Reconstruction of disturbed brain function with neural stem cells from the investigation of the mechanism and induction to neuronal differentiation by trophic factor

从机制研究及营养因子诱导神经元分化的神经干细胞重建受损脑功能

• 批准号: 16500203
• 负责人: HIDA Hideki
• 金额: $ 2.37万
• 依托单位: Nagoya City University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2004
• 资助国家: 日本
• 起止时间: 2004 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-16500203/
• 关键词: embryonic stem cell; dopaminergic neuron; neuronal differentiation; neural stem cell; cell cycle; low oxygen; hupoxia inducible factor-1; pleiotrophin; 胚性幹(ES)細胞; チロシン水酸化酵素; p27^<kip1>; HIF-1α; cdk5; cytokine; LIF; wnt5a; 低酸素条件; 細胞培養濃度

We investigate 1) how to increase of the number of dopaminergic (DAergic) neurons from embryonic stem (ES) cell-derived neural stem cells (NSCs) and 2) the mechanism of DAergic differentiation, and we also carried out basic research for neural transplantation using NSCs for the recovery of disturbed brain function. Data are summarized as follows.1) DAergic differentiation from NSCs are induced by low physiological oxygen in the fetal brain (3.5% 02) or cytokine mixture (IL-113, IL-11, LIF, GDNF) which is enhanced in DA-depleted striatum. 2) Cell cycle inhibition in G 1/S phase by the pre-treatment with deferoxamine (DFO) induced neuronal differentiation relating to prolonged p27^<kiP1> elevation and activation of the neuroD signaling pathway. 3) DAergic differentiation induced by pleiotrophin (PTN), IL-1β and 3.5% oxygen is mediated by the mechanism relating to enhanced expression of HIF-1 a. 4) Investigation for the question if PTN promotes the survival of grafted cells clearly reveals that PTN treatment to donor cells promotes cell survival in the striatum after transplantation in which most grafted cells are close to cell death, resulting in better functional recovery.

我们研究1）如何增加来自胚胎（ES）细胞衍生的神经元细胞（NSC）和2）Daergic分化机制的多巴胺能（DAERIC）神经元的数量，我们还使用NSC进行了NSC进行神经移植的基础研究，以恢复受影响的大脑功能的恢复。数据总结如下。1）与NSC的DAERAGIC分化是由胎儿脑（3.5％02）或细胞因子混合物（IL-113，IL-11，LIF，GDNF，GDNF）诱导的。 2）通过脱氧胺（DFO）诱导的神经元分化与延长的p27^<kip1>升高和神经障碍信号途径的激活有关的神经元分化，通过脱氧胺（DFO）诱导的神经元分化抑制细胞周期。 3）由pleiotiotrophin（PTN），IL-1β和3.5％氧诱导的Daergic分化是通过与增强HIF-1 A表达相关的机制介导的。 4）研究以下问题，PTN是否促进了移植细胞的存活情况，清楚地表明，对供体细胞的PTN治疗促进了移植后大多数移植细胞接近细胞死亡的纹状体中的细胞存活，从而导致更好的功能恢复。

项目成果

「研究成果報告書概要(欧文)」より

摘自《研究结果报告摘要（欧洲）》

• 发表时间: 2006
• 期刊: Seibutsu Butsuri 46(1)
• 作者: Yasushi Shigeri;Keiko Shimamoto
• 通讯作者: Keiko Shimamoto

神経移植におけるプレイオトロプィンの効果

多效素在神经移植中的作用

• 发表时间: 2005
• 期刊: 脳神経外科ジャーナル 14(8)
• 作者: Ando;Z.;飛田秀樹
• 通讯作者: 飛田秀樹

Involvement of nitric oxide for the 3- nitropropionic acid-induced striatal toxicity in rats.

一氧化氮参与 3-硝基丙酸诱导的大鼠纹状体毒性。

• 发表时间: 2006
• 期刊: Brain Res. 1108
• 作者: Deshpande;S.B.;Hida;H;Takei;N.;Masuda;T.;Baba;H.Nishino;H.
• 通讯作者: H.

Treatment with deferoxamine increases neurons from neural stem/progenitor cells

• DOI: 10.1016/j.brainres.2006.02.046
• 发表时间: 2006-05-30
• 期刊: BRAIN RESEARCH
• 影响因子: 2.9
• 作者: Kim, Hye-Jung;Hida, Hideki;Nishino, Hitoo
• 通讯作者: Nishino, Hitoo

Pleiotrophin promotes functional recovery after neural transplantation in rats

• DOI: 10.1097/wnr.0b013e328011398e
• 发表时间: 2007-01-22
• 期刊: NEUROREPORT
• 影响因子: 1.7
• 作者: Hida, Hideki;Masuda, Tadashi;Nishino, Hitoo
• 通讯作者: Nishino, Hitoo