Role of PDGF signal in normal and injured brain.

2011 Fiscal Year Final Research Report

• Project/Area Number: 20390108
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Experimental pathology
• Research Institution: University of Toyama
• Principal Investigator: SASAHARA Masakiyo 富山大学, 大学院・医学薬学研究部(医学), 教授 (20154015)
• Co-Investigator(Kenkyū-buntansha): MORI Hisashi 富山大学, 大学院・医学薬学研究部(医学), 教授 (00239617) ; ISHII Yoko 富山大学, 大学院・医学薬学研究部(医学), 准教授 (00361949) ; HAMASHIMA Takeru 富山大学, 大学院・医学薬学研究部(医学), 助教 (80467092)
• Co-Investigator(Renkei-kenkyūsha): FUKUNAGA Kohji 東北大学, 大学院・薬学研究科, 教授 (90136721)
• Project Period (FY): 2008 – 2011
• Keywords: 血小板由来増殖因子 / 神経 / 虚血 / 行動 / 血管 / グリア細胞 / 神経幹細胞 / ノックアウトマウス

Research Abstract

We analyzed the conditional knockout model of platelet-derived growth factor receptorβ(PDGFR-β). PDGFR-βpromoted the development of hippocampal pyramidal neurons and GABA neurons, and were involved in the development of cognitive ability and social behavior. PDGFR-βimproved the ischemic brain lesions, and was involved in neuroprotection, maturation of newly-formed blood vessels, the activation of neural stem cells and glial cell reaction. We established double knockout mouse model of PDGFR-αand-βgene for further PDGF research.

Research Products

• [Journal Article] PDGFR-βas a positive regulator of tissue repair in a mouse model of focal cerebral ischemia (2012)
  • Author(s): Shen J, Ishii Y, Xu G, Dang TC, Hamashima T, Matsushima T, Yamamoto S, Hattori Y, Takatsuru Y, Nabekura J, Sasahara M.
  • Journal Title: J Cereb Blood Flow Metab Volume: 32 Pages: 353-367
  • Peer Reviewed
• [Journal Article] Aberrant hippocampal spine morphology and impaired memory formation in neuronal platelet-derived growth factor beta-receptor lacking mice (2012)
  • Author(s): Shioda N, Moriguchi S, Oya T, Ishii Y, Shen J, Matsushima T, Nishijo H, Sasahara M, Fukunaga K.
  • Journal Title: Hippocampus Volume: 22 Pages: 1371-1378
  • Peer Reviewed
• [Journal Article] Platelet-derived growth factor and renal disease (2012)
  • Author(s): Nakagawa T, Inoue H, Sasahara M.
  • Journal Title: Curr Opin Nephrol Hypertens Volume: 21 Pages: 80-85
  • Peer Reviewed
• [Journal Article] Central versus peripheral impact of estradiol on the impaired glucose metabolism in ovariectomized mice on a high-fat diet (2012)
  • Author(s): Yonezawa R, Wada T, Matsumoto N, Morita M, Sawakawa K, Ishii Y, Sasahara M, Tsuneki H, Saito S, Sasaoka T.
  • Journal Title: Am J Physiol Endocrinol Metab
  • DOI: doi:10.1152/ajpendo.00638.2011
  • Peer Reviewed
• [Journal Article] SRT1720, A SIRT1 Activator, Aggravates Bleomycin-Induced Lung Injury in Mice (2012)
  • Author(s): Imanishi S, Hayashi R, Ichikawa T, Suzuki K, Sasahara M, Kondo T, Ogawa H, Tobe K.
  • Journal Title: Food and Nutrition Sciences Volume: 3 Pages: 157-163
  • Peer Reviewed
• [Journal Article] Measuring CREB activation using bioluminescence probes that detect KID-KIX interaction in living cells (2012)
  • Author(s): Ishimoto T, Mano H, Ozawa T, Mori H.
  • Journal Title: Bioconjug Chem Volume: 23 Pages: 923-932
  • Peer Reviewed
• [Journal Article] Role of Serine Racemase in Behavioral Sensitization in Mice after Repeated Administration of Methamphetamine (2012)
  • Author(s): Horio M, Kohno M, Fujita Y, Ishima T, Inoue R, Mori H, Hashimoto K.
