Biomolecules & Therapeutics

The Korean Society of Applied Pharmacology (한국응용약물학회)
권호 표지
DOI QR코드

DOI QR Code

Phytochemicals That Act on Synaptic Plasticity as Potential Prophylaxis against Stress-Induced Depressive Disorder

  • Soojung, Yoon (Department of Health Sciences and Technology, GAIHST, Gachon University) ;
  • Hamid, Iqbal (Department of Microbiology, College of Medicine, Gachon University) ;
  • Sun Mi, Kim (Department of Psychiatry, Chung-Ang University College of Medicine) ;
  • Mirim, Jin (Department of Health Sciences and Technology, GAIHST, Gachon University)
  • Received : 2022.09.01
  • Accepted : 2022.12.20
  • Published : 2023.03.01
Download PDF
⟨ Previous Next ⟩

Abstract

Depression is a neuropsychiatric disorder associated with persistent stress and disruption of neuronal function. Persistent stress causes neuronal atrophy, including loss of synapses and reduced size of the hippocampus and prefrontal cortex. These alterations are associated with neural dysfunction, including mood disturbances, cognitive impairment, and behavioral changes. Synaptic plasticity is the fundamental function of neural networks in response to various stimuli and acts by reorganizing neuronal structure, function, and connections from the molecular to the behavioral level. In this review, we describe the alterations in synaptic plasticity as underlying pathological mechanisms for depression in animal models and humans. We further elaborate on the significance of phytochemicals as bioactive agents that can positively modulate stress-induced, aberrant synaptic activity. Bioactive agents, including flavonoids, terpenes, saponins, and lignans, have been reported to upregulate brain-derived neurotrophic factor expression and release, suppress neuronal loss, and activate the relevant signaling pathways, including TrkB, ERK, Akt, and mTOR pathways, resulting in increased spine maturation and synaptic numbers in the neuronal cells and in the brains of stressed animals. In clinical trials, phytochemical usage is regarded as safe and well-tolerated for suppressing stress-related parameters in patients with depression. Thus, intake of phytochemicals with safe and active effects on synaptic plasticity may be a strategy for preventing neuronal damage and alleviating depression in a stressful life.

Keywords

Acknowledgement

This research was supported by the Bio & Medical Technology Development Program of the National Research Foundation (NRF) funded by the Korean government (MSIT) (No. 2018M3A9C4076473) and the Gachon University Research Fund of 2019 (GCU-2019-0325).

References

  1. Anjomshoa, M., Boroujeni, S. N., Ghasemi, S., Lorigooini, Z., Amiri, A., Balali-Dehkordi, S. and Amini-Khoei, H. (2020) Rutin via increase in the CA3 diameter of the hippocampus exerted antidepressantl-ike effect in mouse model of maternal separation stress: possible involvement of NMDA receptors. Behav. Neurol. 2020, 4813616.
  2. Bengtson, C. P. and Bading, H. (2012) Nuclear calcium signaling. Adv. Exp. Med. Biol. 970, 377-405. https://doi.org/10.1007/978-3-7091-0932-8_17
  3. Bergami, M., Rimondini, R., Santi, S., Blum, R., Gotz, M. and Canossa, M. (2008) Deletion of TrkB in adult progenitors alters newborn neuron integration into hippocampal circuits and increases anxietylike behavior. Proc. Natl. Acad. Sci. U. S. A. 105, 15570-15575. https://doi.org/10.1073/pnas.0803702105
  4. Bergman, J., Miodownik, C., Bersudsky, Y., Sokolik, S., Lerner, P. P., Kreinin, A., Polakiewicz, J. and Lerner, V. (2013) Curcumin as an add-on to antidepressive treatment: a randomized, double-blind, placebo-controlled, pilot clinical study. Clin. Neuropharmacol. 36, 73-77. https://doi.org/10.1097/WNF.0b013e31828ef969
  5. Bjorkholm, C. and Monteggia, L. M. (2016) BDNF - a key transducer of antidepressant effects. Neuropharmacology 102, 72-79. https://doi.org/10.1016/j.neuropharm.2015.10.034
  6. Carhart-Harris, R. L., Bolstridge, M., Day, C. M. J., Rucker, J., Watts, R., Erritzoe, D. E., Kaelen, M., Giribaldi, B., Bloomfield, M., Pilling, S., Rickard, J. A., Forbes, B., Feilding, A., Taylor, D., Curran, H. V. and Nutt, D. J. (2018) Psilocybin with psychological support for treatment-resistant depression: six-month follow-up. Psychopharmacology (Berl.) 235, 399-408. https://doi.org/10.1007/s00213-017-4771-x
  7. Carvalho, A. F., Sharma, M. S., Brunoni, A. R., Vieta, E. and Fava, G. A. (2016) The safety, tolerability and risks associated with the use of newer generation antidepressant drugs: a critical review of the literature. Psychother. Psychosom. 85, 270-288. https://doi.org/10.1159/000447034
  8. Castren, E. and Kojima, M. (2017) Brain-derived neurotrophic factor in mood disorders and antidepressant treatments. Neurobiol. Dis. 97, 119-126. https://doi.org/10.1016/j.nbd.2016.07.010
  9. Chandrasekar, V. and Dreyer, J. L. (2009) microRNAs miR-124, let-7d and miR-181a regulate cocaine-induced plasticity. Mol. Cell. Neurosci. 42, 350-362. https://doi.org/10.1016/j.mcn.2009.08.009
  10. Chang, H. A., Wang, Y. H., Tung, C. S., Yeh, C. B. and Liu, Y. P. (2016) 7,8-Dihydroxyflavone, a tropomyosin-kinase related receptor B agonist, produces fast-onset antidepressant-like effects in rats exposed to chronic mild stress. Psychiatry Investig. 13, 531-540. https://doi.org/10.4306/pi.2016.13.5.531
  11. Chen, B., Dowlatshahi, D., MacQueen, G. M., Wang, J. F. and Young, L. T. (2001) Increased hippocampal BDNF immunoreactivity in subjects treated with antidepressant medication. Biol. Psychiatry 50, 260-265. https://doi.org/10.1016/S0006-3223(01)01083-6
  12. Chen, L. X., Qi, Z., Shao, Z. J., Li, S. S., Qi, Y. L., Gao, K., Liu, S. X., Li, Z., Sun, Y. S. and Li, P. Y. (2019) Study on antidepressant activity of pseudo-ginsenoside HQ on depression-like behavior in mice. Molecules 24, 870.
