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

Autor:	Correia AS; OncoPharma Research Group, Center for Health Technology and Services Research (CINTESIS), Rua Doutor Plácido da Costa, 4200-450 Porto, Portugal; Instituto de Ciências Biomédicas Abel Salazar (ICBAS), University of Porto, Rua de Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal; CINTESIS@RISE, Faculty of Medicine, University of Porto, Alameda Professor Hernâni Monteiro, 4200-319 Porto, Portugal., Torrado M; Instituto de Ciências Biomédicas Abel Salazar (ICBAS), University of Porto, Rua de Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal; i3S-Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Rua Alfredo Allen 208, 4200-135 Porto, Portugal; INEB - Instituto Nacional de Engenharia Biomédica, Universidade do Porto, Rua Alfredo Allen 208, 4200-135 Porto, Portugal., Costa-Coelho T; Instituto de Farmacologia e Neurociências, Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisboa, Portugal; Instituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisboa, Portugal; Research Institute for Medicines (iMed.ULisboa), Faculdade de Farmácia, Universidade de Lisboa, 1649-003 Lisboa, Portugal., Carvalho ED; i3S-Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Rua Alfredo Allen 208, 4200-135 Porto, Portugal; INEB - Instituto Nacional de Engenharia Biomédica, Universidade do Porto, Rua Alfredo Allen 208, 4200-135 Porto, Portugal; FEUP-Faculdade de Engenharia, Universidade do Porto, 4200-465 Porto, Portugal., Inteiro-Oliveira S; Instituto de Farmacologia e Neurociências, Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisboa, Portugal; Instituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisboa, Portugal., Diógenes MJ; Instituto de Farmacologia e Neurociências, Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisboa, Portugal; Instituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisboa, Portugal., Pêgo AP; Instituto de Ciências Biomédicas Abel Salazar (ICBAS), University of Porto, Rua de Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal; i3S-Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Rua Alfredo Allen 208, 4200-135 Porto, Portugal; INEB - Instituto Nacional de Engenharia Biomédica, Universidade do Porto, Rua Alfredo Allen 208, 4200-135 Porto, Portugal., Santos SD; i3S-Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Rua Alfredo Allen 208, 4200-135 Porto, Portugal; INEB - Instituto Nacional de Engenharia Biomédica, Universidade do Porto, Rua Alfredo Allen 208, 4200-135 Porto, Portugal., Sebastião AM; Instituto de Farmacologia e Neurociências, Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisboa, Portugal; Instituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisboa, Portugal., Vale N; OncoPharma Research Group, Center for Health Technology and Services Research (CINTESIS), Rua Doutor Plácido da Costa, 4200-450 Porto, Portugal; CINTESIS@RISE, Faculty of Medicine, University of Porto, Alameda Professor Hernâni Monteiro, 4200-319 Porto, Portugal; Department of Community Medicine, Health Information and Decision (MEDCIDS), Faculty of Medicine, University of Porto, Rua Doutor Plácido da Costa, 4200-450 Porto, Portugal. Electronic address: nunovale@med.up.pt.
Jazyk:	angličtina
Zdroj:	Life sciences [Life Sci] 2024 Dec 01; Vol. 358, pp. 123133. Date of Electronic Publication: 2024 Oct 15.
DOI:	10.1016/j.lfs.2024.123133
Abstrakt:	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. Aim: 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. Methods: 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. Key Findings: Both mirtazapine and scopolamine under stress conditions induced by hydrogen peroxide (H 2 O 2 ) and corticosterone, had a significant impact on BDNF levels, and this was distinct in different neuronal models. Mirtazapine, especially when combined with H 2 O 2 , 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. Significance: 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. Competing Interests: Declaration of competing interest The authors declare that they have no conflicts of interest. (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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