  • Journal Title: PLoS ONE Volume: 7 Pages: e35494
  • Peer Reviewed
• [Journal Article] Expression of a truncated form of the endoplasmic reticulum chaperone protein, sigma-1 receptor, promotes mitochondrial energy depletion and apoptosis (2012)
  • Author(s): Shioda N, Ishikawa K, Tagashira H, Ishizuka T, Yawo H, Fukunaga K.
  • Journal Title: J Biol Chem
  • DOI: doi:10.1074/jbc.M112.349142
  • Peer Reviewed
• [Journal Article] Novel dopamine D2 receptor signaling through proteins interacting with the third cytoplasmic loop (2012)
  • Author(s): Fukunaga K, Shioda N.
  • Journal Title: Mol Neurobiol Volume: 45 Pages: 144-152
  • Peer Reviewed
• [Journal Article] Reduced calcium/calmodulin-dependent protein kinase II activity in the hippocampus is associated with impaired cognitive function in MPTP-treated mice (2012)
  • Author(s): Moriguchi S, Yabuki Y, Fukunaga K.
  • Journal Title: J Neurochem Volume: 120 Pages: 541-551
  • Peer Reviewed
• [Journal Article] Targeting nitrosative stress for neurovascular protection : new implications in brain diseases (2012)
  • Author(s): Tao RR, Ji YL, Lu YM, Fukunaga K, Han F.
  • Journal Title: Curr Drug Targets Volume: 13 Pages: 272-284
  • Peer Reviewed
• [Journal Article] PDGF-BB modulates hematopoiesis and tumor angiogenesis by inducing erythropoietin production in stromal cells (2011)
  • Author(s): Xue Y, Lim S, Yang Y, Wang Z, Jensen LD, Hedlund EM, Andersson P, Sasahara M, Larsson O, Galter D, Cao R, Hosaka K, Cao Y.
  • Journal Title: Nat Med Volume: 18 Pages: 100-110
  • Peer Reviewed
• [Journal Article] Deletion of platelet-derived growth factor receptor-βimproves diabetic nephropathy in Ca2+/calmodulin-dependent protein kinase IIα(Thr286Asp) transgenic mice (2011)
  • Author(s): Suzuki H, Usui I, Kato I, Oya T, Kanatani Y, Yamazaki Y, Fujisaka S, Senda S, Ishii Y, Urakaze M, Mahmood A, Takasawa S, Okamoto H, Kobayashi M, Tobe K, Sasahara M.
  • Journal Title: Diabetologia Volume: 54 Pages: 2953-262
  • Peer Reviewed
• [Journal Article] Reduced expression of the ATRX gene, a chromatin-remodeling factor, causes hippocampal dysfunction in mice (2011)
  • Author(s): Nogami T, Beppu H, Tokoro T, Moriguchi S, Shioda N, Fukunaga K, Ohtsuka T, Ishii Y, Sasahara M, Shimada Y, Nishijo H, Li E, Kitajima I.
  • Journal Title: Hippocampus Volume: 21 Pages: 678-687
  • Peer Reviewed
• [Journal Article] Cognitive and Socio-Emotional Deficits in Platelet-Derived Growth Factor Receptor-βGene Knockout Mice (2011)
  • Author(s): Nguyen PT, Nakamura T, Hori E, Urakawa S, Uwano T, Zhao J, Li R, Bac ND, Hamashima T, Ishii Y, Matsushima T, Ono T, Sasahara M, Nishijo H.
  • Journal Title: PLoS One Volume: 6 Pages: e18004
  • Peer Reviewed
• [Journal Article] Roles of PDGF receptor-beta in the structure and function of postnatal kidney glomerulus (2011)
  • Author(s): Nakagawa T, Izumino K, Ishii Y, Oya T, Hamashima T, Jie S, Ishizawa S, Tomoda F, Fujimori T, Nabeshima Y, Inoue H, Sasahara M.
  • Journal Title: Nephrol Dial Transplant Volume: 26 Pages: 458-468
  • Peer Reviewed
• [Journal Article] Levels of D-serine in the brain and peripheral organs of serine racemase(Srr) knock-out mice (2011)
  • Author(s): Horio M, Kohno M, Fujita Y, Ishima T, Inoue R, Mori H, Hashimoto K.
  • Journal Title: Neurochem. Int Volume: 59 Pages: 853-859
  • Peer Reviewed
• [Journal Article] Detection of autoantibody against extracellular epitopes of N-methyl-D-aspartate receptor by cell-based assay (2011)
  • Author(s): Takano S, Takahashi Y, Kishi H, Taguchi Y, Takashima S, Tanaka K, Muraguchi A, Mori H.
