Yáñez-Gómez, FernandoRamos-Miguel, AlfredoGarcía-Sevilla, Jesús AManzanares, JorgeFemenía, Teresa2024-10-092024-10-092023-01-24Yáñez-Gómez F, Ramos-Miguel A, García-Sevilla JA, Manzanares J, Femenía T. 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. Int J Mol Sci. 2023 Jan 24;24(3):2303.https://hdl.handle.net/20.500.13003/18868https://hdl.handle.net/20.500.12105/23763The 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.enghttp://creativecommons.org/licenses/by/4.0/Mitogen-Activated Protein Kinase KinasesExtracellular Signal-Regulated MAP KinasesApoptosisPhosphorylationProto-Oncogene Proteins c-aktAnimalsSignal TransductionJNK Mitogen-Activated Protein KinasesTOR Serine-Threonine Kinasesp38 Mitogen-Activated Protein KinasesMiceresearch articleAtribución 4.0 Internacional3676862624310.3390/ijms240323031422-0067International journal of molecular sciencesopen accessTransducción de SeñalProteínas Quinasas JNK Activadas por MitógenosAnimalesFosforilaciónSerina-Treonina Quinasas TORProteínas Quinasas p38 Activadas por MitógenosQuinasas MAP Reguladas por Señal ExtracelularQuinasas de Proteína Quinasa Activadas por MitógenosApoptosisRatonesProteínas Proto-Oncogénicas c-akt932797700001