Chronic Stress Alters Lipid Mediator Profiles Associated with Immune-Related Gene Expressions in Mouse Bone Marrow and Spleen
Despite the importance of lipid mediators in stress and depression and their link to inflammation, the influence of stress on these mediators and their role in inflammation is not fully understood. This study used RNA-seq, LC-MS/MS, and flow cytometry analyses in a mouse model subjected to chronic social defeat stress to explore the effects of acute and chronic stress on lipid mediators, gene expression, and cell population in the bone marrow and spleen. We observed that chronic stress in the bone marrow precipitated a persistent lymphoid-to-myeloid transition, accompanied by corresponding gene expression changes. This change was associated with decreased levels of 15-deoxy-d12,14-prostaglandin J2, a lipid mediator that inhibits inflammation. Conversely, in the spleen, chronic stress led to a transient lymphoid-to-myeloid transition, alongside gene expression patterns suggestive of extramedullary hematopoiesis. These changes were linked to lower levels of 12-HEPE and resolvins, both critical for inhibiting and resolving inflammation. Our findings highlight the significant role of anti-inflammatory and pro-resolving lipid mediators in the immune responses induced by chronic stress in the bone marrow and spleen. This study paves the way for understanding how these lipid mediators contribute to the immune mechanisms of stress and depression. Overall design: Two to six biological replicates were analyzed for each of 10 conditions (five stress conditions; two organs per stress condition)