  13. Chen, X. Q., Chen, S. J., Liang, W. N., Wang, M., Li, C. F., Wang, S. S., Dong, S. Q., Yi, L. T. and Li, C. D. (2018) Saikosaponin A attenuates perimenopausal depression-like symptoms by chronic unpredictable mild stress. Neurosci. Lett. 662, 283-289. https://doi.org/10.1016/j.neulet.2017.09.046
  14. Chen, Z. Y., Jing, D., Bath, K. G., Ieraci, A., Khan, T., Siao, C. J., Herrera, D. G., Toth, M., Yang, C., McEwen, B. S., Hempstead, B. L. and Lee, F. S. (2006) Genetic variant BDNF (Val66Met) polymorphism alters anxiety-related behavior. Science 314, 140-143. https://doi.org/10.1126/science.1129663
  15. Cholewinski, T., Pereira, D., Moerland, M. and Jacobs, G. E. (2021) MTORC1 signaling as a biomarker in major depressive disorder and its pharmacological modulation by novel rapid-acting antidepressants. Ther. Adv. Psychopharmacol. 11, 20451253211036814.
  16. Citri, A. and Malenka, R. C. (2008) Synaptic plasticity: multiple forms, functions, and mechanisms. Neuropsychopharmacology 33, 18-41. https://doi.org/10.1038/sj.npp.1301559
  17. Cramer, S. C., Sur, M., Dobkin, B. H., O'Brien, C., Sanger, T. D., Trojanowski, J. Q., Rumsey, J. M., Hicks, R., Cameron, J., Chen, D., Chen, W. G., Cohen, L. G., deCharms, C., Duffy, C. J., Eden, G. F., Fetz, E. E., Filart, R., Freund, M., Grant, S. J., Haber, S., Kalivas, P. W., Kolb, B., Kramer, A. F., Lynch, M., Mayberg, H. S., McQuillen, P. S., Nitkin, R., Pascual-Leone, A., Reuter-Lorenz, P., Schiff, N., Sharma, A., Shekim, L., Stryker, M., Sullivan, E. V. and Vinogradov, S. (2011) Harnessing neuroplasticity for clinical applications. Brain 134, 1591-1609. https://doi.org/10.1093/brain/awr039
  18. Davinelli, S., Scapagnini, G., Marzatico, F., Nobile, V., Ferrara, N. and Corbi, G. (2017) Influence of equol and resveratrol supplementation on health-related quality of life in menopausal women: a randomized, placebo-controlled study. Maturitas 96, 77-83. https://doi.org/10.1016/j.maturitas.2016.11.016
  19. Davis, A. K., Barrett, F. S., May, D. G., Cosimano, M. P., Sepeda, N. D., Johnson, M. W., Finan, P. H. and Griffiths, R. R. (2021) Effects of Psilocybin-assisted therapy on major depressive disorder: a randomized clinical trial. JAMA Psychiatry 78, 481-489. https://doi.org/10.1001/jamapsychiatry.2020.3285
  20. Duman, C. H., Schlesinger, L., Kodama, M., Russell, D. S. and Duman, R. S. (2007) A role for MAP kinase signaling in behavioral models of depression and antidepressant treatment. Biol. Psychiatry 61, 661-670. https://doi.org/10.1016/j.biopsych.2006.05.047
  21. Duman, R. S. and Aghajanian, G. K. (2012) Synaptic dysfunction in depression: potential therapeutic targets. Science 338, 68-72. https://doi.org/10.1126/science.1222939
  22. Duman, R. S., Aghajanian, G. K., Sanacora, G. and Krystal, J. H. (2016) Synaptic plasticity and depression: new insights from stress and rapid-acting antidepressants. Nat. Med. 22, 238-249. https://doi.org/10.1038/nm.4050
  23. Duman, R. S. and Monteggia, L. M. (2006) A neurotrophic model for stress-related mood disorders. Biol. Psychiatry 59, 1116-1127. https://doi.org/10.1016/j.biopsych.2006.02.013
  24. Duric, V., Banasr, M., Stockmeier, C. A., Simen, A. A., Newton, S. S., Overholser, J. C., Jurjus, G. J., Dieter, L. and Duman, R. S. (2013) Altered expression of synapse and glutamate related genes in post-mortem hippocampus of depressed subjects. Int. J. Neuropsychopharmacol. 16, 69-82. https://doi.org/10.1017/s1461145712000016
  25. Egan, M. F., Kojima, M., Callicott, J. H., Goldberg, T. E., Kolachana, B. S., Bertolino, A., Zaitsev, E., Gold, B., Goldman, D., Dean, M., Lu, B. and Weinberger, D. R. (2003) The BDNF val66met polymorphism affects activity-dependent secretion of BDNF and human memory and hippocampal function. Cell 112, 257-269. https://doi.org/10.1016/S0092-8674(03)00035-7
  26. Emili, M., Guidi, S., Uguagliati, B., Giacomini, A., Bartesaghi, R. and Stagni, F. (2022) Treatment with the flavonoid 7,8-Dihydroxyflavone: a promising strategy for a constellation of body and brain disorders. Crit. Rev. Food Sci. Nutr. 62, 13-50. https://doi.org/10.1080/10408398.2020.1810625
  27. Fan, C., Song, Q., Wang, P., Li, Y., Yang, M. and Yu, S. Y. (2018a) Neuroprotective effects of ginsenoside-Rg1 against depression-like behaviors via suppressing glial activation, synaptic deficits, and neuronal apoptosis in rats. Front. Immunol. 9, 2889.
