中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2019, Vol. 14 ›› Issue (4): 613-620.doi: 10.4103/1673-5374.248519

• 原著:脑损伤修复保护与再生 • 上一篇    下一篇

木犀草素诱导Ts65Dn小鼠海马神经的发生

  

  • 出版日期:2019-04-15 发布日期:2019-04-15
  • 基金资助:

    常州市高等卫生人才培养计划项目（2016CZLJ013），常州市科技支撑项目（社会发展）（CE20175021），常州市应用基础研究项目（CJ20160036）

Luteolin induces hippocampal neurogenesis in the Ts65Dn mouse model of Down syndrome

Wen-Bo Zhou 1 , Zong-Ning Miao 2, , Bin Zhang 1 , Wei Long 1 , Fang-Xiu Zheng 1 , Jing Kong 1 , Bin Yu 1   

  1. 1 Changzhou Women and Children Health Hospital Affiliated to Nanjing Medical University, Changzhou, Jiangsu Province, China
    2 The Stem Cell Research Laboratory, Wuxi Third People’s Hospital, Wuxi, Jiangsu Province, China
  • Online:2019-04-15 Published:2019-04-15
  • Contact: Bin Yu, PhD, ybcz0519@163.com.
  • Supported by:

    This study was supported by the Project Funding for the Training of High Level Health Professionals in Changzhou of China, No. 2016CZLJ013 (to BY); the Science and Technology Support Project of Changzhou of China, No. Social Development CE20175021 (to BY); the Application Basic Research Project of Changzhou of China, No. CJ20160036 (to WBZ).

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摘要：

研究证实天然黄酮类化合物木犀草素具有神经营养活性，为此，作者在本次实验中拟探索其用于治疗唐氏综合征的可能。实验设计以Ts65Dn小鼠作为唐氏综合征模型，给予12周龄小鼠连续4周腹腔注射10 mg/kg木犀草素治疗。（1）以Morris水迷宫检测小鼠学习记忆能力，以新物体识别实验检测小鼠识别新物体的能力，以免疫组化染色检测海马齿状回中神经干细胞标志物巢蛋白、星形胶质细胞标志物胶质纤维酸性蛋白、未成熟神经元标志物DCX、成熟神经元标志物NeuN及细胞增殖标志物Ki67的免疫阳性反应，以尼氏染色观察海马齿状回中神经细胞形态和数量的变化，以Western blot分析海马中脑源性神经营养因子和p-ERK1/2表达水平；（2）结果发现木犀草素能明显改善Ts65Dn小鼠的学习记忆能力以及识别新物体的能力，促进海马齿状回中神经细胞的增殖，巢蛋白和胶质纤维酸性蛋白免疫阳性反应增加，海马齿状回中颗粒下区DCX+阳性神经元和颗粒层中NeuN+阳性神经元数量增加，海马中脑源性神经营养因子及p-ERK1/2表达增加；（2）实验结果证实木犀草素可改善Ts65Dn小鼠行为表现以及海马的神经发生，且这个过程可能与脑源性神经营养因子/细胞外调节蛋白激酶信号通路激活有关。

orcid: 0000-0001-7796-7314(Bin Yu)

关键词: 木犀草素, 海马, Ts65Dn小鼠, 神经发生, 脑源性神经营养因子/细胞外调节蛋白激酶信号通路, 巢蛋白, GFAP, NeuN, 唐氏综合征, 神经再生

Abstract:

Studies have shown that the natural flavonoid luteolin has neurotrophic activity. In this study, we investigated the effect of luteolin in a mouse model of Down syndrome. Ts65Dn mice, which are frequently used as a model of Down syndrome, were intraperitoneally injected with 10 mg/kg luteolin for 4 consecutive weeks starting at 12 weeks of age. The Morris water maze test was used to evaluate learning and memory abilities, and the novel object recognition test was used to assess recognition memory. Immunohistochemistry was performed for the neural stem cell marker nestin, the astrocyte marker glial fibrillary acidic protein, the immature neuron marker DCX, the mature neuron marker NeuN, and the cell proliferation marker Ki67 in the hippocampal dentate gyrus. Nissl staining was used to observe changes in morphology and to quantify cells in the dentate gyrus. Western blot assay was used to analyze the protein levels of brain-derived neuro¬trophic factor (BDNF) and phospho-extracellular signal-regulated kinase 1/2 (p-ERK1/2) in the hippocampus. Luteolin improved learning and memory abilities as well as novel object recognition ability, and enhanced the proliferation of neurons in the hippocampal dentate gyrus. Furthermore, luteolin increased expression of nestin and glial fibrillary acidic protein, increased the number of DCX+ neurons in the gran¬ular layer and NeuN+ neurons in the subgranular region of the dentate gyrus, and increased the protein levels of BDNF and p-ERK1/2 in the hippocampus. Our findings show that luteolin improves behavioral performance and promotes hippocampal neurogenesis in Ts65Dn mice. Moreover, these effects might be associated with the activation of the BDNF/ERK1/2 pathway.

Key words: nerve regeneration, luteolin, hippocampus, Ts65Dn mice, neurogenesis, ERK, BDNF, nestin, GFAP, NeuN, Down syndrome, neural regeneration