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The Dysfunction of Carcinogenesis- and Apoptosis-Associated Genes that Develops in the Hypothalamus under Chronic Social Defeat Stress in Male Mice

Anna G. Galyamina1#, Dmitry A. Smagin1#, Irina L. Kovalenko1, Olga E. Redina1, Vladimir N. Babenko1, and Natalia N. Kudryavtseva1,2,a*

1FRC Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences, 630090 Novosibirsk, Russia

2Pavlov Institute of Physiology, Russian Academy of Sciences, 199034 Saint Petersburg, Russia

* To whom correspondence should be addressed.

# These authors contributed equally to this study.

Received August 15, 2022; Revised August 25, 2022; Accepted August 25, 2022
Chronic social stress caused by daily agonistic interactions in male mice leads to a mixed anxiety/depression-like disorder that is accompanied by the development of psychogenic immunodeficiency and stimulation of oncogenic processes concurrently with many neurotranscriptomic changes in brain regions. The aim of the study was to identify carcinogenesis- and apoptosis-associated differentially expressed genes (DEGs) in the hypothalamus of male mice with depression-like symptoms and, for comparison, in aggressive male mice with positive social experience. To obtain two groups of animals with the opposite 20-day social experiences, a model of chronic social conflict was used. Analysis of RNA-Seq data revealed similar expression changes for many DEGs between the aggressive and depressed animals in comparison with the control group; however, the number of DEGs was significantly lower in the aggressive than in the depressed mice. It is likely that the observed unidirectional changes in the expression of carcinogenesis- and apoptosis-associated genes in the two experimental groups may be a result of prolonged social stress (of different severity) caused by the agonistic interactions. In addition, 26 DEGs were found that did not change expression in the aggressive animals and could be considered genes promoting carcinogenesis or inhibiting apoptosis. Akt1, Bag6, Foxp4, Mapk3, Mapk8, Nol3, Pdcd10, and Xiap were identified as genes whose expression most strongly correlated with the expression of other DEGs, suggesting that their protein products play a role in coordination of the neurotranscriptomic changes in the hypothalamus. Further research into functions of these genes may be useful for the development of pharmacotherapies for psychosomatic pathologies.
KEY WORDS: apoptosis, carcinogenesis, differentially expressed gene, hypothalamus, RNA sequencing, chronic social defeat stress

DOI: 10.1134/S0006297922090152