@article{10902/33034,
year = {2024},
url = {https://hdl.handle.net/10902/33034},
abstract = {Depression is a devastating mood disorder that causes significant disability worldwide. Current knowledge of its pathophysiology remains modest and clear biological markers are lacking. Emerging evidence from human and animal models reveals persistent alterations in endoplasmic reticulum (ER) homeostasis, suggesting that ER stress-related signaling pathways may be targets for prevention and treatment. However, the neurobiological basis linking the pathways involved in depression-related ER stress remains unknown. Here, we report that an induced model of ER stress in mouse serotonin (5-HT) neurons is associated with reduced Egr1-dependent 5-HT cellular activity and 5-HT neurotransmission, resulting in neuroplasticity deficits in forebrain regions and a depressive-like phenotype. Ketamine administration engages downstream eIF2α signaling to trigger rapid neuroplasticity events that rescue the depressive-like effects. Collectively, these data identify ER stress in 5-HT neurons as a cellular pathway involved in the pathophysiology of depression and show that eIF2α is critical in eliciting ketamine's fast antidepressant effects.},
organization = {ACKNOWLEDGMENTS: This work was supported by MCIU/AEI/FEDER, UE grant (PID2019-105136RB-100, MCIN/AEI/10.13039/501100011033 to AB, and SAF2015-67457-R to FPC), Fundación La Marató TV3 (202207), and AGAUR 2021-SGR-01358, Catalan Government. CB/07/09/0034 and CB/07/09/0008 Center for Networked Biomedical Research on Mental Health (CIBERSAM). We also thank the Spanish Stress Research Network, MCIN/AEI/10.13039/501100011033. USS is a recipient of a fellowship from the Non-Doctor Researcher Formation Pre-doctoral Program of Basque Government, Spain. MSA has a Margarita Salas Grant (MS21-132) from the University of Valencia (requalification of the Spanish University System of the Ministry of Universities of the Government of Spain, financed by the European Union, Next Generation EU).},
publisher = {Elsevier},
publisher = {iScience, 2024, 27, 109787},
title = {ER stress in mouse serotonin neurons triggers a depressive phenotype alleviated by ketamine targeting eIF2a signaling},
author = {Miquel-Rio, Lluis and Sarriés-Serrano, Unai and Sánchez-Alonso, María and Florensa Zanuy, Eva Adriana and Paz, Verónica and Ruiz-Bronchal, Esther and Manashirov, Sharon and Campa, Leticia and Pilar Cuéllar, María Fuencisla and Bortolozzi, Analia},
}