Researchers have identified a group of ribosomal protein genes that connect animal models of depression to human patients with major depressive disorder (MDD). While studying depression treatments, scientists often use mouse models subjected to various stressors to induce a state similar to depression. In this study, published in PNAS Nexus, the researchers sought to determine if this state was molecularly similar to human MDD by examining transcriptomics data from postmortem human brain tissue and several mouse stress models.
They discovered that ribosomal protein genes were consistently dysregulated in these stress paradigms. Stress hormones were found to potentially trigger this dysregulation, which could be reversed during the remission phase of depression or attenuated by blocking hormone receptors.
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A seeded gene co-expression analysis suggested that these ribosomal proteins played a role in the homeostatic feedback regulation of pathways related to synaptic communication. Ribosomes, cellular organelles responsible for protein synthesis and translation, are involved in the stress response in various organisms.
The findings suggest that stress-induced ribosome dysregulation contributes to human depression by altering protein synthesis and subsequently affecting neural synapse function, leading to mood disorders.