Roles of BDNF/TrkB Signaling Pathway in Anti-Depressant Effect of Vortioxetine

Author(s): Xiaoming Si, Jingyu Jin

Objective To investigate the effects of vortioxetine on BDNF/TrkB signal pathway. Methods Kunming mice were randomized into control group and chronic unpredictable mild stress (CUMS) group. After establishment of depressive models verified by sucrose preference test, the mice in CUMS group were divided into model group and vortioxetine group. The antidepressant effect of vortioxetine was analyzed by Y-maze test, forced swim test and open field test. The expressions of brain-derived neurotrophic factor (BDNF) and TrkB were evaluated with Western blotting. Results Vortioxetine significantly shortened the immobility time of the depressive mice in forced swim test without affecting the locomotor activity of the mice in open fields, suggesting the antidepressant effect of against depression in mice. Vortioxetine significantly improved the depression-like behavior. Vortioxetine significantly increased the expression of BDNF in the hippocampus of the mice (p < 0.01). Conclusion Vortioxetine improves the behaviors of mice with depression possibly by affecting the BDNF/TrkB signal pathway.

Vortioxetine, TrkB, Brain-Derived Neurotrophic Factor, Depression

1. Bromet E, Andrade LH, Hwang I, Sampson NA, Alonso J, de Girolamo G, et al. Cross-national epidemiology of DSM-IV major depressive episode. BMC Medicine. 2011;9:90.
2. CJL M, AD L. Evidence-based health policy-lessons from the global burden of disease study. Science. 1996:740-7.
3. Ferrari AJ, Charlson FJ, Norman RE, Patten SB, Freedman G, Murray CJ, et al. Burden of depressive disorders by country, sex, age, and year: findings from the global burden of disease study 2010. PLoS medicine. 2013;10:e1001547.
4. Gibb A, Deeks ED. Vortioxetine: first global approval. Drugs. 2014;74:135-45.
5. Nash J, Nutt D. Antidepressants. Psychiatry. 2007;6:289-94.
6. Li K, Shen S, Ji Y-T, Li X-Y, Zhang L-S, Wang X-D. Melatonin Augments the Effects of Fluoxetine on Depression-Like Behavior and Hippocampal BDNF–TrkB Signaling. Neuroscience Bulletin. 2017.
7. Wang J-M, Yang L-H, Zhang Y-Y, Niu C-L, Cui Y, Feng W-S, et al. BDNF and COX-2 participate in anti-depressive mechanisms of catalpol in rats undergoing chronic unpredictable mild stress. Physiology & behavior. 2015;151:360-8.
8. Lim MS, Nam SH, Kim SJ, Kang SY, Lee YS, Kang KS. Signaling pathways of the early differentiation of neural stem cells by neurotrophin-3. Biochemical and biophysical research communications. 2007;357:903-9.
9. Sagud M, Nikolac Perkovic M, Vuksan-Cusa B, Maravic A, Svob Strac D, Mihaljevic Peles A, et al. A prospective, longitudinal study of platelet serotonin and plasma brain-derived neurotrophic factor concentrations in major depression: effects of vortioxetine treatment. Psychopharmacology. 2016;233:3259-67.
10. Porsolt RD, Bertin A, Jalfre M. Behavioral despair in mice: a primary screening test for antidepressants. Archives internationales de pharmacodynamie et de therapie. 1977;229:327-36.
11. Kim KS, Kwon HJ, Baek IS, Han PL. Repeated Short-term (2hx14d) Emotional Stress Induces Lasting Depression-like Behavior in Mice. Experimental neurobiology. 2012;21:16-22.
12. Yi L-T, Liu B-B, Li J, Luo L, Liu Q, Geng D, et al. BDNF signaling is necessary for the antidepressant-like effect of naringenin. Progress in Neuro-Psychopharmacology and Biological Psychiatry. 2014;48:135-41.
13. Ayuob NN. Evaluation of the antidepressant-like effect of musk in an animal model of depression: how it works. Anatomical science international. 2017;92:539-53.
14. Mu RH, Fang XY, Wang SS, Li CF, Chen SM, Chen XM, et al. Antidepressant-like effects of standardized gypenosides: involvement of brain-derived neurotrophic factor signaling in hippocampus. Psychopharmacology. 2016;233:3211-21.