  • Journal Title: Neurosci Res Volume: 71 Pages: 294-302
  • Peer Reviewed
• [Journal Article] Heparin-binding EGF-like growth factor is required for synaptic plasticity and memory formation (2011)
  • Author(s): Oyagi A, Moriguchi S, Nitta A, Murata K, Oida Y, Tsuruma K, Shimazawa M, Fukunaga K, Hara H.
  • Journal Title: Brain Res Volume: 1419 Pages: 97-104
  • Peer Reviewed
• [Journal Article] CaMKIIδB mediates aberrant NCX1 expression and the imbalance of NCX1/SERCA in transverse aortic constriction-induced failing heart (2011)
  • Author(s): Lu YM, Huang J, Shioda N, Fukunaga K, Shirasaki Y, Li XM, Han F.
  • Journal Title: PLoS One Volume: 6 Pages: e24724
  • Peer Reviewed
• [Journal Article] Sigma-1 receptor stimulation by dehydroepiandrosterone ameliorates cognitive impairment through activation of CaM kinase II, protein kinase C and extracellular signal-regulated kinase in olfactory bulbectomized mice (2011)
  • Author(s): Moriguchi S, Yamamoto Y, Ikuno T, Fukunaga K.
  • Journal Title: J Neurochem Volume: 117 Pages: 879-891
  • Peer Reviewed
• [Journal Article] Aberrant calcium/calmodulin-dependent protein kinase II(CaMKII) activity is associated with abnormal dendritic spine morphology in the ATRX mutant mouse brain (2011)
  • Author(s): Shioda N, Beppu H, Fukuda T, Li E, Kitajima I, Fukunaga K.
  • Journal Title: J Neurosci Res Volume: 31 Pages: 346-358
  • Peer Reviewed
• [Journal Article] Melatonin ameliorates ischemic-like injury-evoked nitrosative stress : Involvement of HtrA2/PED pathways in endothelial cells (2011)
  • Author(s): Han F, Tao RR, Zhang GS, Lu YM, Liu LL, Chen YX, Lou YJ, Fukunaga K, Hong ZH.
  • Journal Title: J Pineal Res Volume: 50 Pages: 281-291
  • Peer Reviewed
• [Journal Article] Sigma-1 receptor stimulation with fluvoxamine activates Akt-eNOS signaling in the thoracic aorta of ovariectomized rats with abdominal aortic banding (2011)
  • Author(s): Bhuiyan MS, Tagashira H, Fukunaga K.
  • Journal Title: Eur J. Pharmacol Volume: 650 Pages: 621-628
  • Peer Reviewed
• [Journal Article] ATBF1 inhibits estrogen receptor(ER) function by selectively competing with AIB1 for binding to the ER in ER-positive breast cancer cells (2010)
  • Author(s): Dong XY, Sun X, Guo P, Li Q, Sasahara M, Ishii Y, Dong JT.
  • Journal Title: J Biol Chem Volume: 285 Pages: 32801-32809
  • Peer Reviewed
• [Journal Article] Involvement of platelet-derived growth factor-BB and its receptor-beta in hypoxia-induced depression of excitatory synaptic transmission in the nucleus tractus solitarius of mice (2010)
  • Author(s): Ohi Y, Ishii Y, Sasahara M, Haji A.
  • Journal Title: J Pharmacol Sci Volume: 112 Pages: 477-481
  • Peer Reviewed
• [Journal Article] Neuroprotective effects of PDGF against oxidative stress and the signaling pathway involved (2010)
  • Author(s): Zheng L, Ishii Y, Tokunaga A, Hamashima T, Shen J, Zhao QL, Ishizawa S, Fujimori T, Nabeshima Y, Mori H, Kondo T, Sasahara M.
  • Journal Title: J Neurosci Res Volume: 88 Pages: 1273-1284
  • Peer Reviewed
• [Journal Article] Serine racemase knockout mice (2010)
  • Author(s): Mori H, Inoue R.
  • Journal Title: Chem Biodivers Volume: 7 Pages: 1573-1578
  • Peer Reviewed
• [Journal Article] Inhibition of Tpl2 protein kinase suppresses RANKL-induced osteoclastogenesis through down-regulation of the c-Fos and NFATc1 genes (2010)
  • Author(s): Hirata K, Taki H, Shinoda K, Hounoki H, Miyahara T, Tobe K, Ogawa H, Mori H, Sugiyama E.
