Advertisement

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

Abstract

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.

Keywords

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

Notes

Acknowledgements

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.

References

  1. Boldrini M, Underwood MD, Hen R, Rosoklija GB, Dwork AJ, John Mann J, Arango V (2009) Antidepressants increase neural progenitor cells in the human hippocampus. Neuropsychopharmacol 34:2376–2389.  https://doi.org/10.1038/npp.2009.75 CrossRefGoogle Scholar
  2. Can OD, Turan N, Demir Ozkay U, Ozturk Y (2017) Antidepressant-like effect of gallic acid in mice: dual involvement of serotonergic and catecholaminergic systems. Life Sci 190:110–117.  https://doi.org/10.1016/j.lfs.2017.09.023 CrossRefPubMedGoogle Scholar
  3. Cao B, Luo Q, Fu Y, du L, Qiu T, Yang X, Chen X, Chen Q, Soares JC, Cho RY, Zhang XY, Qiu H (2018) Predicting individual responses to the electroconvulsive therapy with hippocampal subfield volumes in major depression disorder. Sci Rep 8:5434.  https://doi.org/10.1038/s41598-018-23685-9 CrossRefPubMedPubMedCentralGoogle Scholar
  4. Chandrasekhar Y, Phani Kumar G, Ramya EM, Anilakumar KR (2018) Gallic acid protects 6-OHDA induced neurotoxicity by attenuating oxidative stress in human dopaminergic cell line. Neurochem Res 43:1150–1160.  https://doi.org/10.1007/s11064-018-2530-y CrossRefPubMedGoogle Scholar
  5. Chhillar R, Dhingra D (2013) Antidepressant-like activity of gallic acid in mice subjected to unpredictable chronic mild stress. Fundam Clin Pharmacol 27:409–418.  https://doi.org/10.1111/j.1472-8206.2012.01040.x CrossRefPubMedGoogle Scholar
  6. Corona G, Vauzour D, Hercelin J, Williams CM, Spencer JP (2013) Phenolic acid intake, delivered via moderate champagne wine consumption, improves spatial working memory via the modulation of hippocampal and cortical protein expression/activation. Antioxid Redox Signal 19:1676–1689.  https://doi.org/10.1089/ars.2012.5142 CrossRefPubMedGoogle Scholar
  7. David DJ, Samuels BA, Rainer Q, Wang JW, Marsteller D, Mendez I, Drew M, Craig DA, Guiard BP, Guilloux JP, Artymyshyn RP, Gardier AM, Gerald C, Antonijevic IA, Leonardo ED, Hen R (2009) Neurogenesis-dependent and -independent effects of fluoxetine in an animal model of anxiety/depression. Neuron 62:479–493.  https://doi.org/10.1016/j.neuron.2009.04.017 CrossRefPubMedPubMedCentralGoogle Scholar
  8. Drzyzga LR, Marcinowska A, Obuchowicz E (2009) Antiapoptotic and neurotrophic effects of antidepressants: a review of clinical and experimental studies. Brain Res Bull 79:248–257.  https://doi.org/10.1016/j.brainresbull.2009.03.009 CrossRefPubMedGoogle Scholar
  9. Duman RS, Voleti B (2012) Signaling pathways underlying the pathophysiology and treatment of depression: novel mechanisms for rapid-acting agents. Trends Neurosci 35:47–56.  https://doi.org/10.1016/j.tins.2011.11.004 CrossRefPubMedPubMedCentralGoogle Scholar
  10. Huang EJ, Reichardt LF (2001) Neurotrophins: roles in neuronal development and function. Annu Rev Neurosci 24:677–736.  https://doi.org/10.1146/annurev.neuro.24.1.677 CrossRefPubMedPubMedCentralGoogle Scholar
