Effect of chronic stress on the relative level of dopamine receptor gene expression

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Abstract

Background. The regulation of the central dopaminergic system under the influence of chronic stress is disturbed, however, the dynamics of changes in the dopamine receptors expression in the periphery remains poorly understood.

Aim. Evaluation of the different models of chronic stress influence on changes in the relative level of dopamine receptor gene expression in peripheral blood cells of rats during immobilization and intense physical activity.

Material and methods. For 270 days on 88 Wistar rats, the study on the effect of different models of chronic stress on the change in the relative level of Drd1–5 genes expression was performed in four groups: the first control group; the second group was subjected to intensive physical activity in the “Forced swimming with a load” test (7-minute swimming with a load of 8% of body weight 2 times a week); the third group experienced daily 90-minute immobilization for 14 days; the fourth group had combined exposure of physical activity and immobilization. The relative level of dopamine receptor gene expression was determined by real-time polymerase chain reaction after 90, 180, and 270 days of the experiment in peripheral blood cells of the tail vein. The calculation of the relative level of gene expression was carried out based on the Livak method (2–ΔΔCt); the assessment of the difference significance — using a two-sample t-test for independent samples.

Results. The analysis of the relative level of genes encoding D1-type dopamine receptors expression showed that a decrease in the Drd1 gene expression level after 90 days of the experiment was detected only in male rats from immobilization stress and control groups [RQ 0.35 (p=0.003) and 0.21 (p=0.002), respectively], while in males from other groups and females, the activity of this gene did not change significantly throughout the course of the experiment. The relative expression level of Drd5 gene changed only in female rats. In females subjected to intense physical activity, the level of this gene expression increased almost 4 times (RQ 3.82, p=0.005) 90 days after the start of the experiment, and in females of the control group, the transcriptional activity of the gene decreased 4 times after 180 days of the experiment (RQ 0.25, p=0.015). When assessing changes in the activity of genes encoding D2-type receptors for the Drd3 and Drd4 genes, a significant increase in the relative expression level was revealed in all experimental groups, both in males and females, on the 180th day of exposure to stress factors. At the same time, activation of both genes was occurred after 90 days in the control group only in females and persisted up to another 90 days, after which it returned to the initial level. Expression of the Drd2 gene wasn't detected in rat blood cells.

Conclusion. The relative level of expression of D1- and D2-like receptor genes in rat peripheral blood cells depends on the type of chronic stress and has pronounced sexual dimorphism.

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About the authors

Elena V. Valeeva

Kazan (Volga Region) Federal university; Kazan state medical university

Author for correspondence.
Email: vevaleeva@ya.ru
ORCID iD: 0000-0001-7080-3878
SPIN-code: 4670-8980
Scopus Author ID: 57195580617
ResearcherId: W-8036-2019

Junior Researcher, Central research laboratory, Kazan State Medical University; Assistant, Depart. of Biochemistry, Biotechnology and Pharmacology

Russian Federation, Kazan, Russia; Kazan, Russia

Irina I. Semina

Kazan state medical university

Email: seminai@mail.ru
ORCID iD: 0000-0003-3515-0845

Prof., Depart. of Pharmacology, Head, Central research laboratory

Russian Federation, Kazan, Russia

Antonina G. Galeeva

Kazan (Volga Region) Federal university; Federal Center for toxicological, radiation, and biological safety — Federal Research Veterinary Institute

Email: antonina-95@yandex.ru
ORCID iD: 0000-0003-2650-6459

Cand. Sci. (Vet.), Junior Researcher, Open Lab “Markers of Pathogenesis”; Junior Resear­cher

Russian Federation, ­Kazan, Russia; ­Kazan, Russia

Albina D. Mukhametshina

Kazan (Volga Region) Federal university

Email: albinam1709@gmail.com
ORCID iD: 0000-0002-5296-1861

Bachelor, Depart. of Biochemistry, Biotechnology and Pharmacology

Russian Federation, Kazan, Russia

Regina D. Mukhametshina

Kazan (Volga Region) Federal university

Email: 1709mrd@gmail.com
ORCID iD: 0000-0002-5797-993X

Bachelor, Depart. of Biochemistry, Biotechnology and Pharmacology

Russian Federation, Kazan, Russia

Olga A. Kravtsova

Kazan (Volga Region) Federal university

Email: okravz@yandex.ru
ORCID iD: 0000-0002-4227-008X

Cand. Sci. (Biol.), Assoc. Prof., Depart. of Biochemistry, Biotechnology and Pharmacology

Russian Federation, Kazan, Russia

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2. Рис. 1. Изменение относительного уровня экспрессии гена дофаминового рецептора 1-го типа (Drd1) в крови у самок и самцов крыс в контрольной группе и группах, подвергавшихся физической нагрузке (ФН), иммобилизационному стрессу (ИС) и комбинированному воздействию стрессовых факторов на 90, 180 и 270 сут от начала наблюдения. Уровень р отмечен звёздочкой: *p ≤0,005

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3. Рис. 2. Изменение относительного уровня экспрессии гена дофаминового рецептора 5-го типа (Drd5) в крови у самок и самцов крыс в контрольной группе и группах, подвергавшихся физической нагрузке (ФН), иммобилизационному стрессу (ИС) и комбинированному воздействию стрессовых факторов на 90, 180 и 270 сут от начала наблюдения. Уровень р отмечен звёздочками: *p ≤0,05, **p ≤0,005

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4. Рис. 3. Изменение относительного уровня экспрессии гена дофаминового рецептора 3-го типа (Drd3) в крови у самок и самцов крыс в контрольной группе и группах, подвергавшихся физической нагрузке (ФН), иммобилизационному стрессу (ИС) и комбинированному воздействию стрессовых факторов на 90, 180 и 270 сут от начала наблюдения. Уровень р отмечен звёздочками: *p ≤0,05, **p ≤0,005, ***p ≤0,001

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5. Рис. 4. Изменение относительного уровня экспрессии гена дофаминового рецептора 4-го типа (Drd4) в крови у самок и самцов крыс в контрольной группе и группах, подвергавшихся физической нагрузке (ФН), иммобилизационному стрессу (ИС) и комбинированному воздействию стрессовых факторов на 90, 180 и 270 сут от начала наблюдения. Уровень р отмечен звёздочками: *p ≤0,05, **p ≤0,001, ***p ≤0,0001

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