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
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 ot...
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MDPI AG
2023-01-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/3/2303 |
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| author | Fernando Yáñez-Gómez Alfredo Ramos-Miguel Jesús A. García-Sevilla Jorge Manzanares Teresa Femenía |
| author_facet | Fernando Yáñez-Gómez Alfredo Ramos-Miguel Jesús A. García-Sevilla Jorge Manzanares Teresa Femenía |
| author_sort | Fernando Yáñez-Gómez |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-11T09:42:00Z |
| format | Article |
| id | doaj.art-94b58504fc934ab298b046e5892cc72b |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T09:42:00Z |
| publishDate | 2023-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-94b58504fc934ab298b046e5892cc72b2023-11-16T16:55:19ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-01-01243230310.3390/ijms24032303Regulation of Cortico-Thalamic JNK1/2 and ERK1/2 MAPKs and Apoptosis-Related Signaling Pathways in PDYN Gene-Deficient Mice Following Acute and Chronic Mild StressFernando Yáñez-Gómez0Alfredo Ramos-Miguel1Jesús A. García-Sevilla2Jorge Manzanares3Teresa Femenía4Laboratorio de Neurofarmacología, IUNICS, Universitat de les Illes Balears, Crta. Valldemossa km 7.5, 07122 Palma de Mallorca, SpainDepartment of Pharmacology, University of the Basque Country (UPV/EHU), Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Barrio Sarriena S/N, 48940 Leioa, SpainLaboratorio de Neurofarmacología, IUNICS, Universitat de les Illes Balears, Crta. Valldemossa km 7.5, 07122 Palma de Mallorca, SpainInstituto de Neurociencias de Alicante, Universidad Miguel Hernández-CSIC, Avda. de Ramón y Cajal s/n, San Juan de Alicante, 03550 Alicante, SpainInstituto de Neurociencias de Alicante, Universidad Miguel Hernández-CSIC, Avda. de Ramón y Cajal s/n, San Juan de Alicante, 03550 Alicante, SpainThe 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.https://www.mdpi.com/1422-0067/24/3/2303prodynorphinJNKERKchronic mild stressapoptosisphosphorylation |
| spellingShingle | Fernando Yáñez-Gómez Alfredo Ramos-Miguel Jesús A. García-Sevilla Jorge Manzanares Teresa Femenía 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 International Journal of Molecular Sciences prodynorphin JNK ERK chronic mild stress apoptosis phosphorylation |
| 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| topic | prodynorphin JNK ERK chronic mild stress apoptosis phosphorylation |
| url | https://www.mdpi.com/1422-0067/24/3/2303 |
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