Metabolic Brain Disease

, Volume 34, Issue 1, pp 93–101 | Cite as

Gallic acid activates hippocampal BDNF-Akt-mTOR signaling in chronic mild stress

  • Ji-Xiao Zhu
  • Jia-Ling Shan
  • Wei-Qiong Hu
  • Jin-Xiang Zeng
  • Ji-Cheng ShuEmail author
Original Article


Gallic acid (3,4,5-trihydroxybenzoic acid) is a naturally occurring polyphenolic compound. Previous study has shown that gallic acid possessed significant antidepressant-like activity in mice, which was partly mediated by increasing serotonin and catecholamine levels. The main aim of the present study is to investigate the possible effects of gallic acid on brain-derived neurotrophic factor (BDNF) signaling activation. Mice were exposed to chronic mild stress (CMS) and orally administrated with gallic acid for four weeks. The behavioral results showed that gallic acid not only reversed the decreased sucrose preference, but also attenuated the increased immobility time. In addition, gallic acid promoted both the BDNF and p-TrkB levels in the hippocampus induced by CMS. Moreover, the results also demonstrated that the inactivated Akt-mTOR signaling pathway, as well as its downstream effectors induced by CMS was activated again by gallic acid. Last, immunofluorescence detection indicated that gallic acid reversed the newborn neurons inhibition in the dentate gyrus by CMS. In conclusion, these results show that the activation of the hippocampal BDNF-Akt-mTOR signaling is involved in the antidepressant-like effects of gallic acid.


Gallic acid Brain-derived neurotrophic factor (BDNF) Chronic mild stress (CMS) 



The project was supported by grants from the National Natural Science Foundation of China (No. 81660702, No. 81460650).

Compliance with ethical standards

Competing interests

The authors declare that they have no conflicts of interest.


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Ji-Xiao Zhu
    • 1
  • Jia-Ling Shan
    • 1
  • Wei-Qiong Hu
    • 1
  • Jin-Xiang Zeng
    • 1
  • Ji-Cheng Shu
    • 1
    Email author
  1. 1.Research Center of Natural Resources of Chinese Medicinal Materials and Ethnic MedicineJiangxi University of Traditional Chinese MedicineNanchangPeople’s Republic of China

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