[1]宁文洁,刘使君,孙源培,等.丙戊酸促进小鼠神经干细胞分化成神经元及其影响机制[J].华侨大学学报(自然科学版),2025,(1):79-86.[doi:10.11830/ISSN.1000-5013.202405017]
　NING Wenjie,LIU Shijun,SUN Yuanpei,et al.Valproic Acid Promotes Differentiation of Mouse Neural Stem Cells Into Neurons and Its Mechanism of Effect[J].Journal of Huaqiao University(Natural Science),2025,(1):79-86.[doi:10.11830/ISSN.1000-5013.202405017]
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丙戊酸促进小鼠神经干细胞分化成神经元及其影响机制()
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《华侨大学学报（自然科学版）》[ISSN:1000-5013/CN:35-1079/N]

卷:
期数:
2025年第1期
页码:
79-86
栏目:
出版日期:
2025-01-10

文章信息/Info

Title:
Valproic Acid Promotes Differentiation of Mouse Neural Stem Cells Into Neurons and Its Mechanism of Effect
文章编号:
1000-5013(2025)01-0079-08
作者:
宁文洁1;  刘使君1;  孙源培1;  赖靖尧2;  王立强1;  侯志勇1; 3
1. 华侨大学 生物医学学院, 福建 泉州 362021;2. 神岐生命科技(福建)有限公司, 福建 泉州 362005;3. 解放军962医院, 黑龙江 哈尔滨 150080
Author(s):
NING Wenjie1;  LIU Shijun1;  SUN Yuanpei1; LAI Jingyao2;  WANG Liqiang1;  HOU Zhiyong1; 3
1. School of Biomedical Sciences, Huaqiao University, Quanzhou 362021, China; 2. Shenqi Life Science and Technology(Fujian)Limited Company, Quanzhou 362005, China; 3. PLA 962 Hospital, Harbin 150080, China
关键词:
神经干细胞;  神经元;  细胞周期蛋白;  丙戊酸;  Wnt/β-catenin通路
Keywords:
neural stem cells;  neurons;  cell cycle protein;  valproic acid;  Wnt/β-catenin pathway
分类号:
R329.2
DOI:
10.11830/ISSN.1000-5013.202405017
文献标志码:
A
摘要:
为了探究丙戊酸(VPA)促进小鼠神经干细胞(NSCs)分化成神经元的可能机制,从小鼠脑中分离神经干细胞并进行传代培养,再将其在不同类型分化培养基中重新接种,诱导细胞分化为神经元,用免疫荧光染色检测神经元特异性标志物的表达情况,并采用qRT-PCR分析研究VPA处理前、后Wnt/β-catenin信号通路中关键分子表达水平。结果表明:分离后传代培养的NSCs悬液内Nestin和Pax6阳性细胞比例居高,分化后细胞呈现出显著神经元形态,且神经元标志物β-微管蛋白(TUJ1)、双皮质素(DCX)和微管相关蛋白2(MAP2)在分化后表达水平显著提高;与正常组相比,VPA处理组中Wnt-3α,β-catenin和cyclin D1的mRNA相对表达量上升,p21的mRNA相对表达量降低;Wnt/β-catenin信号通路的抑制剂FH535能显著减弱VPA中NSCs分化成神经元的过程。
Abstract:
To investigate the possible mechanisms by which valproic acid(VPA)promotes the differentiation of mouse neural stem cells(NSCs)into neurons, neural stem cell were isolated from mouse brain and passaged in culture, then re-inoculated in different types of differentiation medium to induce cell differentiation into neurons, and the expression of neuron-specific markers was detected by immunofluorescence staining, and the expression levels of key molecules in the Wnt/β-catenin signalling pathway were investigated before and after VPA treatment by qRT-PCR. The results showed that the proportion of Nestin and Pax6 positive cells within suspensions of NSCs cultured in passages after isolation was high, the differentiated cells showed significant neuronal morphology, and the expression levels of neuronal markers β-Tubulin(TUJ1), Doublecortin(DCX)and recombinant microtubule associated protein 2(MAP2)were significantly increased after differentiation. Compared with the normal group, the mRNA relative expression levels of Wnt-3α, β-catenin and cyclin D1 was increased, and the mRNA relative expression levels of p21 protein was decreased in the VPA-treated group. FH535, an inhibitor of the Wnt/β-catenin signalling pathway, significantly attenuated the differentiation of NSCs into neurons in VPA.

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备注/Memo

备注/Memo:
收稿日期: 2024-05-21
通信作者: 侯志勇(1972-),男,副主任药师,主要从事创新药物的研究。E-mail:mpp5358@163.com。
基金项目: 国家重点研发计划项目(2016YFE0101700); 福建省高校产学合作重大项目(2019Y4007); 华侨大学研究生科研创新基金资助项目(18013071019)https://hdxb.hqu.edu.cn/
更新日期/Last Update: 2025-01-20