Formation of signaling complex in P2Y12 receptor-mediated microglial chemotaxis.

• Project/Area Number: 21790080
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Biological pharmacy
• Research Institution: Kyushu University
• Principal Investigator: SAITOH Hidetoshi Kyushu University, 薬学研究院, 助教 (90444794)
• Project Period (FY): 2009 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2010: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2009: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 神経生物学 / ATP受容体 / ミクログリア / 神経科学 / イメージング / 脂質ラフト

Research Abstract

This study established a method which achieved effective transgene expression in primary microglia from neonatal rat forebrain using lentiviral vectors possessing iba1 promoter and transgenes. In addition, this study revealed that two chemokine, CCL2 and CCL3, are upregulated by activation of P2Y12 receptor in primary microglia.

Research Products

• [Journal Article] Involvement of vasodilator-stimulated phosphoprotein in UDP-induced microglial actin aggregation via PKC- and Rho-dependent pathways (2011)
  • Author(s): Kataoka A, Koga Y, Uesugi A, Tozaki-Saitoh H, Tsuda M, Inoue K
  • Journal Title: Purinergic Signaling in press
• [Journal Article] Astrocytic P2Y(1) receptor is involved in the regulation of cytokine/chemokine transcription and cerebral damage in a rat model of cerebral ischemia. (2011)
  • Author(s): Kuboyama K, Harada H, Tozaki-Saitoh H, Tsuda M, Ushijima K, Inoue K.
  • Journal Title: J Cereb Blood Flow Metab. in press
• [Journal Article] Neuronal CCL21 up-regulates microglia P2X4 expression and initiates neuropathic pain development. (2011)
  • Author(s): Biber K, Tsuda M, Tozaki-Saitoh H, Tsukamoto K, Toyomitsu E, Masuda T, Boddeke H, Inoue K.
  • Journal Title: EMBO J 30(9) Pages: 73-1864
• [Journal Article] JAK-STAT3 pathway regulates spinal astrocyte proliferation and neuropathic pain maintenance in rats. (2011)
  • Author(s): Tsuda M, Kohro Y, Yano T, Tsujikawa T, Kitano J, Tozaki-Saitoh H, Koyanagi S, Ohdo S, Ji R-R, Salter MW, Inoue K
  • Journal Title: Brain 134 Pages: 39-1127
• [Journal Article] JAK-STAT3 pathway regulates spinal astrocyte proliferation and neuropathic pain maintenance in rats. (2011)
  • Author(s): Tsuda M, (他10名)
  • Journal Title: Brain Volume: (In press)
  • Peer Reviewed
• [Journal Article] Neuronal CCL21 up-regulates microglia P2X4 expression and initiates neuropathic pain development. (2011)
  • Author(s): Biber K, (他7名)
  • Journal Title: EMBO Journal Volume: (In press)
  • Peer Reviewed
• [Journal Article] Purinergic regulation of microglia (2010)
  • Author(s): Tozaki-Saitoh H, Tsuda M, Inoue K
  • Journal Title: 日本薬理学雑誌 136(2) Pages: 7-93
  • NAID: 10026631861
• [Journal Article] Nerve injury-activated microglia engulf myelinated axons in a P2Y12 signaling-dependent manner in the dorsal horn. (2010)
  • Author(s): Maeda M, Tsuda M, Tozaki-Saitoh H, Inoue K, Kiyama H
  • Journal Title: Glia. 58(15) Pages: 46-1838
• [Journal Article] Pain and purinergic signaling. (2010)
  • Author(s): Tsuda M, Tozaki-Saitoh H, Inoue K
  • Journal Title: Brain Res Rev. 63(1-2) Pages: 32-222
• [Journal Article] P2X7 receptor activation induces CXCL2 production in microglia through NFAT and PKC/MAPK pathways. (2010)
  • Author(s): Shiratori M, Tozaki-Saitoh H, Yoshitake M, Tsuda M, Inoue K
  • Journal Title: J Neurochem. 114(3) Pages: 9-810
• [Journal Article] P2X7 receptor activation induces CXCL2 production in microglia through NFAT and PKC/MAPK pathways. (2010)
  • Author(s): Shiratori M, (他4名)
  • Journal Title: Journal of Neurochemistry Volume: 114 Pages: 810-819
