, Volume 235, Issue 1, pp 1–12 | Cite as

Gap junction channels as potential targets for the treatment of major depressive disorder

  • Qian Ren
  • Zhen-Zhen Wang
  • Shi-Feng Chu
  • Cong-Yuan Xia
  • Nai-Hong Chen



Major depressive disorder (MDD) remains a major public health problem worldwide. The association between MDD and the dysfunction of gap junction channels (GJCs) in glial cells, especially astrocytes, is still controversial.


This review provides an overview of the role of astrocyte GJCs in LMDD.


Exposure to chronic unpredictable stress caused a reduction in connexin expression in the rat prefrontal cortex, a result that is consistent with clinical findings reported in postmortem studies of brains from MDD patients. Chronic antidepressant treatment in these rats increased the expression of connexins. However, pharmacological GJC blockade in normal rodents decreased connexin expression and caused depressive-like behaviors. Furthermore, GJC dysfunction affects electrical conductance, metabolic coupling and secondary messengers, and inflammatory responses, which are consistent with current hypotheses on MDD. All these results provide a comprehensive overview of the neurobiology of MDD.


This review supports the hypothesis that the regulation of GJCs between astrocytes could be an underlying mechanism for the therapeutic effect of antidepressants.


Major depressive disorder Gap junction channels Connexin 43 Antidepressants Connexin 43 blockers 



This work was supported by the National Natural Science Foundation of China (81573636, U1402221, 81560663), PUMC Youth Fund (3332016058), the Fundamental Research Funds for the Central Universities (2014RC03, 2016RC350002), CAMS Innovation Fund for Medical Sciences (CIFMS) (2016-I2M-1-004), the Scientific Research Foundation of the Higher Education Institutions of Human Province (15K091), and Beijing Key Laboratory of New Drug Mechanisms and Pharmacological Evaluation Study (BZ0150).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no competing interests.


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2017

Authors and Affiliations

  • Qian Ren
    • 1
  • Zhen-Zhen Wang
    • 1
  • Shi-Feng Chu
    • 1
  • Cong-Yuan Xia
    • 1
  • Nai-Hong Chen
    • 1
    • 2
  1. 1.State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica & Neuroscience CenterChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina
  2. 2.College of PharmacyHunan University of Chinese MedicineChangshaChina

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