<strong>Secoisolariciresinol Reduces Behavioral Despair and Regulates Hippocampal BDNF Expression in Ovariectomized Mice</strong>

神经药理学报››2013,Vol. 3››Issue (2): 13-25.

Secoisolariciresinol Reduces Behavioral Despair and Regulates Hippocampal BDNF Expression in Ovariectomized Mice

YAO Guang-Yin, JI Dan-Yang, ZHOU Wei-Dong, YAO Hai-Yan, KU Bao-Shan, YANG Dong-Hui

1．北京大学医学部药学系天然药物与仿生药物国家重点实验室，北京，100091，中国
2．北京师范大学生命科学院细胞生物学系，北京，100875，中国
3．北京鼎国昌盛生物科技有限责任公司，北京，102209，中国

出版日期:2013-04-26发布日期:2014-06-27
通讯作者:杨东辉，女，副教授，硕士研究生导师；研究方向：天然产物的生物转化及生物合成；Tel.: +86-10-82801559， E-mail: ydhui@bjmu.edu.cn
作者简介:姚广印，男，博士；研究方向：神经药理；E-mail:ygy913@163.com
基金资助:

国家科技重大专项重大新药创制项目（No.2011ZX09102-011-06）

Secoisolariciresinol Reduces Behavioral Despair and Regulates Hippocampal BDNF Expression in Ovariectomized Mice

YAO Guang-Yin, JI Dan-Yang, ZHOU Wei-Dong, YAO Hai-Yan, KU Bao-Shan, YANG Dong-Hui

1 State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, 100191, China,
2 College of Life Sciences, Beijing Normal University, Beijing, 100875, China
3 Beijing Dingguochangsheng Biotechnology Co. Ltd, Beijing, 102209, China

Online:2013-04-26Published:2014-06-27
Contact:杨东辉，女，副教授，硕士研究生导师；研究方向：天然产物的生物转化及生物合成；Tel.: +86-10-82801559， E-mail: ydhui@bjmu.edu.cn
About author:姚广印，男，博士；研究方向：神经药理；E-mail:ygy913@163.com
Supported by:

国家科技重大专项重大新药创制项目（No.2011ZX09102-011-06）

摘要/Abstract

摘要：目的：探讨开环异落叶松树脂酚（Secoisolariciresinol，SECO)对卵巢摘除(OVX)小鼠抗更年期抑郁的机制。方法：利用卵巢摘除小鼠建立更年期抑郁模型，通过悬尾测试和强迫游泳测试，检测SECO抗抑郁效果。通过检测脑源性神经生长因子（BDNF）在小鼠海马区mRNA和蛋白水平的表达，Akt和pAkt在海马区的蛋白水平的表达以及BrdU标记的新生细胞的数量，探讨SECO的抗抑郁机制。结果：SECO（10或20mg/kg）能显著减少OVX小鼠的悬尾不动时间和强迫游泳不动时间，具有抗抑郁效果。给予SECO后，小鼠海马区BDNF mRNA和蛋白水平与模型组相比显著升高，免疫荧光结果显示BDNF在海马CA1、CA3及DG区的表达增多（P<0.05）。同时，海马区的新生神经细胞数量增多以及pAkt表达升高。结论：SECO通过BDN介导的Akt/pAkt信号通路显示出抗抑郁效果，其作为潜在的治疗更年期抑郁药物具有良好的应用前景。

关键词:开环异落叶松树脂酚（SECO）,悬尾测试,强迫游泳测试,脑源性神经生长因子（BDNF）

Abstract:Objective: To investigate the antidepressant-like effect and the possible mechanism of Secoisolariciresinol (SECO) in ovariectomized (OVX) mice.Methods: OVX mice were used as a menopausal animal model and tail suspension and forced swimming tests were conducted to measure the effects of SECO on behavioral despair. The expression levels of brain-derived neurotrophic factor (BDNF) mRNA and protein were measured by real-time PCR, Western blot analysis and immunofluorescence. In addition, Akt and pAkt were tested by Western blot analysis and BrdU-labeled cells were observed by immunofluorescence.Results: SECO (10 and 20 mg/kg, p.o. ) significantly reduced the immobility duration of OVX mice in both forced swimming and tail suspension tests. Administration of SECO significantly increased BDNF levels in hippocampus. Moreover, this study demonstrated that SECO increased BDNF immunoreactivity in hippocampal CA1, CA3 and DG pyramidal neurons, and BrdU-labeled cell number in the DG subfield. SECO also significantly increased the phosphorylation of Akt.Conclusion: SECO has the potential to treat depression in menopausal women which may be attributed to BDNF-mediated PI3K/Akt signaling pathway.

Key words:Secoisolariciresinol (SECO),Ovariectomized mice,Forced swimming,Tail suspension,Brain-derived neurotrophic factor (BDNF)

YAO Guang-Yin, JI Dan-Yang, ZHOU Wei-Dong, YAO Hai-Yan, KU Bao-Shan, YANG Dong-H.Secoisolariciresinol Reduces Behavioral Despair and Regulates Hippocampal BDNF Expression in Ovariectomized Mice[J]. 神经药理学报, 2013, 3(2): 13-25.

YAO Guang-Yin, JI Dan-Yang, ZHOU Wei-Dong, YAO Hai-Yan, KU Bao-Shan, YANG Dong-Hui.Secoisolariciresinol Reduces Behavioral Despair and Regulates Hippocampal BDNF Expression in Ovariectomized Mice[J]. Acta Neuropharmacologica, 2013, 3(2): 13-25.

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Secoisolariciresinol Reduces Behavioral Despair and Regulates Hippocampal BDNF Expression in Ovariectomized Mice

Secoisolariciresinol Reduces Behavioral Despair and Regulates Hippocampal BDNF Expression in Ovariectomized Mice

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