The Regulatory Mechanism of Neurogenesis by IGF-1 in Adult Mice

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• 作者：Honghua Yuan (1)
  Renjin Chen (2)
  Lianlian Wu (1)
  Quangang Chen (2)
  Ankang Hu (2)
  Tengye Zhang (1)
  Zhenzhen Wang (1)
  Xiaorong Zhu (2)
  
  1. Research Center for Neurobiology ; Xuzhou Medical College ; Xuzhou ; Jiangsu ; China
  2. Laboratory Animal Center ; Xuzhou Medical College ; Xuzhou ; 221004 ; Jiangsu ; China
  
• 关键词：IGF ; 1 ; Transgenic mice ; Neural stem cells ; Regulatory mechanism ; Differentiation ; Proliferation
• 刊名：Molecular Neurobiology
• 出版年：2015
• 出版时间：April 2015
• 年：2015
• 卷：51
• 期：2
• 页码：512-522
• 全文大小：2,753 KB
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• 刊物主题：Neurosciences; Neurobiology; Cell Biology; Neurology;
• 出版者：Springer US
• ISSN：1559-1182

文摘

Growth factors like insulin-like growth factor 1 (IGF-1) is reported to mediate neurogenesis in the subgranular zone (SGZ) and the subventricular zone (SVZ) of the adult mammalian brain, but its regulatory mechanism remains unclear. We generated transgenic mice overexpressing IGF-1 specifically in neural stem cells (NSCs) and assessed the effect of IGF-1 on neurogenesis in adult mice NSCs. Overexpression of IGF-1 could stimulate the expression of phospho-Akt and phospho-ERK1/2 while inducing proliferation and differentiation of NSCs in the SGZ and SVZ. The MEK/ERK inhibitor U0126 could inhibit ERK1/2 phosphorylation, further inhibiting the proliferation of NSCs in the SGZ and SVZ but had no effect on the phosphorylation of Akt. By contrast, The PI3K/Akt inhibitor LY294002 inhibited phosphorylation of Akt and differentiation of NSCs in the SGZ and SVZ, resulting in no change in the proliferation of NSCs and ERK1/2 phosphorylation. These results demonstrate that IGF-1 upregulates the proliferation of NSCs by triggering MEK/ERK pathway signaling in the adult mice SGZ and SVZ. Meanwhile, IGF-1 also induces differentiation of NSCs via the PI3K/Akt pathway in adult mice. However, we found no evidence of crosstalk between the PI3K/Akt and MEK/ERK pathways in adult mice NSCs. Our work provides new experimental evidence of the involvement of the PI3K/Akt and MEK/ERK pathways in the proliferation and differentiation of the NSCs of adult mice.