  • Journal Title: Biol Pharm Bull Volume: 33 Pages: 133-137
  • Peer Reviewed
• [Journal Article] Expression profiling of Ca(2+)/calmodulin-dependent signaling molecules in the rat dorsal and ventral hippocampus after acute lead exposure (2010)
  • Author(s): Zhang GS, Ye WF, Tao RR, Lu YM, Shen GF, Fukunaga K, Huang JY, Ji YL, Han F.
  • Journal Title: Exp Toxicol Pathol
  • DOI: doi:10.1016/j.etp.2010.12.00410.1016/j.etp.2010.12.004
  • Peer Reviewed
• [Journal Article] Activation of MAP kinases, Akt and PDGF receptors in injured peripheral nerves (2009)
  • Author(s): Yamazaki T, Sabit H, Oya T, Ishii Y, Hamashima T, Tokunaga A, Ishizawa S, Jie S, Kurashige Y, Matsushima T, Furuta I, Noguchi M, Sasahara M.
  • Journal Title: J Peripher Nerv Syst Volume: 14 Pages: 165-176
  • Peer Reviewed
• [Journal Article] Hypoxic ventilatory response in platelet-derived growth factor receptor-beta-knockout mice (2009)
  • Author(s): Tsunekawa S, Ohi Y, Ishii Y, Sasahara M, Haji A.
  • Journal Title: J Pharmacol Sci Volume: 110 Pages: 270-275
  • Peer Reviewed
• [Journal Article] Ablation of NMDA receptors enhances the excitability of hippocampal CA3 neurons (2009)
  • Author(s): Fukushima F, Nakao K, Shinoe T, Fukaya M, Muramatsu S-I, Sakimura K, Kataoka H, Mori H, Watanabe M, Manabe T, Mishina M.
  • Journal Title: PLoS ONE Volume: 4 Pages: e3993
  • Peer Reviewed
• [Journal Article] A novel form of memory for auditory fear conditioning at a low-intensity unconditioned stimulus (2009)
  • Author(s): Kishioka A, Fukushima F, Ito T, Kataoka H, Mori H, Ikeda T. Itohara S, Sakimura K, Mishina M.
  • Journal Title: PLoS ONE Volume: 4 Pages: e4157
  • Peer Reviewed
• [Journal Article] PDGF receptor beta is a potent regulator of mesenchymal stromal cell function (2008)
  • Author(s): Tokunaga A, Oya T, Ishii Y, Motomura H, Nakamura C, Ishizawa S, Fujimori T, Nabeshima Y, Umezawa A, Kanamori M, Kimura T, Sasahara M.
  • Journal Title: J Bone Miner Res Volume: 23 Pages: 1519-1528
  • Peer Reviewed
• [Journal Article] Characterization of neuroprogenitor cells expressing the PDGF beta-receptor within the subventricular zone of postnatal mice (2008)
  • Author(s): Ishii Y, Matsumoto Y, Watanabe R, Elmi M, Fujimori T, Nissen J, Cao Y, Nabeshima Y, Sasahara M, Funa K.
  • Journal Title: Mol Cell Neurosci Volume: 37 Pages: 507-518
  • Peer Reviewed
• [Journal Article] NMDA-andβ-amyloid_<1-42>-induced neurotoxicity is attenuated in serine racemase knock-out mice (2008)
  • Author(s): Inoue R, Hashimoto K, Harai T, Mori H.
  • Journal Title: J Neurosci Res Volume: 28 Pages: 14486-14491
  • Peer Reviewed
• [Journal Article] Serine racemase is predominantly localized in neurons in mouse brain (2008)
  • Author(s): Miya K, Inoue R, Takata Y, Abe M, Natsume R, Sakimura K, Hongou K, Miyawaki T, Mori H.
  • Journal Title: J Comp Neurol Volume: 510 Pages: 641-654
  • Peer Reviewed
• [Journal Article] Enhancement of both long-term depression induction and optokinetic response adaptation in mice lacking delphilin (2008)
  • Author(s): Takeuchi T, Ohtsuki G, Yoshida T, Fukaya M, Wainai T, Yamashita M, Yamazaki Y, Mori H, Sakimura K, Kawamoto S, Watanabe M, Hirano T, Mishina M.
