L-3-n-Butylphthalide Regulates Proliferation, Migration, and Differentiation of Neural Stem Cell In Vitro and Promotes Neurogenesis in APP/PS1 Mouse Model by Regulating BDNF/TrkB/CREB/Akt Pathway
L-3-n-Butylphthalide Regulates Proliferation, Migration, and Differentiation of Neural Stem Cell In Vitro and Promotes Neurogenesis in APP/PS1 Mouse Model by Regulating BDNF/TrkB/CREB/Akt Pathway
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L-3-正丁基苯酞通过调节 BDNF/TrkB/CREB/Akt 通路调节体外神经干细胞的增殖、迁移和分化，促进 APP/PS1 小鼠模型的神经发生
DOI：
10.1007/s12640-018-9905-3
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发表时间：
2018-10-01
影响因子：
3.7
通讯作者：
Peng, Ying
中科院分区：
文献类型：
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作者：
Lei, Hui;Zhang, Yu;Peng, Ying
阿尔茨海默病 (AD) 的特点是细胞外 β-淀粉样肽 (Aβ) 的积累和细胞内神经原纤维缠结，以及认知能力下降和神经变性。认知缺陷被认为是由于海马神经发生功能障碍所致。尽管 L-3-正丁基苯酞 (L-NBP) 已在多种 AD 动物模型中显示出有益作用，但其潜在的分子机制仍不清楚。在这项研究中，我们研究了 L-NBP 对体外和体内神经发生的影响。 L-NBP在体外促进神经干细胞的增殖和迁移并诱导神经元分化。在 APP/PS1 小鼠中，L-NBP 诱导齿状回神经发生并改善认知功能。此外，L-NBP 显着增加 APP/PS1 小鼠海马 BDNF 和 NGF 的表达、其同源受体的酪氨酸磷酸化以及 Akt 和 CREB Ser133 的磷酸化。这些结果表明，L-NBP 可能刺激海马神经干细胞的增殖、迁移和分化，并逆转 APP/PS1 小鼠的认知缺陷。 BDNF/TrkB/CREB/Akt信号通路可能参与其中。
Alzheimer's disease (AD) is characterized by extracellular accumulation of beta-amyloid peptides (A beta) and intracellular neurofibrillary tangles, along with cognitive decline and neurodegeneration. The cognitive deficit is considered to be due to the dysfunction of hippocampal neurogenesis. Although L-3-n-butylphthalide (L-NBP) has been shown beneficial effects in multiple AD animal models, the underlying molecular mechanisms are still elusive. In this study, we investigated the effects of L-NBP on neurogenesis both in vitro and in vivo. L-NBP promoted proliferation and migration of neural stem cells and induced neuronal differentiation in vitro. In APP/PS1 mice, L-NBP induced neurogenesis in the dentate gyrus and improved cognitive functions. In addition, L-NBP significantly increased the expressions of BDNF and NGF, tyrosine phosphorylation of its cognate receptor, and phosphorylation of Akt as well as CREB at Ser133 in the hippocampus of APP/PS1 mice. These results indicated that L-NBP might stimulate the proliferation, migration, and differentiation of hippocampal neural stem cells and reversed cognitive deficits in APP/PS1 mice. BDNF/TrkB/CREB/Akt signaling pathway might be involved.