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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Authors: | Hui Lei Yu Zhang Longjian Huang Shaofeng Xu Jiang Li Lichao Yang Ling Wang Changhong Xing Xiaoliang Wang Ying Peng |
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Institution: | 1.State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica,Chinese Academy of Medical Sciences & Peking Union Medical College,Beijing,China;2.Departments of Radiology and Neurology, Massachusetts General Hospital,Harvard Medical School,Charlestown,USA;3.Pharmacology Department, Institute of Materia Medica,Chinese Academy of Medical Sciences & Peking Union Medical College,Beijing,China |
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Abstract: | Alzheimer’s disease (AD) is characterized by extracellular accumulation of β-amyloid peptides (Aβ) 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. |
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