Histological and immunohistochemical changes in mouse prefrontal cortex exposed to dexamethasone
Authors:   Institute of Molecular Biology and Biophysics, Federal Research Center for Fundamental and Translational Medicine, Novosibirsk, Sokolov D.K. , Kazanskaya G.M. ,   Institute of Molecular Biology and Biophysics, Federal Research Center for Fundamental and Translational Medicine, Novosibirsk, Volkov A.M. ,   E.N. Meshalkin National Medical Research Centre, Novosibirsk, Strokotova A.V. ,   Institute of Molecular Biology and Biophysics, Federal Research Center for Fundamental and Translational Medicine, Novosibirsk, Kliver E.E. ,   E.N. Meshalkin National Medical Research Centre, Novosibirsk,   Novosibirsk State Medical University, Novosibirsk, Grigorieva E.V. ,   Institute of Molecular Biology and Biophysics, Federal Research Center for Fundamental and Translational Medicine, Novosibirsk, Aidagulova S.V. ,   Institute of Molecular Biology and Biophysics, Federal Research Center for Fundamental and Translational Medicine, Novosibirsk,   Novosibirsk State Medical University, Novosibirsk
Published: September 2024

Introduction. The effects of the synthetic glucocorticoid dexamethasone on target organs are mediated by the interaction with the glucocorticoid receptor, but the effects of the drug on the intact brain have been poorly studied. We aimed to look at a one-time and repeated exposure to a two-dose dexamethasone on the expression of the glucocorticoid receptor and cellular changes in the prefrontal cortex over time. Materials and methods. Male C57Bl/6 mice aged 7–8 weeks received a one-time or multiple intraperitoneal injections of dexamethasone in doses of 1.0 or 2.5 mg/kg. Structural changes in the prefrontal cortex were analyzed on paraffin sections stained by hematoxylin and eosin 90 days after the injection. The expression of the glucocorticoid receptor was studied with immunohistochemistry using monoclonal antibodies and quantitative analysis. Results. A histological study of the prefrontal cortex exposed to a two-dose dexamethasone revealed the absence of an obvious dose dependence and the reversibility of dystrophic and hydropic changes. The most pronounced changes were revealed with a one-time administration of the drug (on day 7) and repeated administration (on day 15) while normal tissue architecture returned to that of the control groups. The expression level of the glucocorticoid receptor after a one-time dexamethasone injection at a dose of 2.5 mg/kg showed a significant growth (р<0.05) on days 3 and 10 compared to that of the control group, while after multiple dexamethasone injections, the GR expression decreased on day 15, but by day 30 it returned to its initial level. Conclusion. Stereotypical dystrophic and hydropic changes in the prefrontal cortex during exposure to two different regimens and dexamethasone doses developed on days 7 and 15. We revealed an opposite effect of 2.5 mg/kg dexamethasone administration regimens on the expression of the glucocorticoid receptor in the prefrontal cortex of mice relative to the control group: at a one-time administration the expression increased by 8.1% on day 10 and at multiple administration the expression grew by 9.9% on day 15. Keywords: dexamethasone, glucocorticoids, brain, prefrontal cortex, glucocorticoid receptor, immunohistochemistry