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 (2): 298-305.doi: 10.4103/1673-5374.244792

• 原著:脑损伤修复保护与再生 • 上一篇    下一篇

天敌应激诱导成年雄性小鼠发生抑郁与神经再生的抑制有关

  

  • 出版日期:2019-02-15 发布日期:2019-02-15
  • 基金资助:

    国家自然科学基金资助，编号：81473115，81622050；广东省自然科学基金(杰出青年学者)，编号：2017A030306004；中国广东省青年顶尖人才支持项目，编号：2016TQ03R586。

 Predator stress-induced depression is associated with inhibition of hippocampal neurogenesis in adult male mice

Yan-Ping Wu 1, 2 , Hua-Ying Gao 1, 2 , Shu-Hua Ouyang 1, 2 , Hiroshi Kurihara 1, 2 , Rong-Rong He 1, 2 , Yi-Fang Li 1, 2   

  1. 1 Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, College of Pharmacy, Jinan University, Guangzhou, China
    2 Anti-Stress and Health Research Center, College of Pharmacy, Jinan University, Guangzhou, Guangdong Province, China
  • Online:2019-02-15 Published:2019-02-15
  • Contact: Yi-Fang Li, PhD, liyifang706@jnu.edu.cn; Rong-Rong He, PhD, rongronghe@jnu.edu.cn.
  • Supported by:

    This study was supported by the National Natural Science Foundation of China, No. 81473115 (to RRH), 81622050 (to RRH); the Natural Science Foundation of Guangdong Province of China for Distinguished Young Scholars, No. 2017A030306004 (to YFL); the Youth Top-Notch Talent Support Program of Guangdong Province of China, No. 2016TQ03R586 (to YFL).

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摘要：

天敌应激是与现实社会心理应激较相似的一种应激模型。因此，实验利用猫应激模型和猫气味应激模型来观察天敌应激对小鼠抑郁症和海马神经再生的影响。实验设计将小鼠经过12 d的猫应激或猫气味应激处理后，利用旷场试验、高架十字迷宫试验和避暗试验评价其行为学变化，利用高效液相电化学方法检测猫应激对小鼠海马中5-羟色胺和5-羟吲哚色胺水平的影响，同时用BrdU(新生细胞标记物)和DCX(未成熟神经元标记物)双重免疫染色评价小鼠海马神经元的增殖情况。结果发现，猫应激或猫气味应激均可诱导成年小鼠抑郁行为的产生，但猫应激具有更明显的效果。猫应激可显著降低小鼠海马5-羟色胺水平，提高海马5-羟吲哚乙酸水平。猫应激后小鼠齿状回BrdU/DCX阳性标记细胞数明显减少，而采用抗抑郁药物氟西汀干预能显著逆转上述全部结果指标的变化。从而表明，天敌应激诱导的抑郁行为和与海马神经再生的抑制有关。

orcid: 0000-0001-5505-5672(Rong-Rong He)
           0000-0002-3356-3702(Yi-Fang Li)

关键词: 抑郁症, 猫应激, 猫气味应激, 行为学评价, 旷场试验, 高架十字迷宫试验, 避暗试验, 5-羟色胺, 5-羟吲哚乙酸, 海马神经再生

Abstract:

Stress has been suggested to disturb the 5-hydroxytryptamine system and decrease neurogenesis, which contribute to the development of depression. Few studies have investigated the effect of predator stress, a type of psychological stress, on depression and hippocampal neurogenesis in adult mice; we therefore investigated this in the present study. A total of 35 adult male Kunming mice were allocated to a cat stress group, cat odor stress group, cat stress + fluoxetine group, cat odor stress + fluoxetine group, or a control group (no stress/treat¬ment). After 12 days of cat stress or cat odor stress, behavioral correlates of depression were measured using the open field test, elevated plus maze test, and dark-avoidance test. The concentrations of hippocampal 5-hydroxytryptamine and 5-hydroxyindoleacetic acid were measured using high-performance liquid chromatography-electrochemical detection. Neurogenesis was also analyzed using a bromode¬oxyuridine and doublecortin double-immunostaining method. Cat stress and cat odor stress induced depression-like behaviors; this effect was stronger in the cat stress model. Furthermore, compared with the control group, cat stress mice exhibited lower 5-hydroxytryptamine concentrations, higher 5-hydroxyindoleacetic acid concentrations, and significantly fewer bromodeoxyuridine+/doublecortin+-labeled cells in the dentate gyrus, which was indicative of less neurogenesis. The changes observed in the cat stress group were not seen in the cat stress + fluoxetine group, which suggests that the effects of predator stress on depression and neurogenesis were reversed by fluoxetine. Taken together, our results indicate that depression-like behaviors induced by predator stress are associated with the inhibition of hippocampal neurogenesis.

Key words: nerve regeneration, depressive disorder, cat stress, cat odor stress, behavioral evaluation, open field test, elevated plus maze test, dark-avoidance test, 5-hydroxytryptamine, 5-hydroxyindoleacetic acid, hippocampal neurogenesis, neural regeneration