Functional analysis of PDGF in suppression of neuronal cell death and promotion of synaptogenesis

2013 Fiscal Year Final Research Report

• Project/Area Number: 23590444
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Experimental pathology
• Research Institution: University of Toyama
• Principal Investigator: ISHII Yoko 富山大学, 大学院医学薬学研究部(医学), 准教授 (00361949)
• Co-Investigator(Kenkyū-buntansha): SASAHARA Masakiyo 富山大学, 大学院医学薬学研究部, 教授 (20154015)
• Project Period (FY): 2011 – 2013
• Keywords: 細胞 / 血小板由来増殖因子 / 神経細胞

Research Abstract

The roles of platelet-derived growth factor receptor beta (PDGFR-beta) in synaptogenesis were examined using primary cultured mouse hippocampal neurons. PDGFR-beta conditional knockout hippocampal neurons showed lower motility of dendritic filopodia and lower numbers of spine as compared with PDGFR-beta preserved control neurons. mRNA expressions of RhoA, VASP, PAL1, ARPC3 in PDGFR-beta knockout neurons were significantly lower than those of control cells. It is suggested that PDGFR-beta has important role in synaptogenesis through these cytoskeleton related genes. We also demonstrated the neuroprotective effects of PDGF-B against oxidative stress using cultured mouse cortical neurons. PDGF-B significantly suppressed intracellular Calcium-ion overload and inactivation of calpain induced by oxidative stress. Present study supports the notion that PDGF-B/PDGFR-beta may be a potential therapeutic target of neurological diseases and synaptogenesis.

