The effects of SOCS3 on neural stem cell fate and feasibility of the SOCS3-overexpressingneural stem cells for stake therapy

SOCS3对神经干细胞命运的影响以及SOCS3过表达神经干细胞用于桩治疗的可行性

• 批准号: 18591594
• 负责人: HATA Ryuji
• 金额: $ 2.57万
• 依托单位: Ehime University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2006
• 资助国家: 日本
• 起止时间: 2006 至 2007
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18591594/
• 关键词: SOCS3; Cerebral ischemia; Neurogenesis; Neural stem cell; Neurogenesis; cerebral ischemia; neurogenesis; neural stem cell

To investigate the effects of suppressors of cytokine signaling 3 (SOCS3) on neural stem cell fate, stem cells were infected with an adenoviral vector expressing SOCS3. Three days later, western blot analysis and immunocytochemical analysis revealed that the protein level of MAP2 and the number of MAP2-positive cells were significantly increased in SOCS3-transfected cells, while the protein level of GFAP and the number of GFAP-positive cells were significantly decreased. Furthermore, promoter assay revealed a significant reduction in the transcriptional level of signal transducer and activator of transcription 3 (Stat3) in the transfected cells. In addition, the mRNA levels of Notch family member (notchl) and inhibitory bHLH factors (hes5 and id3) were significantly up-regulated at one day after overexpression of SOCS3. At three days after transfection, the mRNA level of hes5 was significantly decreased, while that of notchl was still up-regulated. Moreover, all of SOCS3-positive cells expressed Nestin protein but did not express both MAP2 and GFAP proteins. These data indicate that overexpression of SOCS3 induced neurogenesis and inhibited astrogliogenesis in neural stem cells. Our data also show that SOCS3 promoted maintenance of neural stem cells. Furthermore, we evaluated the feasibility of the SOCS3-overexpressing neural stem cells for stroke therapy. Rats were subjected to focal cerebral ischemia for 60 min. Following reperfusion, neural stem cells over-expressing SOCS3 (1.0 x 10^5/5ul) were injected into common carotid artery. One day later, we evaluated the infarct size by TTC staining. However, there was no difference in infarct volume between the SOCS3-treated group and vehicle-treated group. We are now trying to evaluate other methods to transplant NSC into the brain, although we failed to demonstrate the feasibility SOCS3-overexpressing neural stem cells for stroke therapy this time.

为了研究细胞因子信号传导抑制因子 3 (SOCS3) 对神经干细胞命运的影响，用表达 SOCS3 的腺病毒载体感染干细胞。三天后，Western blot分析和免疫细胞化学分析显示，SOCS3转染细胞中MAP2蛋白水平和MAP2阳性细胞数量显着增加，而GFAP蛋白水平和GFAP阳性细胞数量显着降低。此外，启动子检测显示转染细胞中信号转导子和转录激活子 3 (Stat3) 的转录水平显着降低。此外，Notch家族成员(notch1)和抑制性bHLH因子(hes5和id3)的mRNA水平在SOCS3过表达后一天显着上调。转染后三天，hes5 mRNA水平显着下降，而notch1 mRNA水平仍上调。此外，所有SOCS3阳性细胞均表达Nestin蛋白，但不表达MAP2和GFAP蛋白。这些数据表明 SOCS3 的过度表达诱导神经发生并抑制神经干细胞中的星形胶质细胞发生。我们的数据还表明 SOCS3 促进神经干细胞的维持。此外，我们评估了 SOCS3 过表达神经干细胞用于中风治疗的可行性。使大鼠局灶性脑缺血60分钟。再灌注后，将过度表达 SOCS3 的神经干细胞 (1.0 x 10^5/5ul) 注射到颈总动脉中。一天后，我们通过 TTC 染色评估梗塞面积。然而，SOCS3治疗组和媒介物治疗组之间的梗塞体积没有差异。我们现在正在尝试评估将 NSC 移植到大脑中的其他方法，尽管这次我们未能证明 SOCS3 过表达神经干细胞用于中风治疗的可行性。

项目成果

Hematopoietic stem cells prevent hair cell death after transient cochlear ischemia through paracrine effects

• DOI: 10.1016/j.neuroscience.2006.12.067
• 发表时间: 2007-03
• 期刊: Neuroscience
• 影响因子: 3.3
• 作者: Tadashi Yoshida;N. Hakuba;Isao Morizane;Kensuke Fujita;Fang Cao;Pengxiang Zhu;N. Uchida;Kenji Kameda;M. Sakanaka;K. Gyo;Ryuji Hata

Upregulation of syntaxinl in the ischemic cortex following permanent focal ischemia in rats.

大鼠永久性局灶性缺血后缺血皮质中突触蛋白的上调。

• 发表时间: 2007
• 作者: Cao F;Hata R;Zhu P;Sakanaka M.
• 通讯作者: Sakanaka M.

Ginsenoside Rbl protects against damage to the spiral ganglion cells after cochlear ischemia

人参皂苷 Rbl 可防止耳蜗缺血后螺旋神经节细胞受损

• 发表时间: 2007
• 期刊: Neurosci Lett. 415
• 作者: Fujita K;Hakuba N;Hata R;Morizane I;Yoshida T;Shudou M;Sakanaka M;and Gyo K
• 通讯作者: and Gyo K

Protective effects of dihydrogeninsenoside Rb1 on ischemic brain damage and compressive spinal cord injury through upregulation of VEGF and Bcl-XL

二氢皂苷Rb1通过上调VEGF和Bcl-XL对缺血性脑损伤和压迫性脊髓损伤的保护作用

• 发表时间: 2007
• 作者: Hata R;Cao F;Zhu P;Samukawa K;Sakanaka M.
• 通讯作者: Sakanaka M.

Risk of conversion from mild memory impairment to Altzhemier'disease in a Japanese community(from the Nakayama Study)

日本社区中轻度记忆障碍转变为阿尔茨海默病的风险（来自中山研究）

• 发表时间: 2007
• 作者: Matsumoto N;Hata R;IshikawaT;Fukuhara R;Hokoishi K;Ikeda M;Tanabe H.
• 通讯作者: Tanabe H.