  28. Fan, C., Zhu, X., Song, Q., Wang, P., Liu, Z. and Yu, S. Y. (2018b) MiR-134 modulates chronic stress-induced structural plasticity and depression-like behaviors via downregulation of Limk1/cofilin signaling in rats. Neuropharmacology 131, 364-376. https://doi.org/10.1016/j.neuropharm.2018.01.009
  29. Fang, K., Li, H. R., Chen, X. X., Gao, X. R., Huang, L. L., Du, A. Q., Jiang, C., Li, H. and Ge, J. F. (2019) Quercetin alleviates LPS-induced depression-like behavior in rats via regulating BDNF-related imbalance of copine 6 and TREM1/2 in the hippocampus and PFC. Front. Pharmacol. 10, 1544. https://doi.org/10.3389/fphar.2019.01544
  30. Fremeau, R. T., Jr., Kam, K., Qureshi, T., Johnson, J., Copenhagen, D. R., Storm-Mathisen, J., Chaudhry, F. A., Nicoll, R. A. and Edwards, R. H. (2004) Vesicular glutamate transporters 1 and 2 target to functionally distinct synaptic release sites. Science 304, 1815-1819. https://doi.org/10.1126/science.1097468
  31. Fu, H., Liu, L., Tong, Y., Li, Y., Zhang, X., Gao, X., Yong, J., Zhao, J., Xiao, D., Wen, K. and Wang, H. (2019) The antidepressant effects of hesperidin on chronic unpredictable mild stress-induced mice. Eur. J. Pharmacol. 853, 236-246. https://doi.org/10.1016/j.ejphar.2019.03.035
  32. Fusar-Poli, L., Vozza, L., Gabbiadini, A., Vanella, A., Concas, I., Tinacci, S., Petralia, A., Signorelli, M. S. and Aguglia, E. (2020) Curcumin for depression: a meta-analysis. Crit. Rev. Food Sci. Nutr. 60, 2643-2653. https://doi.org/10.1080/10408398.2019.1653260
  33. Gao, Y. N., Zhang, Y. Q., Wang, H., Deng, Y. L. and Li, N. M. (2022) A new player in depression: MiRNAs as modulators of altered synaptic plasticity. Int. J. Mol. Sci. 23, 4555.
  34. GBD 2017 Disease and Injury Incidence and Prevalence Collaborators (2018) Global, regional, and national incidence, prevalence, and years lived with disability for 354 diseases and injuries for 195 countries and territories, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet 392, 1789-1858. https://doi.org/10.1016/s0140-6736(18)32279-7
  35. Ghazizadeh-Hashemi, F., Bagheri, S., Ashraf-Ganjouei, A., Moradi, K., Shahmansouri, N., Mehrpooya, M., Noorbala, A. A. and Akhondzadeh, S. (2021) Efficacy and safety of sulforaphane for treatment of mild to moderate depression in patients with history of cardiac interventions: a randomized, double-blind, placebo-controlled clinical trial. Psychiatry Clin. Neurosci. 75, 250-255. https://doi.org/10.1111/pcn.13276
  36. Goswami, D. B., Jernigan, C. S., Chandran, A., Iyo, A. H., May, W. L., Austin, M. C., Stockmeier, C. A. and Karolewicz, B. (2013) Gene expression analysis of novel genes in the prefrontal cortex of major depressive disorder subjects. Prog. Neuropsychopharmacol. Biol. Psychiatry 43, 126-133. https://doi.org/10.1016/j.pnpbp.2012.12.010
  37. Gourley, S. L., Kedves, A. T., Olausson, P. and Taylor, J. R. (2009) A history of corticosterone exposure regulates fear extinction and cortical NR2B, GluR2/3, and BDNF. Neuropsychopharmacology 34, 707-716. https://doi.org/10.1038/npp.2008.123
  38. Greicius, M. D., Flores, B. H., Menon, V., Glover, G. H., Solvason, H. B., Kenna, H., Reiss, A. L. and Schatzberg, A. F. (2007) Resting-state functional connectivity in major depression: abnormally increased contributions from subgenual cingulate cortex and thalamus. Biol. Psychiatry 62, 429-437. https://doi.org/10.1016/j.biopsych.2006.09.020
  39. Guilloux, J. P., Douillard-Guilloux, G., Kota, R., Wang, X., Gardier, A. M., Martinowich, K., Tseng, G. C., Lewis, D. A. and Sibille, E. (2012) Molecular evidence for BDNF- and GABA-related dysfunctions in the amygdala of female subjects with major depression. Mol. Psychiatry 17, 1130-1142. https://doi.org/10.1038/mp.2011.113
  40. Han, J., Wang, D. S., Liu, S. B. and Zhao, M. G. (2016) Cytisine, a partial agonist of alpha4beta2 nicotinic acetylcholine receptors, reduced unpredictable chronic mild stress-induced depression-like behaviors. Biomol. Ther. (Seoul) 24, 291-297. https://doi.org/10.4062/biomolther.2015.113
  41. Hesselgrave, N., Troppoli, T. A., Wulff, A. B., Cole, A. B. and Thompson, S. M. (2021) Harnessing psilocybin: antidepressant-like behavioral and synaptic actions of psilocybin are independent of 5-HT2R activation in mice. Proc. Natl. Acad. Sci. U. S. A. 118, e2022489118.
