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

PDGF抑制神经细胞死亡和促进突触发生的功能分析

• 批准号: 23590444
• 负责人: ISHII Yoko
• 金额: $ 3.24万
• 依托单位: University of Toyama
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2013
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23590444/
• 关键词: 細胞; 血小板由来増殖因子; 神経細胞; 血小板由来増殖因子 (PDGF); シナプス; 細胞死; synaptogenesis

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.

血小板衍生生长因子受体β（PDGFR-β）在突触发生中的作用，使用原代培养的小鼠海马神经元。与PDGFR-β保存的对照神经元相比，PDGFR-β条件性敲除海马神经元显示出较低的树突丝状伪足运动性和较低的棘数目。PDGFR-β基因敲除神经元中RhoA、VASP、PAL 1、ARPC 3的mRNA表达明显低于对照组。提示PDGFR-β通过这些细胞骨架相关基因在突触发生中发挥重要作用。我们还证明了PDGF-B对氧化应激的神经保护作用，使用培养的小鼠皮层神经元。PDGF-B可显著抑制氧化应激诱导的细胞内钙离子超载和钙蛋白酶失活。目前的研究支持PDGF-B/PDGFR-β可能是神经系统疾病和突触发生的潜在治疗靶点的观点。

项目成果

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

PDGF-β受体缺乏可改善胰岛素缺乏糖尿病模型小鼠的糖尿病肾病

• 发表时间: 2011
• 期刊: 日本病理学会会誌
• 作者: 石井陽子;鈴木ひかり;薄井 勲;加藤一郎;高沢 伸;岡本 宏;小林 正;戸邊一之;笹原正清
• 通讯作者: 笹原正清

Stage I ovarian cancer cases during early, mid and late pregnancy periods: Three case reports and review of the literature.

妊娠早、中、晚期I期卵巢癌病例：三例病例报告及文献复习。

• 发表时间: 2011
• 期刊: J. Obstet. Gynaecol. Res.
• 作者: Hasegawa T.;Ishii Y.;Yonezawa1 R.;Yoneda N.;Shima T.;Nakashima A.;Hidaka T. and Saito S.
• 通讯作者: Hidaka T. and Saito S.

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)

血小板源性生长因子-β受体对缺血脑血脑屏障功能很重要（PDGFR-β参与脑缺血后的血脑屏障功能）

• 发表时间: 2013
• 作者: 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
• 通讯作者: 倉茂洋一

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)

PDGFR-β在脑缺血后血脑屏障功能中的作用

• 发表时间: 2013
• 作者: 佐藤光;申杰;濱島丈;石井陽子;山本誠士;Dang Thanh Chung;笹原正清
• 通讯作者: 笹原正清

Cognitive and socio-emotional deficits in platelet-derived growth factor receptor-β gene knockout mice.

• DOI: 10.1371/journal.pone.0018004
• 发表时间: 2011-03-18
• 期刊: PloS one
• 影响因子: 3.7
• 作者: 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
• 通讯作者: Nishijo H