Research Products

• [Journal Article] PDGF suppresses oxidative stress induced Ca^<2+> overload and calpain activation in neurons (2014)
  • Author(s): Zheng LS, Ishii Y, Zhao QL, Kondo T, Sasahara M
  • Journal Title: Oxid Med Cell Longev Volume: (in press)
  • Peer Reviewed
• [Journal Article] Changes in Otx2 and Parvalbumin Immunoreactivity in the Superior Colliculus in the Platelet-Derived Growth Factor Receptor-βKnockout Mice (2014)
  • Author(s): Zhao J, Urakawa S, Matsumoto J, Li R, Ishii Y, Sasahara M, Peng Y, Ono T, Nishijo H
  • Journal Title: Biomed Res Int. Volume: (in press)
  • Peer Reviewed
• [Journal Article] The roles of PDGF in development and during neurogenesis in the normal and diseased nervous system (2013)
  • Author(s): Funa K, Sasahara M
  • Journal Title: J Neur oimmune Phar macol Volume: 9(2) Pages: 168-81
  • Peer Reviewed
• [Journal Article] Cilostazol ameliorates systemic insulin resistance in diabetic db/db mice by suppressing chronic inflammation in adipose tissue via modulation of both adipocyte and macrophage functions (2013)
  • Author(s): Wada T, Onogi Y, Kimura Y, Nakano T, Fusanobori H, Ishii Y, Sasahara M, Tsuneki H, Sasaoka T
  • Journal Title: Eur J Phar macol Volume: 707(1-3) Pages: 120-129
  • Peer Reviewed
• [Journal Article] SH2-containing inositol 5'-phosphatase 2 (SHIP2) selectively impaired hypothalamic insulin signalling and regulation of food intake in mice (2013)
  • Author(s): Ichihara Y, Wada T, Soeda Y, Ishii Y, Sasahara M, Tsuneki H, Sasaoka T
  • Journal Title: J Neur oendocr inol Volume: 25(4) Pages: 372-82
  • Peer Reviewed
• [Journal Article] Functional Analysis of Platelet-Derived Growth Factor Receptor-βin Neural Stem/Progenitor Cells (2013)
  • Author(s): Xu G, Shen J, Ishii Y, Fukuchi M, Dang TC, Zheng Y, Hamashima T, Fujimori T, Tsuda M, Funa K, Sasahara M
  • Journal Title: Neur oscience Volume: 238 Pages: 195-208
  • 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 Endocr inol Metab Volume: 303(4) Pages: E445-56
  • Peer Reviewed
• [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 Cer eb Blood Flow Metab Volume: 32(2) Pages: 353-67
  • 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(6) Pages: 1371-8
  • 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(11) Pages: 2953-62
  • 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 YI, Inoue H, Sasahara M
  • Journal Title: Nephr ol Dial Tr ansplant Volume: 26(2) Pages: 458-68
  • 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
  • Journal Title: Hippocampus Volume: 21(6) Pages: 678-87
  • Peer Reviewed
• [Presentation] 幹細胞、癌幹細胞と細胞診について血小板由来増殖因子(PDGF)は神経幹細胞の制御に関与する (2013)
  • Author(s): 笹原正清
  • Organizer: 第52回日本臨床細胞学会秋期大会
  • Place of Presentation: 大阪
  • Year and Date: 20131102-03
• [Presentation] 血小板由来増殖因子β受容体は虚血脳における脳血液関門の機能に重要である(PDGFR-βis involved in BBB function after cerebral ischemia) (2013)
  • Author(s): 笹原正清, 申杰, 石井陽子, 山本誠士, 濱島丈, Dang Thanh Chung, 松島貴子, 倉茂洋一
  • Organizer: Neuro2013
  • Place of Presentation: 京都
  • Year and Date: 20130620-23
• [Presentation] PDGF受容体は脳血液関門のバリアー機能に重要である (2013)
  • Author(s): 笹原正清, Shen Jie, 石井陽子, 濱島丈, 山本誠士, 松島貴子, 倉茂洋一, Dang Thanh Chung
  • Organizer: 第102回日本病理学会総会
  • Place of Presentation: 札幌
  • Year and Date: 20130606-08
• [Presentation] 神経特異的なPDGFR-αノックアウトマウスにおける髄鞘形成障害 (2013)
  • Author(s): 濱島丈, 石井陽子, Shen Jie, 山本誠士, 松島貴子, 倉茂洋一, 笹原正清
  • Organizer: 第102回日本病理学会総会
  • Place of Presentation: 札幌
  • Year and Date: 20130606-08
• [Presentation] 血管内皮細胞の炎症病態に関連するmiRNAの解析 (2013)
  • Author(s): 山本誠士, 東英梨月, 村松昌, 濱島丈, 石井陽子, 新飯田俊平, 笹原正清
  • Organizer: 第102回日本病理学会総会
  • Place of Presentation: 札幌
  • Year and Date: 20130606-08
• [Presentation] 血小板由来増殖因子α受容体は線維芽細胞に発現し新生肉芽形成に関与する (2013)
  • Author(s): 堀川慎二郎, 石井陽子, 山本誠士, 濱島丈, 笹原正清
  • Organizer: 第102回日本病理学会総会
  • Place of Presentation: 札幌
  • Year and Date: 20130606-08
• [Presentation] 脳虚血後のBBB機能におけるPDGFR-βの役割(Roles of PDGFR-βin BBB functions after cerebral ischemia) (2013)
  • Author(s): 佐藤光, 申杰, 濱島丈, 石井陽子, 山本誠士, Dang Thanh Chung, 笹原正清
  • Organizer: 第102回日本病理学会総会
  • Place of Presentation: 札幌
  • Year and Date: 20130606-08
• [Presentation] PDGF受容体ノックアウトマウスにおける認知能力,社会性および情動の異常 (2013)