  42. Hu, M. Z., Wang, A. R., Zhao, Z. Y., Chen, X. Y., Li, Y. B. and Liu, B. (2019) Antidepressant-like effects of paeoniflorin on post-stroke depression in a rat model. Neurol. Res. 41, 446-455. https://doi.org/10.1080/01616412.2019.1576361
  43. Hu, X., Ballo, L., Pietila, L., Viesselmann, C., Ballweg, J., Lumbard, D., Stevenson, M., Merriam, E. and Dent, E. W. (2011) BDNF-induced increase of PSD-95 in dendritic spines requires dynamic microtubule invasions. J. Neurosci. 31, 15597-15603. https://doi.org/10.1523/JNEUROSCI.2445-11.2011
  44. Hurley, L. L., Akinfiresoye, L., Nwulia, E., Kamiya, A., Kulkarni, A. A. and Tizabi, Y. (2013) Antidepressant-like effects of curcumin in WKY rat model of depression is associated with an increase in hippocampal BDNF. Behav. Brain Res. 239, 27-30. https://doi.org/10.1016/j.bbr.2012.10.049
  45. Ignacio, Z. M., Reus, G. Z., Arent, C. O., Abelaira, H. M., Pitcher, M. R. and Quevedo, J. (2016) New perspectives on the involvement of mTOR in depression as well as in the action of antidepressant drugs. Br. J. Clin. Pharmacol. 82, 1280-1290. https://doi.org/10.1111/bcp.12845
  46. Im, H. I. and Kenny, P. J. (2012) MicroRNAs in neuronal function and dysfunction. Trends Neurosci. 35, 325-334. https://doi.org/10.1016/j.tins.2012.01.004
  47. Jernigan, C. S., Goswami, D. B., Austin, M. C., Iyo, A. H., Chandran, A., Stockmeier, C. A. and Karolewicz, B. (2011) The mTOR signaling pathway in the prefrontal cortex is compromised in major depressive disorder. Prog. Neuropsychopharmacol. Biol. Psychiatry 35, 1774-1779. https://doi.org/10.1016/j.pnpbp.2011.05.010
  48. Ji, Y., Lu, Y., Yang, F., Shen, W., Tang, T. T., Feng, L., Duan, S. and Lu, B. (2010) Acute and gradual increases in BDNF concentration elicit distinct signaling and functions in neurons. Nat. Neurosci. 13, 302-309. https://doi.org/10.1038/nn.2505
  49. Jiang, B., Huang, C., Chen, X. F., Tong, L. J. and Zhang, W. (2015) Tetramethylpyrazine produces antidepressant-like effects in mice through promotion of BDNF signaling pathway. Int. J. Neuropsychopharmacol. 18, pyv010.
  50. Kanchanatawan, B., Tangwongchai, S., Sughondhabhirom, A., Suppapitiporn, S., Hemrunrojn, S., Carvalho, A. F. and Maes, M. (2018) Add-on treatment with curcumin has antidepressive effects in Thai patients with major depression: results of a randomized doubleblind placebo-controlled study. Neurotox. Res. 33, 621-633. https://doi.org/10.1007/s12640-017-9860-4
  51. Kang, H. J., Voleti, B., Hajszan, T., Rajkowska, G., Stockmeier, C. A., Licznerski, P., Lepack, A., Majik, M. S., Jeong, L. S., Banasr, M., Son, H. and Duman, R. S. (2012) Decreased expression of synapse-related genes and loss of synapses in major depressive disorder. Nat. Med. 18, 1413-1417. https://doi.org/10.1038/nm.2886
  52. Kasai, H., Fukuda, M., Watanabe, S., Hayashi-Takagi, A. and Noguchi, J. (2010) Structural dynamics of dendritic spines in memory and cognition. Trends Neurosci. 33, 121-129. https://doi.org/10.1016/j.tins.2010.01.001
  53. Kew, J. N. and Kemp, J. A. (2005) Ionotropic and metabotropic glutamate receptor structure and pharmacology. Psychopharmacology (Berl.) 179, 4-29. https://doi.org/10.1007/s00213-005-2200-z
  54. Ko, S., Jang, W. S., Jeong, J. H., Ahn, J. W., Kim, Y. H., Kim, S., Chae, H. K. and Chung, S. (2021) (-)-Gallocatechin gallate from green tea rescues cognitive impairment through restoring hippocampal silent synapses in post-menopausal depression. Sci. Rep. 11, 910.
  55. Krishnan, V. and Nestler, E. J. (2008) The molecular neurobiology of depression. Nature 455, 894-902. https://doi.org/10.1038/nature07455
  56. Li, C. F., Chen, S. M., Chen, X. M., Mu, R. H., Wang, S. S., Geng, D., Liu, Q. and Yi, L. T. (2016) ERK-dependent brain-derived neurotrophic factor regulation by hesperidin in mice exposed to chronic mild stress. Brain Res. Bull. 124, 40-47. https://doi.org/10.1016/j.brainresbull.2016.03.016
  57. Li, H. Y., Zhao, Y. H., Zeng, M. J., Fang, F., Li, M., Qin, T. T., Ye, L. Y., Li, H. W., Qu, R. and Ma, S. P. (2017) Saikosaponin D relieves unpredictable chronic mild stress induced depressive-like behavior in rats: involvement of HPA axis and hippocampal neurogenesis. Psychopharmacology (Berl.) 234, 3385-3394. https://doi.org/10.1007/s00213-017-4720-8
  58. Li, J., Zhou, Y., Liu, B. B., Liu, Q., Geng, D., Weng, L. J. and Yi, L. T. (2013) Nobiletin ameliorates the deficits in hippocampal BDNF, TrkB, and synapsin I induced by chronic unpredictable mild stress. Evid. Based Complement. Alternat. Med. 2013, 359682.
