ArticleiScience2024
ER stress in mouse serotonin neurons triggers a depressive phenotype alleviated by ketamine targeting eIF2α signaling.
Article in iScience, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed.
- MANF in the lateral septum dynamically regulates endoplasmic reticulum function in chronic stress response.Translational psychiatry · 2026Article
- Role of α-Synuclein in the Prefrontal Cortex: From Physiological Synaptic Modulation to Synaptic Failure in Parkinson's Disease.Biomedicines · 2026Review
- Effects of psychosocial stress on myocardial injury by modulating endoplasmic reticulum stress-induced autophagy and inflammation.iScience · 2025Article
- A molecular convergence in the triad of parkinson's disease, depressive disorder and gut health is revealed by the inflammation-miRNA axis.Journal of neuroinflammation · 2025Article
- Early synaptic changes and reduced brain connectivity in PD-like mice with depressive phenotype.NPJ Parkinson's disease · 2025Article
- Precision Recovery After Spinal Cord Injury: Integrating CRISPR Technologies, AI-Driven Therapeutics, Single-Cell Omics, and System Neuroregeneration.International journal of molecular sciences · 2025Review
- Defective regulation of the eIF2-eIF2B translational axis underlies depressive-like behavior in mice and correlates with major depressive disorder in humans.Translational psychiatry · 2024Article
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Authors and funding
10 authors.
Funding
No grant is acknowledged in the PubMed record.
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.
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