The beneficial effects of vortioxetine on BDNF, CREB, S100B, β amyloid, and glutamate NR2b receptors in chronic unpredictable mild stress model of depression

• Published in: Psychopharmacology Vol. 240; no. 12; pp. 2499 - 2513
• Main Authors: Ünal, Gülin Özdamar, Erkılınç, Gamze, Öztürk, Kuyaş Hekimler, Doguç, Duygu Kumbul, Özmen, Özlem
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.12.2023; Springer Nature B.V
• Subjects: Amyloid; Amyloid beta-Peptides - metabolism; Animal models; Animals; Biomedical and Life Sciences; Biomedicine; Brain injury; Brain-derived neurotrophic factor; Brain-Derived Neurotrophic Factor - metabolism; Cyclic AMP response element-binding protein; Depression - drug therapy; Depression - metabolism; Disease Models, Animal; Enzyme-linked immunosorbent assay; Fluoxetine; Glutamates - metabolism; Hippocampus; Humans; Influenza; Mental depression; Mental disorders; Neurodegeneration; Neurosciences; Original Investigation; Pharmacology/Toxicology; Psychiatry; Rats; Rats, Wistar; S100 Calcium Binding Protein beta Subunit - metabolism; S100 Calcium Binding Protein beta Subunit - pharmacology; S100b protein; Stress, Psychological - complications; Stress, Psychological - drug therapy; Stress, Psychological - metabolism; Sucrose; Sucrose - pharmacology; Vortioxetine - pharmacology; β-Amyloid; NR2b; Aβ; CREB; BDNF; S100; Chronic unpredictable stress model; Vortioxetine
• ISSN: 0033-3158; 1432-2072
• DOI: 10.1007/s00213-023-06445-0

Background Depression, one of the most significant mental disorders, is still poorly understood in terms of its pathogenetic mechanisms despite its well-recognized association with stress. Objectives The current study’s goal was to ascertain how the novel antidepressant drug vortioxetine (VOR) affected the BDNF (brain-derived neurotrophic factor), S100, amyloid β (Aβ), CREB (cAMP response element-binding protein), and NR2B, as well as its impact on depression-like behaviors, and tissue damage in an experimental rodent model of depression caused by chronic unpredictable stress. Methods We employed twenty-eight Wistar albino male rats, and we randomly divided them into four groups, each consisting of 7 rats: control, CUMS (chronic unpredictable mild stress), CUMS+vortioxetine (CUMS+VOR), and CUMS+fluoxetine (CUMS+FLU). Sucrose preference and forced swimming tests (SPT and FST, respectively), PCR, ELISA, and histopathological and immunohistochemical evaluation were made on brains. Results The behaviors of reduced immobility in the FST and increased sucrose preference were observed in the CUMS group and they improved in the groups treated with VOR and FLU. Compared with the control group, the group exposed to CUMS showed increased Aβ and decreased BDNF, CREB, and S-100 expressions, as well as neuronal degeneration ( p <0.001). VOR and FLU treatment ameliorate the findings. Conclusions This study demonstrated significant ameliorative effects of VOR in an experimental model of chronic unpredictable depression to reduce brain tissue damage and depression-like behaviors in rats. Graphical abstract Effects of CUMS on the brain and possible effects of VOR