  59. Li, N., Lee, B., Liu, R. J., Banasr, M., Dwyer, J. M., Iwata, M., Li, X. Y., Aghajanian, G. and Duman, R. S. (2010) mTOR-dependent synapse formation underlies the rapid antidepressant effects of NMDA antagonists. Science 329, 959-964. https://doi.org/10.1126/science.1190287
  60. Liu, C., Chan, C. B. and Ye, K. (2016a) 7,8-dihydroxy-flavone, a small molecular TrkB agonist, is useful for treating various BDNF-implicated human disorders. Transl. Neurodegener. 5, 2.
  61. Liu, D., Wang, Z., Gao, Z., Xie, K., Zhang, Q., Jiang, H. and Pang, Q. (2014) Effects of curcumin on learning and memory deficits, BDNF, and ERK protein expression in rats exposed to chronic unpredictable stress. Behav. Brain Res. 271, 116-121. https://doi.org/10.1016/j.bbr.2014.05.068
  62. Liu, R. J., Lee, F. S., Li, X. Y., Bambico, F., Duman, R. S. and Aghajanian, G. K. (2012) Brain-derived neurotrophic factor Val66Met allele impairs basal and ketamine-stimulated synaptogenesis in prefrontal cortex. Biol. Psychiatry 71, 996-1005. https://doi.org/10.1016/j.biopsych.2011.09.030
  63. Liu, S., Li, T., Liu, H., Wang, X., Bo, S., Xie, Y., Bai, X., Wu, L., Wang, Z. and Liu, D. (2016b) Resveratrol exerts antidepressant properties in the chronic unpredictable mild stress model through the regulation of oxidative stress and mTOR pathway in the rat hippocampus and prefrontal cortex. Behav. Brain Res. 302, 191-199. https://doi.org/10.1016/j.bbr.2016.01.037
  64. Liu, W., Wu, J., Huang, J., Zhuo, P., Lin, Y., Wang, L., Lin, R., Chen, L. and Tao, J. (2017) Electroacupuncture regulates hippocampal synaptic plasticity via miR-134-mediated LIMK1 function in rats with ischemic stroke. Neural Plast. 2017, 9545646.
  65. Liu, Z., Qi, Y., Cheng, Z., Zhu, X., Fan, C. and Yu, S. Y. (2016c) The effects of ginsenoside Rg1 on chronic stress induced depression-like behaviors, BDNF expression and the phosphorylation of PKA and CREB in rats. Neuroscience 322, 358-369. https://doi.org/10.1016/j.neuroscience.2016.02.050
  66. Lopresti, A. L. and Drummond, P. D. (2017) Efficacy of curcumin, and a saffron/curcumin combination for the treatment of major depression: a randomised, double-blind, placebo-controlled study. J. Affect. Disord. 207, 188-196. https://doi.org/10.1016/j.jad.2016.09.047
  67. Lopresti, A. L., Maes, M., Meddens, M. J., Maker, G. L., Arnoldussen, E. and Drummond, P. D. (2015) Curcumin and major depression: a randomised, double-blind, placebo-controlled trial investigating the potential of peripheral biomarkers to predict treatment response and antidepressant mechanisms of change. Eur. Neuropsychopharmacol. 25, 38-50. https://doi.org/10.1016/j.euroneuro.2014.11.015
  68. Lu, C., Gao, R., Zhang, Y., Jiang, N., Chen, Y., Sun, J., Wang, Q., Fan, B., Liu, X. and Wang, F. (2021) S-equol, a metabolite of dietary soy isoflavones, alleviates lipopolysaccharide-induced depressive-like behavior in mice by inhibiting neuroinflammation and enhancing synaptic plasticity. Food Funct. 12, 5770-5778. https://doi.org/10.1039/D1FO00547B
  69. Luo, L., Hensch, T. K., Ackerman, L., Barbel, S., Jan, L. Y. and Jan, Y. N. (1996) Differential effects of the Rac GTPase on Purkinje cell axons and dendritic trunks and spines. Nature 379, 837-840. https://doi.org/10.1038/379837a0
  70. MacQueen, G. and Frodl, T. (2011) The hippocampus in major depression: evidence for the convergence of the bench and bedside in psychiatric research? Mol. Psychiatry 16, 252-264. https://doi.org/10.1038/mp.2010.80
  71. MacQueen, G. M., Yucel, K., Taylor, V. H., Macdonald, K. and Joffe, R. (2008) Posterior hippocampal volumes are associated with remission rates in patients with major depressive disorder. Biol. Psychiatry 64, 880-883. https://doi.org/10.1016/j.biopsych.2008.06.027
  72. Martins, H. C. and Schratt, G. (2021) MicroRNA-dependent control of neuroplasticity in affective disorders. Transl. Psychiatry 11, 263.
