Regulation of Cortico-Thalamic JNK1/2 and ERK1/2 MAPKs and Apoptosis-Related Signaling Pathways in PDYN Gene-Deficient Mice Following Acute and Chronic Mild Stress
dc.contributor.author | Yáñez Gómez, Fernando | |
dc.contributor.author | Ramos Miguel, Alfredo | |
dc.contributor.author | García Sevilla, Jesús A. | |
dc.contributor.author | Manzanares, Jorge | |
dc.contributor.author | Femenía, Teresa | |
dc.date.accessioned | 2023-02-13T17:21:44Z | |
dc.date.available | 2023-02-13T17:21:44Z | |
dc.date.issued | 2023-01-24 | |
dc.identifier.citation | International Journal of Molecular Sciences 24(3) : (2023) // Article ID 2303 | es_ES |
dc.identifier.issn | 1422-0067 | |
dc.identifier.uri | http://hdl.handle.net/10810/59788 | |
dc.description.abstract | The crosstalk between the opioidergic system and mitogen-activated protein kinases (MAPKs) has a critical role in mediating stress-induced behaviors related to the pathophysiology of anxiety. The present study evaluated the basal status and stress-induced alterations of cortico-thalamic MAPKs and other cell fate-related signaling pathways potentially underlying the anxiogenic endophenotype of PDYN gene-deficient mice. Compared to littermates, PDYN knockout (KO) mice had lower cortical and or thalamic amounts of the phospho-activated MAPKs c-Jun N-terminal kinase (JNK1/2) and extracellular signal-regulated kinase (ERK1/2). Similarly, PDYN-KO animals displayed reduced cortico-thalamic densities of total and phosphorylated (at Ser191) species of the cell fate regulator Fas-associated protein with death domain (FADD) without alterations in the Fas receptor. Exposure to acute restraint and chronic mild stress stimuli induced the robust stimulation of JNK1/2 and ERK1/2 MAPKs, FADD, and Akt-mTOR pathways, without apparent increases in apoptotic rates. Interestingly, PDYN deficiency prevented stress-induced JNK1/2 and FADD but not ERK1/2 or Akt-mTOR hyperactivations. These findings suggest that cortico-thalamic MAPK- and FADD-dependent neuroplasticity might be altered in PDYN-KO mice. In addition, the results also indicate that the PDYN gene (and hence dynorphin release) may be required to stimulate JNK1/2 and FADD (but not ERK1/2 or Akt/mTOR) pathways under environmental stress conditions. | es_ES |
dc.description.sponsorship | This joint research was funded by Red Temática de Investigación Cooperativa en Salud–Red de Trastornos Adictivos (RETICS–RTA, Instituto de Salud Carlos III [ISCIII], MCIU/AEI/FEDER), Grupos RD06/0001/0004 (J.M.) and RD06/0001/0003 (J.A.G.-S.). J.M. also received financial support from Proyectos de Investigación en Salud—ISCIII (grant RD. PI18/00576), Red de Investigación en Atención Primaria de Adicciones (grant RD21/0009/0008), and Delegación del Gobierno para el Plan Nacional Sobre Drogas (PNSD, grant 2019I012) from the Spanish Ministry of Health (MSC). This study was also supported by MCIU/AEI/FEDER (grants RTI2018-094414-A-I00 to A.R.-M., PID2019-109323RA-I00 to T.F., and SAF2008-01311 to J.A.G.-S.), and MSC/FEDER (FIS 05/0429 to J.M). A.R.-M. (grant RYC-2016-19282) and T.F. (grant RYC-2017-22666) are ‘Ramón y Cajal’ Researchers. | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | MDPI | es_ES |
dc.relation | info:eu-repo/grantAgreement/MICIU/RTI2018-094414-A-I00 | es_ES |
dc.relation | info:eu-repo/grantAgreement/MICINN/PID2019-109323RA-I00 | es_ES |
dc.relation | info:eu-repo/grantAgreement/MICINN/SAF2008-01311 | es_ES |
dc.relation | info:eu-repo/grantAgreement/MINECO/RYC-2016-19282 | es_ES |
dc.relation | info:eu-repo/grantAgreement/MINECO/RYC-2017-22666 | es_ES |
dc.rights | info:eu-repo/semantics/openAccess | es_ES |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | |
dc.subject | prodynorphin | es_ES |
dc.subject | JNK | es_ES |
dc.subject | ERK | es_ES |
dc.subject | chronic mild stress | es_ES |
dc.subject | apoptosis | es_ES |
dc.subject | phosphorylation | es_ES |
dc.title | Regulation of Cortico-Thalamic JNK1/2 and ERK1/2 MAPKs and Apoptosis-Related Signaling Pathways in PDYN Gene-Deficient Mice Following Acute and Chronic Mild Stress | es_ES |
dc.type | info:eu-repo/semantics/article | es_ES |
dc.date.updated | 2023-02-10T14:28:52Z | |
dc.rights.holder | © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/ 4.0/). | es_ES |
dc.relation.publisherversion | https://www.mdpi.com/1422-0067/24/3/2303 | es_ES |
dc.identifier.doi | 10.3390/ijms24032303 | |
dc.departamentoes | Farmacología | |
dc.departamentoeu | Farmakologia |
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Except where otherwise noted, this item's license is described as © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/ 4.0/).