The Mysterious Link Between Ribosomes and Major Depressive Disorder

Relatively little is known about the potential biological mechanisms underlying the heterogeneous manifestation of Major Depressive Disorder (MDD). This emphasizes the need for a conceptual framework to explain the variability, and to bridge the gap between animal models and clinical endpoints. Recent developments in investigations have drawn attention to a potential correlation between ribosomes and human depression. A study titled, "Ribosomal dysregulation: A conserved pathophysiological mechanism in human depression and mouse chronic stress", on the international journal PNAS Nexus, has offered some insights into this connection.

Unveiling the Role of Ribosomal Dysregulation in Depression

In particular, researchers uncovered that a set of ribosomal proteins could possibly link animal models of depression to patients with MDD. To study potential therapeutics for human depression, scientists used mouse models. By exposing the mice to unpredictable, uncontrollable stressors for days or weeks, the mice were induced into a state similar to depression. However, whether this state at the molecular level is similar to what patients with severe depression experience was not known.

To find these answers, researchers, including Xiaolu Zhang, analysed transcriptomic data from post-mortem human brain tissue and various stressed mouse model organisms, aiming to uncover some conserved genes. They found that ribosomal protein genes (RPGs)were globally dysregulated in these stress paradigms. Further research suggested that this dysregulation might be induced by stress hormones, and is reversible during depression remission. When hormone receptor function was blocked, this dysregulation weakened.

Fig. 1 Ribosomal subunit proteins and depression.¹

Ribosome Proteins and Synaptic Communication

Upon performing a seed gene co-expression analysis, it was found that the ribosomal protein under scrutiny was crucial for the homeostatic feedback regulation of synaptic communication pathways. Ribosomes are organelles that translate and synthesize proteins and participate in stress responses across a range of organisms such as yeast, bacteria, and animals. In essence, these findings suggest that stress-induced ribosomal functional dysregulation might act as a complex foundation for the occurrence of human depression. Dysregulation of ribosomal function might alter the synthesis of alternate proteins, thereby changing the function of neurons synapses. Often, these changes manifest as emotional disorders in organisms.

Implications for Understanding and Treating Depression

In summary, these research findings provide a basis for the establishment of a potential something hypothesis - those changes in the expression of ribosome protein genes and the synaptic dysregulation behind the occurrences of severe depression and chronic stress-related emotional disorders caused by ribosomes. The role of ribosomal heterogeneity in the variable expression of depression and other emotional disorders was also discussed. Thus, this groundbreaking research might be the key to unlocking the complex puzzle of understanding the biological mechanisms underlying the clinical presentation of major depressive disorder. By fostering this understanding of the role of ribosomes in depression, new avenues for potential targeted therapeutic interventions can be revealed. However, most importantly, this draws attention to depression as a complex, multi-faceted disorder that is more than just feelings of sadness. It is, in fact, a physical illness tied to intricate molecular processes.

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Reference

1. Zhang, Jialing, et al. "iTRAQ-based protein profiling in CUMS rats provides insights into hippocampal ribosome lesion and ras protein changes underlying synaptic plasticity in depression." Neural Plasticity 2019 (2019).