  11. Jourdi H, Hsu YT, Zhou M, Qin Q, Bi X, Baudry M (2009) Positive AMPA receptor modulation rapidly stimulates BDNF release and increases dendritic mRNA translation. J Neurosci 29:8688–8697.  https://doi.org/10.1523/JNEUROSCI.6078-08.2009 CrossRefPubMedPubMedCentralGoogle Scholar
  12. Kerling A, Kück M, Tegtbur U, Grams L, Weber-Spickschen S, Hanke A, Stubbs B, Kahl KG (2017) Exercise increases serum brain-derived neurotrophic factor in patients with major depressive disorder. J Affect Disord 215:152–155.  https://doi.org/10.1016/j.jad.2017.03.034 CrossRefPubMedGoogle Scholar
  13. Kessler RC, Berglund P, Demler O, Jin R, Koretz D, Merikangas KR, Rush AJ, Walters EE, Wang PS, National Comorbidity Survey Replication (2003) The epidemiology of major depressive disorder: results from the National Comorbidity Survey Replication (NCS-R). Jama 289:3095–3105.  https://doi.org/10.1001/jama.289.23.3095 CrossRefPubMedGoogle Scholar
  14. Kishi T, Yoshimura R, Ikuta T, Iwata N (2017) Brain-derived neurotrophic factor and major depressive disorder: evidence from Meta-analyses. Front Psych 8:308.  https://doi.org/10.3389/fpsyt.2017.00308 CrossRefGoogle Scholar
  15. Li W, Keifer J (2012) Rapid enrichment of presynaptic protein in boutons undergoing classical conditioning is mediated by brain-derived neurotrophic factor. Neuroscience 203:50–58.  https://doi.org/10.1016/j.neuroscience.2011.12.015 CrossRefPubMedGoogle Scholar
  16. Lim DA, Alvarez-Buylla A (2016) The adult ventricular-subventricular zone (V-SVZ) and olfactory bulb (OB) neurogenesis. Cold Spring Harb Perspect Biol 8  https://doi.org/10.1101/cshperspect.a018820
  17. Liu XL, Luo L, Mu RH, Liu BB, Geng D, Liu Q, Yi LT (2015) Fluoxetine regulates mTOR signalling in a region-dependent manner in depression-like mice. Sci Rep 5:16024.  https://doi.org/10.1038/srep16024 CrossRefPubMedPubMedCentralGoogle Scholar
  18. Mattson MP, Maudsley S, Martin B (2004) BDNF and 5-HT: a dynamic duo in age-related neuronal plasticity and neurodegenerative disorders. Trends Neurosci 27:589–594.  https://doi.org/10.1016/j.tins.2004.08.001 CrossRefPubMedGoogle Scholar
  19. McKinnon MC, Yucel K, Nazarov A, MacQueen GM (2009) A meta-analysis examining clinical predictors of hippocampal volume in patients with major depressive disorder. J Psych Neurosci: JPN 34:41–54Google Scholar
  20. Mu RH, Fang XY, Wang SS, Li CF, Chen SM, Chen XM, Liu Q, Li YC, Yi LT (2016) Antidepressant-like effects of standardized gypenosides: involvement of brain-derived neurotrophic factor signaling in hippocampus. Psychopharmacology 233:3211–3221.  https://doi.org/10.1007/s00213-016-4357-z CrossRefPubMedGoogle Scholar
  21. Nagpal K, Singh SK, Mishra DN (2012) Nanoparticle mediated brain targeted delivery of gallic acid: in vivo behavioral and biochemical studies for improved antioxidant and antidepressant-like activity. Drug Deliv 19:378–391.  https://doi.org/10.3109/10717544.2012.738437 CrossRefPubMedGoogle Scholar
  22. Olesen MV, Wortwein G, Folke J, Pakkenberg B (2017) Electroconvulsive stimulation results in long-term survival of newly generated hippocampal neurons in rats. Hippocampus 27:52–60.  https://doi.org/10.1002/hipo.22670 CrossRefPubMedGoogle Scholar
  23. Park SW, Lee JG, Seo MK, Lee CH, Cho HY, Lee BJ, Seol W, Kim YH (2014) Differential effects of antidepressant drugs on mTOR signalling in rat hippocampal neurons. Int J Neuropsychopharmacol 17:1831–1846.  https://doi.org/10.1017/S1461145714000534 CrossRefPubMedGoogle Scholar
