Intracellular inflammatory and antioxidant pathways in postmortem frontal cortex of subjects with major depression: effect of antidepressants
dc.contributor.author | Martín-Hernández, David | |
dc.contributor.author | Caso, Javier R. | |
dc.contributor.author | Meana Martínez, José Javier | |
dc.contributor.author | Callado Hernando, Luis Felipe | |
dc.contributor.author | Madrigal, José L. M. | |
dc.contributor.author | García-Bueno, Borja | |
dc.contributor.author | Leza, Juan Carlos | |
dc.date.accessioned | 2019-04-01T13:12:13Z | |
dc.date.available | 2019-04-01T13:12:13Z | |
dc.date.issued | 2018-09-04 | |
dc.identifier.citation | Journal of Neuroinflammation 15 : (2018) //Article ID 251 | es_ES |
dc.identifier.issn | 1742-2094 | |
dc.identifier.uri | http://hdl.handle.net/10810/32295 | |
dc.description.abstract | Background: Studies show that Toll-like receptors (TLRs), members of the innate immune system, might participate in the pathogenesis of the major depressive disorder (MDD). However, evidence of this participation in the brain of patients with MDD has been elusive. Methods: This work explores whether the protein expression by immunodetection assays (Western blot) of elements of TLR-4 pathways controlling inflammation and the oxidative/nitrosative stress are altered in postmortem dorsolateral prefrontal cortex of subjects with MDD. The potential modulation induced by the antidepressant treatment on these parameters was also assessed. Thirty MDD subjects (15 antidepressant-free and 15 under antidepressant treatment) were matched for gender and age to 30 controls in a paired design. Results: No significant changes in TLR-4 expression were detected. An increased expression of the TLR-4 endogenous ligand Hsp70 (+ 33%), but not of Hsp60, and the activated forms of mitogen-activated protein kinases (MAPKs) p38 (+ 47%) and JNK (+ 56%) was observed in MDD. Concomitantly, MDD subjects present a 45% decreased expression of DUSP2 (a regulator of MAPKs) and reduced (- 21%) expression of the antioxidant nuclear factor Nrf2. Antidepressant treatment did not modify the changes detected in the group with MDD and actually increased (+ 25%) the expression of p11, a protein linked with the transport of neurotransmitters and depression. Conclusion: Data indicate an altered TLR-4 immune response in the brain of subjects with MDD. Additional research focused on the mechanisms contributing to the antidepressant-induced TLR-4 pathway modulation is warranted and could help to develop new treatment strategies for MDD. | es_ES |
dc.description.sponsorship | This work was supported by the Instituto de Salud Carlos III and Spanish Ministry of Economy, Industry and Competitiveness (MINECO) through the Plan Estatal de I+D+i 2013-2016 (FIS-PI13/01102 and SAF2016-75500-R to JCL), the Agencia Estatal de Investigacion (AEI) and Fondo Europeo de Desarrollo Regional (FEDER) (SAF2017-83053-R to JRC), the Basque Government (IT-616-13), CIBERSAM and the EDR Funds. JRC and BGB are Ramon y Cajal fellows (MINECO). | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | Biomed Central | es_ES |
dc.relation | info:eu-repo/grantAgreement/MINECO/FIS-PI13/01102 | es_ES |
dc.relation | info:eu-repo/grantAgreement/MINECO/SAF2016-75500-R | es_ES |
dc.rights | info:eu-repo/semantics/openAccess | es_ES |
dc.rights.uri | http://creativecommons.org/licenses/by/3.0/es/ | * |
dc.subject | major depression | es_ES |
dc.subject | postmortem frontal cortex | es_ES |
dc.subject | antidepressants | es_ES |
dc.subject | neuroinflammation | es_ES |
dc.subject | toll-like receptor 4 pathway | es_ES |
dc.subject | mitogen-activated protein kinases | es_ES |
dc.subject | Nrf2 pathway | es_ES |
dc.subject | toll-like receptors | es_ES |
dc.subject | cingulate white-matter | es_ES |
dc.subject | necrosis-factor-alpha | es_ES |
dc.subject | p38 map kinase | es_ES |
dc.subject | signaling pathway | es_ES |
dc.subject | gene-expression | es_ES |
dc.subject | differential regulation | es_ES |
dc.subject | prefrontal cortex | es_ES |
dc.subject | activation | es_ES |
dc.subject | suicide | es_ES |
dc.title | Intracellular inflammatory and antioxidant pathways in postmortem frontal cortex of subjects with major depression: effect of antidepressants | es_ES |
dc.type | info:eu-repo/semantics/article | es_ES |
dc.rights.holder | This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. | es_ES |
dc.rights.holder | Atribución 3.0 España | * |
dc.relation.publisherversion | https://jneuroinflammation.biomedcentral.com/articles/10.1186/s12974-018-1294-2 | es_ES |
dc.identifier.doi | 10.1186/s12974-018-1294-2 | |
dc.departamentoes | Farmacología | es_ES |
dc.departamentoeu | Farmakologia | es_ES |
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