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Journal of Integrative Neuroscience  2019, Vol. 18 Issue (1): 43-49    DOI: 10.31083/j.jin.2019.01.116
Original Research Previous articles | Next articles
Promoting neurogenesis in hippocampal dentate gyrus of chronic unpredictable stress-induced depressive-like rats with paeoniflorin
Li-Bing Chen1, #, Feng-Mei Qiu1, #, Xiao-Ming Zhong1, Cheng Hong1, Zhen Huang1, *()
1College of Pharmacy, Zhejiang Chinese Medical University, 311402, Zhejiang, China
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Abstract  

Hippocampal neurogenesis plays an important role in the onset and treatment of depressive disorders. Previous studies suggest that paeoniflorin could be used as an antidepressant for treating rats subjected to chronic unpredictable stress. In this study, the effects of paeoniflorin on neurogenesis in the hippocampus dentate gyrus and potential mechanism of action are further investigated in chronic unpredictable stress-induced rat. Results suggest that paeoniflorin markedly increased both sucrose consumption and the number of 5-bromo-2-deoxyuridine-positive cells in the dentate gyrus of chronic unpredictable stress-induced rats, and the ratio of co-expressed 5-bromo-2-deoxyuridine and glial fibrillary acidic protein-positive cells, but exerted no significant effect on the ratio of co-expressed 5-bromo-2-deoxyuridine and neuronal nuclei-positive cells. Compared with the vehicle group, a significant increase was detected in the number of brain-derived neurotrophic factor-positive cells and the expression of brain-derived neurotrophic factor mRNA in the hippocampus of the paeoniflorin-treated group. According to the results, paeoniflorin promoted neural stem cell proliferation, their differentiation into astrocytes, and neurogenesis in the hippocampal dentate gyrus of chronic unpredictable stress-induced rats. Apart from enhancing the protein expression and gene transcription of brain-derived neurotrophic factor, it also activated the expression of tropomyosin receptor kinase B (a high-affinity receptor of brain-derived neurotrophic factor). This suggests that paeoniflorin might promote neurogenesis in the hippocampus dentate gyrus of chronic unpredictable stress-induced rats and act as an antidepressant by regulating the brain-derived neurotrophic factor-tropomyosin receptor kinase B signaling pathway.

Key words:  Paeoniflorin      antidepressant      chronic unpredictable stress      neurogenesis      dentate gyrus      BDNF-TrkB signaling pathway     
Submitted:  09 November 2018      Accepted:  18 March 2019      Published:  30 March 2019     
Fund: 
  • Y201328806/Zhejiang Education Department Research Project
  • LQ14H280005 to FQ, Q14H280023 to HZ/Zhejiang Provincial Natural Science Foundation
  • 81573643 to HZ, 81503274 to FQ/National Natural Science Foundation of China
*Corresponding Author(s):  Zhen Huang     E-mail:  huangzhen@zcmu.edu.cn
# These authors contributed equally.

Cite this article: 

Li-Bing Chen, Feng-Mei Qiu, Xiao-Ming Zhong, Cheng Hong, Zhen Huang. Promoting neurogenesis in hippocampal dentate gyrus of chronic unpredictable stress-induced depressive-like rats with paeoniflorin. Journal of Integrative Neuroscience, 2019, 18(1): 43-49.

URL: 

https://jin.imrpress.com/EN/10.31083/j.jin.2019.01.116     OR     https://jin.imrpress.com/EN/Y2019/V18/I1/43

Figure 1.  Chronological description of experiment protocols.

Figure 2.  Effect of paeoniflorin and imipramine on percentage of sucrose consumption in CUS-exposed rats (mean $\pm$ SEM, eight rats per group). *p < 0.05 vs. Control-saline group. $^{\#}$p < 0.05, $^{\#\#}$p < 0.01 vs. CUS-saline group.

Figure 3.  Effect of paeoniflorin and imipramine on BrdU immunofluoroscent staining in DG regions of CUS subjects (mean $\pm$ SEM, five rats per group). (A) Control-Saline, (B) CUS-Saline, (C) CUS-Paeoniflorin, (D) CUS-Imipramine. BrdU (red). Scale bar 50 $\mu$m. (E) Number of BrdU-labelled cells in DG region of CUS subjects. *p < 0.05 vs. Control-saline group. $^{\#\#}$p < 0.01 vs. CUS-saline group.

Figure 4.  Effect of paeoniflorin and imipramine on BrdU/GFAP double immunofluoroscent staining in the DG region of hippocampus in CUS subjects (mean $\pm$ SEM, five rats per group). (A) CUS-Imipramine, (B) CUS-Saline, (C) CUS-Paeoniflorin, (D) Control-Saline in the corresponding areas of the hippocampus. BrdU (red), GFAP (green). White arrow: New astrocyte-like cell. Scale bar 20 $\mu$m. (E) Percentage of BrdU+/GFAP+ cells in the DG region of CUS subjects. *p < 0.05 vs. Control-saline group. $^{\#}$p < 0.05 vs. CUS-saline group.

Figure 5.  Effect of paeoniflorin and imipramine on BrdU/ NeuN double immunofluoroscent staining in DG region of hippocampus in CUS subjects (mean ± SEM, five rats per group). (A) Control-Saline, (B) CUS-Saline, (C) CUS-Paeoniflorin, (D) CUS-Imipramine in corresponding areas of hippocampus. BrdU (red), NeuN (green). White arrow: Newly granular neuron-like cell. Scale bar 50 $\mu$m. (E) Percentage of BrdU+/NeuN+ cells in the DG region of CUS subjets. There were no significant differences vs. the CUS-saline group.

Figure 6.  Effect of paeoniflorin and imipramine on level of BDNF protein in hippocampus of CUS subjects (mean ± SEM, five rats per group). (A) Control-Saline, (B) CUS-Saline, (C) CUS-Paeoniflorin, (D) CUS-Imipramine. Scale bar 20 $\mu$m. (E) Effect of paeoniflorin and imipramine on hippocampal BDNF positive cells in CUS subjects. White arrow: BDNF positive cell. *p < 0.05 vs. Control-saline group. $^{\#}$p < 0.05 vs. CUS-saline group.

Figure 7.  Effect of paeoniflorin and imipramine on BDNF mRNA level in hippocampus of CUS subjects (mean ± SEM, three rats per group). **p < 0.01 vs. Control-saline group. $^{\#}$p < 0.05 vs. CUS-saline group.

Figure 8.  Effect of paeoniflorin and imipramine on TrkB immunohistochemical staining in DG region of CUS subjects (mean ± SEM, five rats per group). (A) Control-Saline, (B) CUS-Saline, (C) CUS-Paeoniflorin, (D) CUS-Imipramine. Scale bar 20 $\mu$m. (E) Effect of paeoniflorin and imipramine on hippocampal TrkB level in CUS subjects. White arrow: TrkB positive cell. *p < 0.05 vs. Control-saline group. $^{\#}$p < 0.05 vs. CUS-saline group.

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