ER stress in mouse serotonin neurons triggers a depressive phenotype alleviated by ketamine targeting eIF2α signaling.
iScience May 17, 2024 Lluis Miquel-Rio, Unai Sarriés-Serrano, María Sancho-Alonso et al. 16 citations
Depression involves disruptions in the endoplasmic reticulum (ER) of serotonin neurons. In mice, artificially inducing ER stress in these neurons reduced Egr1-dependent serotonin activity and neurotransmission, leading to impaired neuroplasticity in forebrain regions and depressive-like behaviors. Ketamine reversed these effects by activating eIF2α signaling, which rapidly restored neuroplasticity. The findings identify ER stress in serotonin neurons as a cellular mechanism in depression and highlight eIF2α as a key target for ketamine's fast antidepressant action.