  73. Milne, A. M., MacQueen, G. M. and Hall, G. B. (2012) Abnormal hippocampal activation in patients with extensive history of major depression: an fMRI study. J. Psychiatry Neurosci. 37, 28-36. https://doi.org/10.1503/jpn.110004
  74. Ng, Q. X., Koh, S. S. H., Chan, H. W. and Ho, C. Y. X. (2017) Clinical use of curcumin in depression: a meta-analysis. J. Am. Med. Dir. Assoc. 18, 503-508. https://doi.org/10.1016/j.jamda.2016.12.071
  75. Olde Loohuis, N. F., Ba, W., Stoerchel, P. H., Kos, A., Jager, A., Schratt, G., Martens, G. J., van Bokhoven, H., Nadif Kasri, N. and Aschrafi, A. (2015) MicroRNA-137 controls AMPA-receptor-mediated transmission and mGluR-dependent LTD. Cell Rep. 11, 1876-1884. https://doi.org/10.1016/j.celrep.2015.05.040
  76. Ota, K. T., Liu, R. J., Voleti, B., Maldonado-Aviles, J. G., Duric, V., Iwata, M., Dutheil, S., Duman, C., Boikess, S., Lewis, D. A., Stockmeier, C. A., DiLeone, R. J., Rex, C., Aghajanian, G. K. and Duman, R. S. (2014) REDD1 is essential for stress-induced synaptic loss and depressive behavior. Nat. Med. 20, 531-535. https://doi.org/10.1038/nm.3513
  77. Park, H. and Poo, M. M. (2013) Neurotrophin regulation of neural circuit development and function. Nat. Rev. Neurosci. 14, 7-23. https://doi.org/10.1038/nrn3379
  78. Patterson, M. and Yasuda, R. (2011) Signalling pathways underlying structural plasticity of dendritic spines. Br. J. Pharmacol. 163, 1626-1638. https://doi.org/10.1111/j.1476-5381.2011.01328.x
  79. Perluigi, M., Di Domenico, F. and Butterfield, D. A. (2015) mTOR signaling in aging and neurodegeneration: at the crossroad between metabolism dysfunction and impairment of autophagy. Neurobiol. Dis. 84, 39-49. https://doi.org/10.1016/j.nbd.2015.03.014
  80. Popoli, M., Yan, Z., McEwen, B. S. and Sanacora, G. (2011) The stressed synapse: the impact of stress and glucocorticoids on glutamate transmission. Nat. Rev. Neurosci. 13, 22-37. https://doi.org/10.1038/nrn3138
  81. Radley, J., Morilak, D., Viau, V. and Campeau, S. (2015) Chronic stress and brain plasticity: mechanisms underlying adaptive and maladaptive changes and implications for stress-related CNS disorders. Neurosci. Biobehav. Rev. 58, 79-91. https://doi.org/10.1016/j.neubiorev.2015.06.018
  82. Rajan, S., McKee, M., Rangarajan, S., Bangdiwala, S., Rosengren, A., Gupta, R., Kutty, V. R., Wielgosz, A., Lear, S., AlHabib, K. F., Co, H. U., Lopez-Jaramillo, P., Avezum, A., Seron, P., Oguz, A., Kruger, I. M., Diaz, R., Nafiza, M. N., Chifamba, J., Yeates, K., Kelishadi, R., Sharief, W. M., Szuba, A., Khatib, R., Rahman, O., Iqbal, R., Bo, H., Yibing, Z., Wei, L. and Yusuf, S.; Prospective Urban Rural Epidemiology (PURE) Study Investigators (2020) Association of symptoms of depression with cardiovascular disease and mortality in low-, middle-, and high-income countries. JAMA Psychiatry 77, 1052-1063. https://doi.org/10.1001/jamapsychiatry.2020.1351
  83. Ren, Y., Wang, J. L., Zhang, X., Wang, H., Ye, Y., Song, L., Wang, Y. J., Tu, M. J., Wang, W. W., Yang, L. and 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
  84. Ren, Z., Yan, P., Zhu, L., Yang, H., Zhao, Y., Kirby, B. P., Waddington, J. L. and Zhen, X. (2018) Dihydromyricetin exerts a rapid antidepressant-like effect in association with enhancement of BDNF expression and inhibition of neuroinflammation. Psychopharmacology (Berl.) 235, 233-244. https://doi.org/10.1007/s00213-017-4761-z
  85. Sanmukhani, J., Satodia, V., Trivedi, J., Patel, T., Tiwari, D., Panchal, B., Goel, A. and Tripathi, C. B. (2014) Efficacy and safety of curcumin in major depressive disorder: a randomized controlled trial. Phytother. Res. 28, 579-585. https://doi.org/10.1002/ptr.5025
  86. Sarmiere, P. D. and Bamburg, J. R. (2002) Head, neck, and spines: a role for LIMK-1 in the hippocampus. Neuron 35, 3-5. https://doi.org/10.1016/S0896-6273(02)00759-6
  87. Schoenfeld, T. J., McCausland, H. C., Morris, H. D., Padmanaban, V. and Cameron, H. A. (2017) Stress and loss of adult neurogenesis differentially reduce hippocampal volume. Biol. Psychiatry 82, 914-923. https://doi.org/10.1016/j.biopsych.2017.05.013
  88. Schratt, G. M., Tuebing, F., Nigh, E. A., Kane, C. G., Sabatini, M. E., Kiebler, M. and Greenberg, M. E. (2006) A brain-specific microRNA regulates dendritic spine development. Nature 439, 283-289. https://doi.org/10.1038/nature04367
  89. Shen, J., Xu, L., Qu, C., Sun, H. and Zhang, J. (2018) Resveratrol prevents cognitive deficits induced by chronic unpredictable mild stress: Sirt1/miR-134 signalling pathway regulates CREB/BDNF expression in hippocampus in vivo and in vitro. Behav. Brain Res. 349, 1-7. https://doi.org/10.1016/j.bbr.2018.04.050
  90. Song, X., Zhou, B., Zhang, P., Lei, D., Wang, Y., Yao, G., Hayashi, T., Xia, M., Tashiro, S., Onodera, S. and Ikejima, T. (2016) Protective effect of silibinin on learning and memory impairment in LPStreated rats via ROS-BDNF-TrkB pathway. Neurochem. Res. 41, 1662-1672. https://doi.org/10.1007/s11064-016-1881-5
  91. Szewczyk, B., Pochwat, B., Muszynska, B., Opoka, W., Krakowska, A., Rafalo-Ulinska, A., Friedland, K. and Nowak, G. (2019) Antidepressant-like activity of hyperforin and changes in BDNF and zinc levels in mice exposed to chronic unpredictable mild stress. Behav. Brain Res. 372, 112045.
