Organizer: GCOE ニューロサイエンス
  • Place of Presentation: 名古屋
  • Year and Date: 2012-10-11
• [Presentation] グリア細胞の情報発信と脳機能 (2012)
  • Author(s): 小泉修一
  • Organizer: 第6回Brain Science Conference
  • Place of Presentation: 京都ブライトンホテル(京都市)
  • Year and Date: 2012-10-06
• [Presentation] Synaptic Effects of Ketones (2012)
  • Author(s): 森山芳則
  • Organizer: (Third International Symposium: Dietary Therapy for Epilepsy & Other Neurological Disorders)
  • Place of Presentation: Hilton Chicago Indian Lakes Resort(シカゴ アメリカ)
  • Year and Date: 2012-09-20
• [Presentation] Mechanisms underlying gliotransmitter ATP and their dysfunctions. (2011)
  • Author(s): Koizumi, S
  • Organizer: The 23rd bennial meeting of international society for Neurochemistry
  • Place of Presentation: Megaron Athens International Conference Centre、(Athens,Greece)
  • Year and Date: 20110828-0902
• [Presentation] Highlighting the Molecular Basis of Purinergic Transmission (2011)
  • Author(s): 森山芳則
  • Organizer: ISN-ESN-2011
  • Place of Presentation: Megaron Athens International Conference Centre(アテネ ギリシャ)
  • Year and Date: 2011-08-29
• [Presentation] Mechanisms underlying upregulation of microglial P2Y6 receptors (2010)
  • Author(s): Koizumi, S
  • Organizer: Society for Neuroscience Meeting. San Diego Convention Center
  • Place of Presentation: (San Diego, USA)
  • Year and Date: 20101114-17
• [Presentation] Cell-to-cell communication mediated by extracellular nucleotides in the CNS (2009)
  • Author(s): Koizumi, S
  • Organizer: A lecture in commemoration of receiving prize "Japan Academy Medal" Fukuoka Purine2009
  • Place of Presentation: ホテル・ザ・ルイガンズ福岡(福岡市)
  • Year and Date: 20090723-25
• [Presentation] Role of vesicular neurotransmitter transpoters in the metabolic reglation (2009)
  • Author(s): 森山芳則
  • Organizer: 第36回国際生理学会生会大会
  • Place of Presentation: 京都国際会館(京都市)
  • Year and Date: 2009-07-29
• [Book] リッピンコットシリーズ イラストレイテッド細胞分子生物学 (2012)
  • Author(s): 森山芳則 水島 昇
  • Total Pages: 141-168
  • Publisher: 丸善出版
• [Patent(Industrial Property Rights)] グリア細胞の活性化抑制組成物 (2012)
  • Inventor(s): 小泉修一、松川隆、藤下加代子、菅原健、柴田圭輔
  • Industrial Property Rights Holder: 国立大学法人山梨大学
  • Industrial Property Number: 特願 2009-267902
  • Filing Date: 2012-11-26
• [Patent(Industrial Property Rights)] ポリアミンの化学伝達を司るトランスポーターの同定とその利用 (2012)
  • Inventor(s): 山芳則・表弘志・宮地孝明・日浅未来
  • Industrial Property Rights Holder: 山芳則・表弘志・宮地孝明・日浅未来
  • Industrial Property Number: 特願 2012-243730
  • Filing Date: 2012-11-05