Brain-derived neurotrophic factor modulation in response to oxidative stress and corticosterone: role of scopolamine and mirtazapine

Major Depressive Disorder (MDD) is a very complex disease, challenging to study and manage. The complexities of MDD require extensive research of its mechanisms to develop more effective therapeutic approaches. Crucial in the context of this disease is the role of brain-derived neurotrophic factor (BDNF) signaling pathway. This manuscript aims to explore the complex relationship between MDD and BDNF signaling pathway, focusing on how BDNF is modulated in response to oxidative stress and corticosterone, known to be altered in MDD and contributing to the pathology of the disorder, when treated with scopolamine and mirtazapine. To assess BDNF levels after the different treatment conditions, rat hippocampal slices and mice primary hippocampus and cortical cell culture were analyzed by immunofluorescence and Western blot. Both mirtazapine and scopolamine under stress conditions induced by hydrogen peroxide (H2O2) and corticosterone, had a significant impact on BDNF levels, and this was distinct in different neuronal models. Mirtazapine, especially when combined with H2O2, altered BDNF expression. Scopolamine when combined with both stressors also altered BDNF levels. However, its effects varied depending on the specific neuronal model and stress condition. In accordance with BDNF results, phosphorylated tropomyosin receptor kinase B (pTrkB) presented increased activation when neuronal cells subjected to stress were treated with mirtazapine or scopolamine. Collectively, this study highlights the complex connection between these compounds, stress conditions, and BDNF/TrkB modulation, supporting the potential therapeutic effects of scopolamine and mirtazapine in modulating BDNF levels, even in stressful conditions.