  • Author(s): Dang Thanh Chung, 濱島丈, 石井陽子, 中村友也, 堀悦郎, 西条寿夫, 笹原正清
  • Organizer: 第102回日本病理学会総会
  • Place of Presentation: 札幌
  • Year and Date: 20130606-08
• [Presentation] マウス皮膚線維芽細胞の遊走におけるPDGF受容体の役割の解明 (2013)
  • Author(s): 山田浩太, 笹原正清, 石井陽子, 濱島丈, 山本誠士
  • Organizer: 第102回日本病理学会総会
  • Place of Presentation: 札幌
  • Year and Date: 20130606-08
• [Presentation] PDGF-β受容体欠損神経幹細胞の多分化能の検討 (2013)
  • Author(s): 浜田さおり, 徐桂華, 申杰, 石井陽子, 笹原正清
  • Organizer: 第102回日本病理学会総会
  • Place of Presentation: 札幌
  • Year and Date: 20130606-08
• [Presentation] PDGF-β受容体欠損アストロサイトの機能の解析 (2013)
  • Author(s): 布村晴香, 石井陽子, 浜田さおり, 濱島丈, 笹原正清
  • Organizer: 第102回日本病理学会総会
  • Place of Presentation: 札幌
  • Year and Date: 20130606-08
• [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.(Functional Analysis of Platelet-Derived Growth Factor Receptor-βin Neural Stem/Progenitor Cells.) (2012)
  • Author(s): 徐桂華, 石井陽子, 申杰,福地守, Dang Thanh Chung, 鄭陽, 濱島丈, 津田正明, 笹原正清
  • Organizer: The 35th Annual Meeting of the Japan Neuroscience Society (Neuroscence2012)
  • Place of Presentation: Nagoya
  • Year and Date: 20120918-21
• [Presentation] 新規栄養因子様化合物T-817MAは統合失調症および自閉症様症状を呈するPDGFR-βKOマウスにおける行動障害およびガンマオシレーション障害を改善する. (T-817MA, a novel neurotophic agent, ameliorates deficits in behaviors and gamma oscillation in PDGFR-βKO mice witth schizophrenia- and autism-like symptoms.) (2012)
  • Author(s): 中村友也, 堀悦郎, 高村雄策, 寺澤彩乃, 濱島丈, 石井陽子, 松島貴子, 小野武年, 笹原正清, 西條寿夫
  • Organizer: The 35th Annual Meeting of the Japan Neuroscience Society (Neuroscence 2012)
  • Place of Presentation: Nagoya
  • Year and Date: 20120918-21
• [Presentation] Platelet-derived growth factor receptor beta signal could contribute to vulnerability and repairability of glomerular capillary structure (2012)
  • Author(s): Nakagawa T, Ichikawa K, Miyamoto M, Takabayashi D, Yamazaki H, Kakeshita K, Koike T, Kagitani S, Tomoda F, Hamashima T, Ishii Y, Inoue H. and Sasahara M
  • Organizer: EUROPEAN RENAL ASSOCIATION - EUROPEAN DIALYSIS AND TRANSPLANT ASSOCIATION 49th ERA-EDTA Congress
  • Place of Presentation: Paris, FRANCE
  • Year and Date: 20120524-27
• [Presentation] 肉芽形成モデルにおける血小板由来増殖因子α受容体の機能解析 (2012)
  • Author(s): 堀川慎二郎, 申杰, 徐桂華, 濱島丈, 松島貴子, 藤川美和, 倉茂洋一, 石井陽子, 笹原正清
  • Organizer: 第101回日本病理学会総会
  • Place of Presentation: 東京
  • Year and Date: 20120426-28
• [Presentation] 血小板由来成長因子β受容体遺伝子ノックアウトマウスにおけるガンマオシレーションの障害 (2012)
  • Author(s): 中村友也, Nguyen PTH, 堀悦郎, 浦川将, 上野照子, Zhao J, Li R, Bac ND, 濱島丈, 石井陽子, 松島貴子, 小野武年, 笹原正清, 西条寿夫
  • Organizer: 第89回日本生理学会大会
  • Place of Presentation: 松本
  • Year and Date: 20120329-31
• [Presentation] Neuroprotective Effects of PDGF Against Oxidative Stress and the Signaling Pathway Involved (2011)
  • Author(s): Ishii Y, Zheng L and Sasahara M
  • Organizer: The 6^<th> 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 and Sasahara M
  • Organizer: The 6^<th> 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 6^<th> International conference of Neurons and Brain Diseases in Toyama
  • Place of Presentation: Toyama
  • Year and Date: 20110803-05
• [Presentation] PDGF-β受容体の欠損は,インスリン分泌低下型糖尿病モデルマウスの糖尿病腎症を改善する (2011)
  • Author(s): 石井陽子, 鈴木ひかり, 薄井勳, 加藤一郎, 高沢伸, 岡本宏, 小林正, 戸邊一之, 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] 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] Antagonism of mineralocorticoid receptor ameliorates systemic insulin resistance and steatohepatitis in a novel mouse model of non-alcoholic steatohepatitis (NASH) utilizing liver-specific SREBP1c transgenic mice (2011)
  • Author(s): Wada T, Miyashita Y, Sasaki M, Ishii Y, Sasahara M, Tsuneki H, Sasaoka T
  • Organizer: Keystone Symposia : Type2 Diabetes, Insulin Resistance and Metabolic Dysfuncetion
  • Place of Presentation: Keystone, CO, U.S.A.
  • Year and Date: 20110112-17
• [Presentation] Eplerenone improves insulin sensitivity by suppressing inflammation in both liver and adipose tissue of NASH model mice (2011)
  • Author(s): Sasaki M, Wada T, Miyashita Y, Ishii Y, Sasahara M, Tsuneki H and Sasaoka T
  • Organizer: The 4^<th> International Aldosterone Forum in Japan
  • Place of Presentation: Tokyo
  • Year and Date: 2011-05-14
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