Dexamethasone effects on the expression and content of glycosylated components of mouse brain tissue

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Abstract

Introduction. Glucocorticoids are actively used in the treatment of various diseases, however their long-term use leads to numerous negative side-effects, the molecular mechanisms of which remain poorly understood.

Aim. Study of the short-term (1–10 days) effects of various doses of dexamethasone (Dex) (0,1–10 mg/kg) on the expression of the glucocorticoid receptor (GR, Nr3c1), core proteins of main proteoglycans and heparan sulfate metabolism-involved genes, as well as the content of carbohydrate macromolecules of glycosaminoglycans in the brain tissue of experimental animals.

Materials and methods. In the study, C57Bl/6 mice were used. The expression of GR, proteoglycan core proteins and heparan sulfate metabolism-involved genes was determined by real-time polymerase chain reaction with reverse transcription. The content and localization of GR protein molecule were studied by Western blot and immunohistochemical analysis, and the glycosaminoglycan content was determined by dot-blot analysis and Alcian Blue staining.

Results. It was shown that a single Dex administration leads to fast (1–3 days) short-term activation of GR expression (+1.5 times, p <0.05), proteoglycan’s genes (syndecan-3, Sdc3; perlecan, Hspg2; phosphacan, Ptprz1; neurocan, Ncan; +2–3-fold; p <0.05) and heparan sulfate-metabolism-involved genes (Ndst1, Glce, Hs2st1, Hs6st1, Sulf1 / 2; +1.5–2-fold; p <0.05) in the mouse brain, with a return to control values by 7–10 days after Dex administration. At the same time, the effect of Dex on carbohydrate macromolecules of glycosaminoglycans was more delayed and stable, increasing the content of low-sulfated glycosaminoglycans in the brain tissue in a dose-dependent manner starting from day 1 after Dex administration. Highly-sulfated glycosaminoglycans showed more delayed response to Dex administration, and an increase in their content was observed only at higher doses (2.5 and 10 mg/kg) and only on 7–10 days after its administration, apparently, mainly due to an increase in heparan sulfate content.

Conclusion. In general, the effect of a single injection of Dex on the transcriptional activity of GR, proteoglycan core proteins and heparan sulfate metabolism-involved genes were short-termed, and the genes expression quickly returned to the normal levels. However, even a single use of Dex significantly increased the content of total as well as highly sulfated glycosaminoglycans in the mouse brain tissue, which can lead to the changes in the composition and structure of the brain tissue, as well as its functional characteristics.

About the authors

S. D. Aladev

Institute of Molecular Biology and Biophysics of the Federal Research Center for Fundamental and Translational Medicine, Ministry of Science and Higher Education of the Russian Federation

Author for correspondence.
Email: s.aladev@alumni.nsu.ru
ORCID iD: 0000-0001-5883-4831

 Stanislav Dmitrievich Aladev

2/12 Timakova St., Novosibirsk 630117

Russian Federation

D. K. Sokolov

Institute of Molecular Biology and Biophysics of the Federal Research Center for Fundamental and Translational Medicine, Ministry of Science and Higher Education of the Russian Federation

Email: fake@neicon.ru
ORCID iD: 0000-0002-4145-5277

2/12 Timakova St., Novosibirsk 630117

Russian Federation

A. V. Strokotova

Institute of Molecular Biology and Biophysics of the Federal Research Center for Fundamental and Translational Medicine, Ministry of Science and Higher Education of the Russian Federation

Email: fake@neicon.ru
ORCID iD: 0000-0001-5336-8552

2/12 Timakova St., Novosibirsk 630117

Russian Federation

G. M. Kazanskaya

Institute of Molecular Biology and Biophysics of the Federal Research Center for Fundamental and Translational Medicine, Ministry of Science and Higher Education of the Russian Federation

Email: fake@neicon.ru
ORCID iD: 0000-0003-2598-1805

2/12 Timakova St., Novosibirsk 630117

Russian Federation

A. M. Volkov

E.N. Meshalkin National Medical Research Center

Email: fake@neicon.ru
ORCID iD: 0000-0001-9697-7091

15 Rechkunovskaya St., Novosibirsk 630055

Russian Federation

M. O. Politko

Institute of Molecular Biology and Biophysics of the Federal Research Center for Fundamental and Translational Medicine, Ministry of Science and Higher Education of the Russian Federation

Email: fake@neicon.ru
ORCID iD: 0000-0002-9650-9877

2/12 Timakova St., Novosibirsk 630117

Russian Federation

A. I. Shahmuradova

Institute of Molecular Biology and Biophysics of the Federal Research Center for Fundamental and Translational Medicine, Ministry of Science and Higher Education of the Russian Federation;

Email: fake@neicon.ru

2/12 Timakova St., Novosibirsk 630117

Russian Federation

E. E. Kliver

E.N. Meshalkin National Medical Research Center

Email: fake@neicon.ru
ORCID iD: 0000-0002-3915-3616

15 Rechkunovskaya St., Novosibirsk 630055

Russian Federation

A. Y. Tsidulko

Institute of Molecular Biology and Biophysics of the Federal Research Center for Fundamental and Translational Medicine, Ministry of Science and Higher Education of the Russian Federation

Email: fake@neicon.ru
ORCID iD: 0000-0002-1056-020X

2/12 Timakova St., Novosibirsk 630117

Russian Federation

S. V. Aidagulova

Institute of Molecular Biology and Biophysics of the Federal Research Center for Fundamental and Translational Medicine, Ministry of Science and Higher Education of the Russian Federation; Novosibirsk State Medical University

Email: fake@neicon.ru
ORCID iD: 0000-0001-7124-1969

2/12 Timakova St., Novosibirsk 630117

52 Krasnyi Prospect, Novosibirsk 630091

Russian Federation

E. V. Grigorieva

Institute of Molecular Biology and Biophysics of the Federal Research Center for Fundamental and Translational Medicine, Ministry of Science and Higher Education of the Russian Federation

Email: fake@neicon.ru
ORCID iD: 0000-0003-2457-9179

2/12 Timakova St., Novosibirsk 630117

Russian Federation

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