Influence of Chronic Social Stress on the Expression of Genes Associated with Neurotransmitter Systems in the Hypothalamus of Male Mice

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Chronic social stress caused by repeated negative experiences in agonistic interactions induces depressive-like behavior in male mice. The aim of the study was to study changes in the expression of genes encoding proteins involved in the metabolism, reception, and transport of catecholamines, opioids, glutamate, and GABA under the influence of chronic stress. Hypothalamic samples were sequenced using RNA-Seq. It was shown that the expression of the catecholaminergic genes Adra1b, Adrbk1, Comtd1, Ppp1r1b, Sncb, Sncg, and Th in depressed animals is increased, while the expression of the Maoa and Maob genes is reduced. The expression of the opioidergic and cannabinoidergic genes Pdyn, Penk, Pomc, Pnoc, Ogfr, and Faah was upregulated, while that of the Oprk1, Opcml, Ogfrl1, and Cnr1 genes was downregulated. The expression of the glutamatergic genes Grik3, Grik4, Grik5, Grin1, Grm2, and Grm4 was increased, while the expression of the Gria3, Grik1, Grik2, Grin2a, Grin3a, Grm5, Grm8, and Gad2 genes was reduced. The expression of the GABAergic genes Gabre, Gabbr2, and Slc6a11 was higher, while the expression of the Gabra1, Gabra2, Gabra3, Gabrb2, Gabrb3, Gabrg1, Gabrg2, and Slc6a13 genes was lower in depressed animals. The data suggest that gene products that interact with other neurotransmitter systems (Th, Gad2, Gabra1, Gabrg2, Grin1, and Pdyn) may be of interest as potential targets for pharmacological correction of the consequences of social stress.

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Sobre autores

I. Kovalenko

FRC Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences

Autor responsável pela correspondência
Email: koir0909@mail.ru
Rússia, Novosibirsk, 630090

A. Galyamina

FRC Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences

Email: koir0909@mail.ru
Rússia, Novosibirsk, 630090

D. Smagin

FRC Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences

Email: koir0909@mail.ru
Rússia, Novosibirsk, 630090

N. Kudryavtseva

FRC Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences; Pavlov Institute of Physiology, Russian Academy of Sciences

Email: koir0909@mail.ru
Rússia, Novosibirsk, 630090; Saint-Petersburg, 199034

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2. Fig. 1. Expression of DEG of catecholaminergic systems in GPT in depressed male mice. White columns are control, dark columns are depressive mice. * p < 0.05, ** p < 0.01, *** p < 0.001 vs. control. An auxiliary scale is presented for the Sncb gene. The data is expressed in FPKM units. # – previously published data [21].

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3. Fig. 2. Expression of DEG opioidergic and cannabinoid systems in GPT in depressed male mice. White columns are control, dark columns are depressive mice. *p < 0.05, ** p < 0.01, *** p < 0.001 vs. control. The data is expressed in FPKM units.

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4. Fig. 3. Expression of the DEG glutamatergic system in GPT in depressed male mice. White columns are control, dark columns are depressive mice. *p < 0.05, **p < 0.01, ***p < 0.001 vs. control. An auxiliary scale is presented for the Gad2, Grik5, and Grin1 genes. The data is expressed in FPKM units.

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5. Fig. 4. Expression of the DEG GABAergic system in GPT in depressed male mice. White columns are control, dark columns are depressive mice. *p < 0.05, **p < 0.01, ***p < 0.001 vs. control. An auxiliary scale is presented for the Slc6a11 gene. The data is expressed in FPKM units.

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6. Fig. 5. Functional relationships of proteins encoded by DEG, established according to the STRING database (http://string-db.org /) in depressed animals in GPT.

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