  • Peer Reviewed
• [Journal Article] Pain and purinergic signaling. (2010)
  • Author(s): Tsuda M, (他2名)
  • Journal Title: Brain research reviews Volume: 63 Pages: 222-232
  • Peer Reviewed
• [Journal Article] Nerve injury-activated microglia engulf myelinated axons in a P2Y12 signaling-dependent manner in the dorsal horn. (2010)
  • Author(s): Maeda M, (他4名)
  • Journal Title: Glia Volume: 58 Pages: 1838-1846
  • Peer Reviewed
• [Journal Article] Purinergic regulation of microglia (2010)
  • Author(s): 齊藤秀俊, (他2名)
  • Journal Title: 日本薬理学雑誌 Volume: 136 Pages: 93-97
  • NAID: 10026631861
  • Peer Reviewed
• [Journal Article] Behavioral phenotypes of mice lacking purinergic P2X4 receptors in acute and chronic pain assays. (2009)
  • Author(s): Tsuda M, Kuboyama K, Inoue T, Nagata K, Tozaki-Saitoh H, Inoue K
  • Journal Title: Mol.Pain;11 5(1) Pages: 28-28
• [Journal Article] Intrathecal delivery of PDGF produces tactile allodynia through its receptors in spinal microglia (2009)
  • Author(s): Masuda J, Tsuda M, Tozaki-Saitoh H, Inoue K
  • Journal Title: Molecular Pain 5 Pages: 23-23
• [Journal Article] Antidepressants inhibit P2X4 receptor function: a possible involvement in neuropathic pain relief. (2009)
  • Author(s): Nagata K, Imai K, Yamashita T, Tozaki-Saitoh H, Tsuda M, Inoue K
  • Journal Title: Mol.Pain,23. 5 Pages: 20-20
• [Journal Article] IFN-{gamma} receptor signaling mediates spinal microglia activation driving neuropathic pain. (2009)
  • Author(s): Tsuda M, Masuda T, Kitano J, Shimoyama H, Tozaki-Saitoh H, Inoue K
  • Journal Title: Proc Natl Acad Sci U S A. 106(19) Pages: 7-8032
• [Journal Article] Mechanisms underlying fibronectin-induced upregulation of P2XR expression in microglia: distinct roles of PI3K-Akt and MEK-ERK signaling pathways. (2009)
  • Author(s): Tsuda M, Toyomitsu E, Kometani M, Tozaki-Saitoh H, Inoue K
  • Journal Title: J Cell Mol Med. 13(9B) Pages: 9-3251
• [Journal Article] P2Y(1) receptor signaling enhances neuroprotection by astrocytes against oxidative stress via IL-6 release in hippocampal cultures. (2009)
  • Author(s): Fujita T, Tozaki-Saitoh H, Inoue K
  • Journal Title: Glia 57(3) Pages: 57-244
• [Presentation] P2Y12 receptors in spinal microglia are required for neuropathic pain after peripheral nerve injury (2011)
  • Author(s): 齊藤秀俊, (他4名)
  • Organizer: 第84回日本薬理学会
  • Place of Presentation: (誌上開催)
  • Year and Date: 2011-03-22
• [Presentation] ミクログリアの貪食時における-過性のカルシウム上昇 (2010)
  • Author(s): 齋藤秀俊
  • Organizer: 第83回日本薬理学会年会
  • Place of Presentation: 大阪国際会議場
  • Year and Date: 2010-03-17
• [Presentation] 神経障害性疼痛発症時の脊髄CCL3の関与 (2010)
  • Author(s): 齊藤秀俊、上田和明、津田誠、井上和秀
  • Organizer: 第83回日本薬理学会年会
  • Place of Presentation: 大阪
• [Presentation] ミクログリアの貪食時における一過性のカルシウム上昇 (2010)
  • Author(s): 齊藤秀俊、津田誠、井上和秀
  • Organizer: 第83回日本薬理学会年会
  • Place of Presentation: 大阪
• [Presentation] P2Y12 receptor in spinal microglia are required for neuropathic pain (2009)
  • Author(s): Tozaki-Saitoh Hidetoshi
  • Organizer: International symposium on Purinergic signalling in New strategy of drug discovery,Joint with JSPS Core-to-Core Program,A satellite symposium for IUPS 2009
  • Place of Presentation: Fukuoka
• [Book] Int Rev Neurobiol 85 (2009)
  • Author(s): Inoue K, Koizumi S, Kataoka A, Tozaki-Saitoh H, Tsuda M
  • Publisher: Chapter 12 P2Y(6)-Evoked Microglial Phagocytosis.
• [Book] 脊髄ミクログリアのP2プリン受容体と神経障害性疼痛、生体の科学「伝達物質と受容体」特集号60 (2009)
  • Author(s): 井上和秀、津田誠、齊藤秀俊
• [Remarks] ホームページ等
  • URL: http://yakkou.phar.kyushu-u.ac.jp/
• [Remarks]
  • URL: http://yakkou.phar.kyushu-u.ac.jp/Publication.html