  92. Takei, N., Inamura, N., Kawamura, M., Namba, H., Hara, K., Yonezawa, K. and Nawa, H. (2004) Brain-derived neurotrophic factor induces mammalian target of rapamycin-dependent local activation of translation machinery and protein synthesis in neuronal dendrites. J. Neurosci. 24, 9760-9769. https://doi.org/10.1523/JNEUROSCI.1427-04.2004
  93. Taliaz, D., Stall, N., Dar, D. E. and Zangen, A. (2010) Knockdown of brain-derived neurotrophic factor in specific brain sites precipitates behaviors associated with depression and reduces neurogenesis. Mol. Psychiatry 15, 80-92. https://doi.org/10.1038/mp.2009.67
  94. Tanaka, J., Horiike, Y., Matsuzaki, M., Miyazaki, T., Ellis-Davies, G. C. and Kasai, H. (2008) Protein synthesis and neurotrophin-dependent structural plasticity of single dendritic spines. Science 319, 1683-1687. https://doi.org/10.1126/science.1152864
  95. Tayyab, M., Farheen, S., M, M. M. P., Khanam, N., Mobarak Hossain, M. and Shahi, M. H. (2019) Antidepressant and neuroprotective effects of naringenin via sonic hedgehog-GLI1 cell signaling pathway in a rat model of chronic unpredictable mild stress. Neuromolecular Med. 21, 250-261. https://doi.org/10.1007/s12017-019-08538-6
  96. Thome, J., Pesold, B., Baader, M., Hu, M., Gewirtz, J. C., Duman, R. S. and Henn, F. A. (2001) Stress differentially regulates synaptophysin and synaptotagmin expression in hippocampus. Biol. Psychiatry 50, 809-812. https://doi.org/10.1016/S0006-3223(01)01229-X
  97. Tripp, A., Oh, H., Guilloux, J. P., Martinowich, K., Lewis, D. A. and Sibille, E. (2012) Brain-derived neurotrophic factor signaling and subgenual anterior cingulate cortex dysfunction in major depressive disorder. Am. J. Psychiatry 169, 1194-1202. https://doi.org/10.1176/appi.ajp.2012.12020248
  98. Trivedi, M. H., Rush, A. J., Wisniewski, S. R., Nierenberg, A. A., Warden, D., Ritz, L., Norquist, G., Howland, R. H., Lebowitz, B., McGrath, P. J., Shores-Wilson, K., Biggs, M. M., Balasubramani, G. K. and Fava, M.; STAR*D Study Team (2006) Evaluation of outcomes with citalopram for depression using measurement-based care in STAR*D:STAR*D: implications for clinical practice. Am. J. Psychiatry 163, 28-40. https://doi.org/10.1176/appi.ajp.163.1.28
  99. Wang, C., Gan, D., Wu, J., Liao, M., Liao, X. and Ai, W. (2018a) Honokiol exerts antidepressant effects in rats exposed to chronic unpredictable mild stress by regulating brain derived neurotrophic factor level and hypothalamus-pituitary-adrenal axis activity. Neurochem. Res. 43, 1519-1528. https://doi.org/10.1007/s11064-018-2566-z
  100. Wang, J., Hodes, G. E., Zhang, H., Zhang, S., Zhao, W., Golden, S. A., Bi, W., Menard, C., Kana, V., Leboeuf, M., Xie, M., Bregman, D., Pfau, M. L., Flanigan, M. E., Esteban-Fernandez, A., Yemul, S., Sharma, A., Ho, L., Dixon, R., Merad, M., Han, M. H., Russo, S. J. and Pasinetti, G. M. (2018b) Epigenetic modulation of inflammation and synaptic plasticity promotes resilience against stress in mice. Nat. Commun. 9, 477.
