中国神经再生研究(英文版) ›› 2023, Vol. 18 ›› Issue (8): 1777-1781.doi: 10.4103/1673-5374.363179

• 原著:脑损伤修复保护与再生 • 上一篇    下一篇

脑卒中后亚急性期抑制Notch信号可促进纹状体星形胶质细胞转化为神经元

  

  • 出版日期:2023-08-15 发布日期:2023-02-23
  • 基金资助:
    国家自然科学基金项目(81801660和81771788)

Inhibition of Notch 1 signaling in the subacute stage after stroke promotes striatal astrocyte-derived neurogenesis

Xiao-Zhu Hao1, Cheng-Feng Sun1, Lu-Yi Lin1, Chan-Chan Li1, Xian-Jing Zhao1, Min Jiang2, Yan-Mei Yang1, *, Zhen-Wei Yao1, *   

  1. 1Department of Radiology, Huashan Hospital, Fudan University, Shanghai, China; 2Institutes of Science and State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai, China
  • Online:2023-08-15 Published:2023-02-23
  • Contact: Yan-Mei Yang, PhD, yym9876@sohu.com; Zhen-Wei Yao, PhD, aocnhnr@126.com.
  • Supported by:
    This study was supported by the National Natural Science Foundation of China, Nos. 81801660 (to XZH) and 81771788 (to YMY).

摘要:

抑制Notch1信号可促进脑卒中后星形胶质细胞源性的神经发生。为了检测Notch1信号在这一过程中的调节作用,实验构建了反应性星形胶质细胞移植治疗的大脑中动脉闭塞大鼠模型,于损伤后1,4,7d时以γ-分泌酶抑制剂(3,5-二氟苯乙酰基)-L-丙氨酰基-L-2-苯基甘氨酸叔丁酯阻断Notch1信号。结果显示,只有在损伤后第4天注射(3,5-二氟苯乙酰基)-L-丙氨酰基-L-2-苯基甘氨酸叔丁酯能够促进星形胶质细胞转化为神经元,且在磁共振弥散成像上表现为白质纤维传导束完整性出现一定程度修复,与神经功能恢复表现出一致性。表明Notch1信号抑制剂在脑卒中亚急性期可通过增强星形胶质细胞源性神经发生来促进神经修复。

https://orcid.org/0000-0002-5681-4308 (Zhen-Wei Yao); https://orcid.org/0000-0002-5142-9558 (Xiao-Zhu Hao)

关键词: Notch1, 神经发生, 星形胶质细胞, 神经元, 大脑中动脉闭塞, 亚急性期, (3,5-二氟苯乙酰基)-L-丙氨酰基-L-2-苯基甘氨酸叔丁酯, 磁共振成像, 弥散峰度成像, 神经修复

Abstract: Inhibition of Notch1 signaling has been shown to promote astrocyte-derived neurogenesis after stroke. To investigate the regulatory role of Notch1 signaling in this process, in this study, we used a rat model of stroke based on middle cerebral artery occlusion and assessed the behavior of reactive astrocytes post-stroke. We used the γ-secretase inhibitor N-[N-(3,5-diuorophenacetyl)-1-alanyl]-S-phenylglycine t-butylester (DAPT) to block Notch1 signaling at 1, 4, and 7 days after injury. Our results showed that only administration of DAPT at 4 days after stroke promoted astrocyte-derived neurogenesis, as manifested by recovery of white matter fiber bundle integrity on magnetic resonance imaging, which is consistent with recovery of neurologic function. These findings suggest that inhibition of Notch1 signaling at the subacute stage post-stroke mediates neural repair by promoting astrocyte-derived neurogenesis. 

Key words: astrocyte, diffusion kurtosis imaging, magnetic resonance imaging, middle cerebral artery occlusion, N-[N-(3,5-diuorophenacetyl)-1-alanyl]-S-phenylglycine t-butylester, neural repair, neurogenesis, neuron, Notch1 signaling, subacute stage