  • Journal Title: PLoS ONE Volume: 3 Pages: e2297
• [Journal Article] Effects of FAK ablation on cerebellar foliation, Bergmann glia positioning and climbing fiber territory on Purkinje cells (2008)
  • Author(s): Watanabe F, Miyazaki T, Takeuchi T, Fukaya M, Nomura T, Noguchi S, Mori H, Sakimura K, Watanabe M, Mishina M.
  • Journal Title: Eur J. Neurosci Volume: 27 Pages: 836-854
  • Peer Reviewed
• [Presentation] Neuroprotective Effects of PDGF Against Oxidative Stress and the Signaling Pathway Involved (2011)
  • Author(s): Ishii Y, Zheng L Sasahara M.
  • Organizer: The 6th International conference of Neurons and Brain Diseases in Toyama
  • Place of Presentation: Toyama
  • Year and Date: 20110803-05
• [Presentation] Functional analysis of plated-derived growth factorβreceptor in neural stem cells (2011)
  • Author(s): Xu G, Ishii Y, Shen J, Sasahara M.
  • Organizer: The 6th International conference of Neurons and Brain Diseases in Toyama
  • Place of Presentation: Toyama
  • Year and Date: 20110803-05
• [Presentation] PDGFR-βis essential recruitment but not for survival of pericyte in adult mouse brain (2011)
  • Author(s): Shen J, Ishii Y, Xu G, Dang TC, Hamashima T, Matsushima T, Yamamoto S, Hattori Y, Takatsuru Y, Nabekura J, Sasahara M.
  • Organizer: The 6th International conference of Neurons and Brain Diseases in Toyama
  • Place of Presentation: Toyama
  • Year and Date: 20110803-05
• [Presentation] PDGFR-βsignal promotes repair process after cerebral ischemia (2011)
  • Author(s): 申杰,石井陽子,徐桂華,濱島丈,松島貴子,山本誠士,高鶴祐介,鍋倉淳一,笹原正清
  • Organizer: 第100回日本病理学会総会
  • Place of Presentation: 横浜
  • Year and Date: 20110428-30
• [Presentation] 血小板由来増殖因子β受容体の神経幹細胞の増殖と分化に対する役割の検討 (2011)
  • Author(s): 徐桂華,石井陽子,申杰,濱島丈,石澤伸,笹原正清
  • Organizer: 第100回日本病理学会総会
  • Place of Presentation: 横浜
  • Year and Date: 20110428-30
• [Presentation] The Involvement of PDGFR-βin the Maturation of Blood Vessel after Focal Cerebral Ischemia (2010)
  • Author(s): Shen J, Ishii Y, Xu G, Hamashima T, Matsushima T, Yamamoto S, Takatsuru Y, Nabekura J, Sasahara M.
  • Organizer: The 33rd Annual Meeting of the Japan Neuroscience Society(Neuro 2010)
  • Place of Presentation: Kobe
  • Year and Date: 20100902-04
• [Presentation] PDGFR-βdeletion improves diabetic nephropathy in CaM Kinase IIα(Thr286Asp) Transgenic Mice (2010)
  • Author(s): Suzuki H, Usui I, Kato I, Kanatani Y, Yamazaki Y, Fujisaka S, Senda S, Urakaze M, Sasahara M, Takasawa S, Okamoto H, Kobayashi M, Tobe K.
  • Organizer: American Diabetes Association(ADA) 70th Scientific Sessions
  • Place of Presentation: Orlando, USA
  • Year and Date: 20100625-29
• [Presentation] Neurovascular signaling of PDGF receptor beta protects CNS from insults, a study using conditional knockout mouse (2010)
  • Author(s): Sasahara M, Ishii Y, Shen J, Hamashima T.
  • Organizer: BIT's 1st Annual World Congress of NeuroTalk-2010
  • Place of Presentation: Singapore.(Invited lecture)
  • Year and Date: 20100625-28
• [Presentation] The Role for PDGFR-s as a Positive Regulator of Vessels Maturation after Focal Cerebral Ischemia in Mice (2010)
  • Author(s): Shen J, Ishii Y, Hamashima T, Sasahara M.
  • Organizer: BIT's 1st Annual World Congress of NeuroTalk-2010
  • Place of Presentation: Singapore
  • Year and Date: 20100625-28
• [Remarks]
  • URL: http://www.med.u-toyama.ac.jp/pathol2/index.html