Neural Regeneration Research ›› 2019, Vol. 14 ›› Issue (2): 298-305.doi: 10.4103/1673-5374.244792

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 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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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