Multiple Administration of Dexamethasone Possesses a Deferred Long-Term Effect to Glycosylated Components of Mouse Brain.

Autor: Aladev SD; Institute of Molecular Biology and Biophysics FRC FTM, Novosibirsk 630117, Russia., Sokolov DK; Institute of Molecular Biology and Biophysics FRC FTM, Novosibirsk 630117, Russia., Strokotova AV; Institute of Molecular Biology and Biophysics FRC FTM, Novosibirsk 630117, Russia., Kazanskaya GM; Institute of Molecular Biology and Biophysics FRC FTM, Novosibirsk 630117, Russia.; E.N. Meshalkin National Medical Research Center, Novosibirsk 630055, Russia., Volkov AM; E.N. Meshalkin National Medical Research Center, Novosibirsk 630055, Russia., Aidagulova SV; Institute of Molecular Biology and Biophysics FRC FTM, Novosibirsk 630117, Russia.; Laboratory of Cellular Biology, Novosibirsk State Medical University, Novosibirsk 630091, Russia., Grigorieva EV; Institute of Molecular Biology and Biophysics FRC FTM, Novosibirsk 630117, Russia.
Jazyk: angličtina
Zdroj: Neurology international [Neurol Int] 2024 Jul 22; Vol. 16 (4), pp. 790-803. Date of Electronic Publication: 2024 Jul 22.
DOI: 10.3390/neurolint16040058
Abstrakt: Glucocorticoids are used during glioblastoma treatment to prevent the cerebral edema effect surrounding normal brain tissue. The aim of our study was to investigate the long-term effects of multiple administrations of glucocorticoids onto the glycosylated components (proteoglycans and glycosaminoglycans) of normal brain extracellular matrix and the glucocorticoid receptor (GR, Nr3c1 ) in an experimental model in vivo . Two-month-old male C57Bl/6 mice (n = 90) were injected intraperitoneally with various doses of dexamethasone (DXM) (1; 2.5 mg/kg) for 10 days. The mRNA levels of the GR, proteoglycans core proteins, and heparan sulfate metabolism-involved genes were determined at the 15th, 30th, 60th, and 90th days by a real-time RT-PCR. The glycosaminoglycans content was studied using dot blot and staining with Alcian blue. A DXM treatment increased total GAG content (2-fold), whereas the content of highly sulfated glycosaminoglycans decreased (1.5-2-fold). The mRNA level of the heparan sulfate metabolism-involved gene Hs3St2 increased 5-fold, the mRNA level of Hs6St2 increased6-7-fold, and the mRNA level of proteoglycan aggrecan increased 2-fold. A correlation analysis revealed an association between the mRNA level of the GR and the mRNA level of 8 of the 14 proteoglycans-coding and 4 of the 13 heparan sulfate metabolism-involved genes supporting GR involvement in the DXM regulation of the expression of these genes. In summary, multiple DXM administrations led to an increase in the total GAG content and reorganized the brain extracellular matrix in terms of its glycosylation pattern.
Databáze: MEDLINE
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