Cellular and Molecular Neurobiology

, Volume 35, Issue 4, pp 473–482 | Cite as

Role of Hippocampus Mitogen-Activated Protein Kinase Phosphatase-1 mRNA Expression and DNA Methylation in the Depression of the Rats with Chronic Unpredicted Stress

  • Chang-Hong Wang
  • Xiao-Li Zhang
  • Yan Li
  • Guo-Dong Wang
  • Xin-Kai Wang
  • Jiao Dong
  • Qiu-Fen Ning
Original Research


Stressful life events especially the chronic unpredictable stress are the obvious precipitating factors of depression. The biological information transduction in cells plays an important role in the molecular biology mechanism of depression. Mitogen-activated protein kinase phosphatase-1 (MKP-1) regulates the cell physiological activity and involves in the adjustment of neural plasticity, function, and survival. This experiment tried to explore the possible effects of MKP-1 in hippocampus on depression of rats by determining the expression of MKP-1 mRNA and DNA methylation in MKP-1 gene promoter. The animal model was established by chronic unpredictable stress, and evaluated by open-field test and weight changes. All the rats were divided into the sham stimulation, the physiological saline, and the fluoxetine (1.25, 2.50, and 5.00 mg/kg) groups randomly. The expression of MKP-1 mRNA in the hippocampus was measured by RT-PCR and the methylation of MKP-1 promoter DNA was detected by COBRA. The chronic unpredicted stress (1) increased the animal movement scores in open-field test, and fluoxetine could prevent this increasement; (2) increased the body weight, and fluoxetine could not prevent this increasement; and (3) increased MKP-1 mRNA expression in the hippocampus, and fluoxetine could prevent it. However, fluoxetine did not influence the DNA methylation of MKP-1 gene promoter in the hippocampus during the chronic unpredicted stress. MKP-1 in the hippocampus might be involved in the etiology of depression, and DNA methylation of MKP-1 gene promoter in the hippocampus did not related with the depression.


Chronic unpredicted stress Depression Mitogen-activated protein kinase phosphatase-1 DNA methylation Fluoxetine mRNA expression 



We thank many investigators in Department of Clinical Mental Health, the Second Affiliated Hospital of Xinxiang Medical University. This work was supported by Grants from the Medical Technology Foundation of Henan Province (112102310211 and 142300410025), Basic Research of Natural Science Foundation of Henan Province (2009A330009), Cultivate scientific research project funds of Xinxiang Medical College (2013ZD117), Scientific Research Projects of High-level Personnel of Xinxiang Medical University (08BSKYQD-004), and Laboratory for Biological Psychiatry of Henan Province.

Conflict of interest

The authors declare that they have no conflict of interest.


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Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Chang-Hong Wang
    • 1
  • Xiao-Li Zhang
    • 1
  • Yan Li
    • 2
  • Guo-Dong Wang
    • 1
  • Xin-Kai Wang
    • 3
  • Jiao Dong
    • 1
  • Qiu-Fen Ning
    • 1
  1. 1.Department of PsychiatryThe Second Affiliated Hospital of Xinxiang Medical UniversityXinxiangChina
  2. 2.Department of Child and Adolescent, Public Health CollegeZhengzhou UniversityZhengzhouChina
  3. 3.Basic Medical CollegeZhengzhou UniversityZhengzhouChina

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