  101. Wang, Y., Wang, B., Lu, J., Shi, H., Gong, S., Wang, Y., Hamdy, R. C., Chua, B. H. L., Yang, L. and Xu, X. (2017) Fisetin provides antidepressant effects by activating the tropomyosin receptor kinase B signal pathway in mice. J. Neurochem. 143, 561-568. https://doi.org/10.1111/jnc.14226
  102. Weng, L., Guo, X., Li, Y., Yang, X. and Han, Y. (2016) Apigenin reverses depression-like behavior induced by chronic corticosterone treatment in mice. Eur. J. Pharmacol. 774, 50-54. Xian, Y. F., Ip, S. P., Li, H. Q., Qu, C., Su, Z. R., Chen, J. N. and Lin, https://doi.org/10.1016/j.ejphar.2016.01.015
  103. Z. X. (2019) Isorhynchophylline exerts antidepressant-like effects in mice via modulating neuroinflammation and neurotrophins: involvement of the PI3K/Akt/GSK-3beta signaling pathway. FASEB J. 33, 10393-10408. https://doi.org/10.1096/fj.201802743RR
  104. Xiao, H., Wignall, N. and Brown, E. S. (2016) An open-label pilot study of icariin for co-morbid bipolar and alcohol use disorder. Am. J. Drug Alcohol Abuse 42, 162-167. https://doi.org/10.3109/00952990.2015.1114118
  105. Xiong, Z., Jiang, B., Wu, P. F., Tian, J., Shi, L. L., Gu, J., Hu, Z. L., Fu, H., Wang, F. and Chen, J. G. (2011) Antidepressant effects of a plant-derived flavonoid baicalein involving extracellular signalregulated kinases cascade. Biol. Pharm. Bull. 34, 253-259. https://doi.org/10.1248/bpb.34.253
  106. Xu, D., Wang, C., Zhao, W., Gao, S. and Cui, Z. (2017) Antidepressant-like effects of ginsenoside Rg5 in mice: involving of hippocampus BDNF signaling pathway. Neurosci. Lett. 645, 97-105. https://doi.org/10.1016/j.neulet.2017.02.071
  107. Xu, M., Xiao, F., Wang, M., Yan, T., Yang, H., Wu, B., Bi, K. and Jia, Y. (2019) Schisantherin B improves the pathological manifestations of mice caused by behavior desperation in different ages-depression with cognitive impairment. Biomol. Ther. (Seoul) 27, 160-167. https://doi.org/10.4062/biomolther.2018.074
  108. Xu, Y., Ku, B., Cui, L., Li, X., Barish, P. A., Foster, T. C. and Ogle, W. O. (2007) Curcumin reverses impaired hippocampal neurogenesis and increases serotonin receptor 1A mRNA and brain-derived neurotrophic factor expression in chronically stressed rats. Brain Res. 1162, 9-18. https://doi.org/10.1016/j.brainres.2007.05.071
  109. Yi, L. T., Li, J., Liu, B. B., Luo, L., Liu, Q. and Geng, D. (2014a) BDNF-ERK-CREB signalling mediates the role of miR-132 in the regulation of the effects of oleanolic acid in male mice. J. Psychiatry Neurosci. 39, 348-359. https://doi.org/10.1503/jpn.130169
  110. Yi, L. T., Liu, B. B., Li, J., Luo, L., Liu, Q., Geng, D., Tang, Y., Xia, Y. and Wu, D. (2014b) BDNF signaling is necessary for the antidepressant-like effect of naringenin. Prog. Neuropsychopharmacol. Biol. Psychiatry 48, 135-141. https://doi.org/10.1016/j.pnpbp.2013.10.002
  111. Yoshino, Y., Roy, B. and Dwivedi, Y. (2021) Differential and unique patterns of synaptic miRNA expression in dorsolateral prefrontal cortex of depressed subjects. Neuropsychopharmacology 46, 900-910. https://doi.org/10.1038/s41386-020-00861-y
  112. You, Z., Yao, Q., Shen, J., Gu, Z., Xu, H., Wu, Z., Chen, C. and Li, L. (2017) Antidepressant-like effects of ginsenoside Rg3 in mice via activation of the hippocampal BDNF signaling cascade. J. Nat. Med. 71, 367-379. https://doi.org/10.1007/s11418-016-1066-1
  113. Yu, H., Fan, C., Yang, L., Yu, S., Song, Q., Wang, P. and Mao, X. (2018) Ginsenoside Rg1 prevents chronic stress-induced depression-like behaviors and neuronal structural plasticity in rats. Cell. Physiol. Biochem. 48, 2470-2482. https://doi.org/10.1159/000492684
  114. Yu, H., Wang, D. D., Wang, Y., Liu, T., Lee, F. S. and Chen, Z. Y. (2012) Variant brain-derived neurotrophic factor Val66Met polymorphism alters vulnerability to stress and response to antidepressants. J. Neurosci. 32, 4092-4101. https://doi.org/10.1523/JNEUROSCI.5048-11.2012
  115. Yu, J. J., Pei, L. B., Zhang, Y., Wen, Z. Y. and Yang, J. L. (2015) Chronic supplementation of curcumin enhances the efficacy of antidepressants in major depressive disorder: a randomized, doubleblind, placebo-controlled pilot study. J. Clin. Psychopharmacol. 35, 406-410. https://doi.org/10.1097/jcp.0000000000000352
  116. Zanos, P. and Gould, T. D. (2018) Mechanisms of ketamine action as an antidepressant. Mol. Psychiatry 23, 801-811. https://doi.org/10.1038/mp.2017.255
  117. Zhang, J. C., Yao, W., Dong, C., Yang, C., Ren, Q., Ma, M., Han, M., Wu, J., Ushida, Y., Suganuma, H. and Hashimoto, K. (2017) Prophylactic effects of sulforaphane on depression-like behavior and dendritic changes in mice after inflammation. J. Nutr. Biochem. 39, 134-144. https://doi.org/10.1016/j.jnutbio.2016.10.004
  118. Zhao, J., Luo, D., Liang, Z., Lao, L. and Rong, J. (2017) Plant natural product puerarin ameliorates depressive behaviors and chronic pain in mice with Spared Nerve Injury (SNI). Mol. Neurobiol. 54, 2801-2812. https://doi.org/10.1007/s12035-016-9870-x
  119. Zhu, J. X., Shan, J. L., Hu, W. Q., Zeng, J. X. and Shu, J. C. (2019) Gallic acid activates hippocampal BDNF-Akt-mTOR signaling in chronic mild stress. Metab. Brain Dis. 34, 93-101. https://doi.org/10.1007/s11011-018-0328-x
  120. Zhu, X., Gao, R., Liu, Z., Cheng, Z., Qi, Y., Fan, C. and Yu, S. Y. (2016) Ginsenoside Rg1 reverses stress-induced depression-like behaviours and brain-derived neurotrophic factor expression within the prefrontal cortex. Eur. J. Neurosci. 44, 1878-1885.  https://doi.org/10.1111/ejn.13255