Promoting neurogenesis in hippocampal dentate gyrus of chronic unpredictable stress-induced depressive-like rats with paeoniflorin

J Integr Neurosci. 2019 Mar 30;18(1):43-49. doi: 10.31083/j.jin.2019.01.116.

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.

Keywords: BDNF-TrkB signaling pathway; Paeoniflorin; antidepressant; chronic unpredictable stress; dentate gyrus; neurogenesis.

MeSH terms

  • Animals
  • Antidepressive Agents / pharmacology*
  • Brain-Derived Neurotrophic Factor / metabolism
  • Chronic Disease
  • Dentate Gyrus / drug effects*
  • Dentate Gyrus / physiopathology
  • Depressive Disorder / drug therapy*
  • Depressive Disorder / physiopathology
  • Disease Models, Animal
  • Glucosides / pharmacology*
  • Imipramine / pharmacology
  • Male
  • Monoterpenes / pharmacology*
  • Neurogenesis / drug effects*
  • Neurogenesis / physiology
  • RNA, Messenger / metabolism
  • Random Allocation
  • Rats, Sprague-Dawley
  • Receptor, trkB / metabolism
  • Stress, Psychological / drug therapy
  • Stress, Psychological / physiopathology
  • Uncertainty

Substances

  • Antidepressive Agents
  • Bdnf protein, rat
  • Brain-Derived Neurotrophic Factor
  • Glucosides
  • Monoterpenes
  • RNA, Messenger
  • peoniflorin
  • Receptor, trkB
  • Imipramine