Common Genes To Different Species Have Linkage With Depression Development

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Russian scientists performed a cross-species analysis of brain gene expression in danio fish, rats and humans to identify new common molecular targets for the therapy of affective disorders of the central nervous system induced by chronic stress. The study was able to identify several key brain proteins that may play important roles in the pathogenesis of affective disorders.

The article was published in the journal Scientific Reports. Affective disorders, also known as mood disorders, are a group of mental illnesses that involve changes in emotional states. They include various forms of depression and mania, psychosis, and increased anxiety. They are widespread because they occur not only as independent mental pathologies, but also as complications of neurological and other somatic diseases.

This fact determines the difficulty of diagnosis: people classify low mood, anxiety and irritability as temporary, situational manifestations. According to statistics, emotional disorders of varying severity occur in 20% of people, but only a quarter of them receive qualified help.

Despite the high prevalence of such disorders, many of the pathological mechanisms are still unclear. Animal models, such as rats and danio fish, are often used to study affective disorders. However, not all data obtained in animals can be extrapolated to humans. This forces scientists to look for new techniques to help identify evolutionarily stable molecular mechanisms for the development of affective disorders.

The study used both traditional methods, such as comparing “healthy” humans and animals to those with disease symptoms, and more sophisticated approaches. These methods include cross-species analysis by comparing orthologs – “similar” genes from different organisms that perform a similar function and come from the same DNA sequence.

For the analysis, they used sequencing data from RNA, a ribonucleic acid that is an intermediate biomolecule used to transfer information from the “source” DNA to proteins that perform a specific function. Whole-genome DNA sequencing provides an overall picture of the diversity of genes in the body, but it cannot answer the question of which genes are active in different cells and tissues at any given time.

For this reason, RNA sequencing is used to analyze gene expression, which makes it possible to establish a direct link between gene activity and specific physiological conditions. Scientists have been able to document some general mechanisms of response to stress, including changes in the activity of genes responsible for calcium signaling, cell adhesion molecules, and oxidative phosphorylation.

The researchers identified common genes involved in pathogenesis in all three species, providing evolutionarily stable biomarkers of affective pathology. The data were retested using several different techniques. In the long term, the results of the study may have applications in the diagnosis and treatment of affective disorders.

Scientists from the MIPT (Moscow Institute of Physics and Technology), the Almazov National Medical Research Centre, Sirius University, the Institute of Translational Biomedicine (Saint-Petersburg State University), the Granov Russian Research Center for Radiology and Surgical Technologies, the Institute of Neurology and Medicine (Novosibirsk), and the Ural Federal University participated in the work.