  24. Porsolt RD, Bertin A, Jalfre M (1977) Behavioral despair in mice: a primary screening test for antidepressants. Archives Internationales de Pharmacodynamie et de Therapie 229:327–336PubMedGoogle Scholar
  25. Ren Y, Wang JL, Zhang X, Wang H, Ye Y, Song L, Wang YJ, Tu MJ, Wang WW, Yang L, Jiang B (2017) Antidepressant-like effects of ginsenoside Rg2 in a chronic mild stress model of depression. Brain Res Bull 134:211–219.  https://doi.org/10.1016/j.brainresbull.2017.08.009 CrossRefPubMedGoogle Scholar
  26. Rybakowski JK, Permoda-Osip A, Bartkowska-Sniatkowska A (2017) Ketamine augmentation rapidly improves depression scores in inpatients with treatment-resistant bipolar depression. Int J Psychiatry Clin Pract 21:99–103.  https://doi.org/10.1080/13651501.2017.1297834 CrossRefPubMedGoogle Scholar
  27. Santarelli L, Saxe M, Gross C, Surget A, Battaglia F, Dulawa S, Weisstaub N, Lee J, Duman R, Arancio O, Belzung C, Hen R (2003) Requirement of hippocampal neurogenesis for the behavioral effects of antidepressants. Science 301:805–809.  https://doi.org/10.1126/science.1083328 CrossRefPubMedGoogle Scholar
  28. Seib DR, Martin-Villalba A (2015) Neurogenesis in the Normal Ageing Hippocampus: A Mini-Review. Gerontology 61:327–335.  https://doi.org/10.1159/000368575 CrossRefPubMedGoogle Scholar
  29. Stepanichev MY, Tishkina AO, R. Novikova M, Levshina IP, V. Freiman S, V. Onufriev M, Levchenko OA, A. Lazareva N, V. Gulyaeva N (2016) Anhedonia but not passive floating is an indicator of depressive-like behavior in two chronic stress paradigms. Acta Neurobiol Exp 76:324–333Google Scholar
  30. Thakare VN, Patil RR, Oswal RJ, Dhakane VD, Aswar MK, Patel BM (2018) Therapeutic potential of silymarin in chronic unpredictable mild stress induced depressive-like behavior in mice. J Psychopharmacol 32:223–235.  https://doi.org/10.1177/0269881117742666 CrossRefPubMedGoogle Scholar
  31. Warner-Schmidt JL, Duman RS (2006) Hippocampal neurogenesis: opposing effects of stress and antidepressant treatment. Hippocampus 16:239–249.  https://doi.org/10.1002/hipo.20156 CrossRefPubMedGoogle Scholar
  32. Willner P, Towell A, Sampson D, Sophokleous S, Muscat R (1987) Reduction of sucrose preference by chronic unpredictable mild stress, and its restoration by a tricyclic antidepressant. Psychopharmacology 93:358–364CrossRefGoogle Scholar
  33. Yi LT, Li J, Liu BB, Luo L, Liu Q, Geng D (2014) BDNF-ERK-CREB signalling mediates the role of miR-132 in the regulation of the effects of oleanolic acid in male mice. J Psych Neurosci: JPN 39:348–359CrossRefGoogle Scholar
  34. Yi LT, Luo L, Wu YJ, Liu BB, Liu XL, Geng D, Liu Q (2015) Circadian variations in behaviors, BDNF and cell proliferation in depressive mice. Metab Brain Dis 30:1495–1503.  https://doi.org/10.1007/s11011-015-9710-0 CrossRefPubMedGoogle Scholar
  35. Yu JJ, Pei LB, Zhang Y, Wen ZY, Yang JL (2015) Chronic supplementation of curcumin enhances the efficacy of antidepressants in major depressive disorder: a randomized, double-blind, placebo-controlled pilot study. J Clin Psychopharmacol 35:406–410.  https://doi.org/10.1097/JCP.0000000000000352 CrossRefPubMedGoogle Scholar

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

Personalised recommendations