Dexamethasone Effects on Cell Composition and Myelin Content in the Mouse Brain

Background: Glucocorticoids are used as anti-inflammatory drugs for the treatment of various diseases, however, their side effects on normal brain tissue remain underinvestigated. Objectives: The study aimed to investigate dexamethasone (DXM) effects on cell composition and myelin content in the mouse brain tissue. Methods: C57Bl/6 male mice (n = 60) received single and ten multiple intraperitoneal DXM injections (2.5 mg/kg), and the studied parameters were analysed at 1, 3, 7, 10 days after a single DXM injection and 15, 30, 60, and 90 days after the multiple injections. Oligodendrocytes, microglia, and astrocytes were assayed by immunohistochemistry with specific antibodies (Olig2, CD68, and GFAP, respectively) in the corpus callosum of the normal brain tissue. The myelin content was estimated by staining with LuxolFastBlue. The presence of GFAP isoforms was determined by western blotting. Results: DXM administration did not affect oligodendrocytes in the mouse brain but temporarily significantly decreased myelin content (1.2-fold, p = 0.0058; 1.4-fold, p < 0.0001) at 3–15 days time points. At the same time, DXM significantly decreased the number of microglial cells (1.5–3.5-fold, p < 0.0001) and significantly increased astrocytes (1.8-fold, p < 0.0001). Prolonged administration of DXM resulted in the decrease of the main GFAP α-isoform (50 kDa) and the appearance of shorter GFAP isoforms (30 kDa, 42 kDa, 44 kDa) similar to that in some neurodegenerative animal models. Conclusion: DXM can modify the cell composition of the normal mouse brain tissue by decreasing microglial cells and increasing astrocytes. Long-term use of DXM results in the inhibition of myelin formation and the appearance of truncated GFAP isoforms, suggesting its ability to induce neurodegeneration-like changes in the normal mouse brain.