VITAMIN D3 AFFECTS GLUCOCORTICOID-SENSITIVE RECEPTORS AND BRAIN-DERIVED NEUROTROPHIC FACTOR IN PREDNISOLONE-INDUCED NEUROTOXICITY

Aim. The study aimed to explore the effects of vitamin D3 (D3) on markers of brain tissue metabolism in prednisolone-induced neurotoxicity in rats. Methods. Female Wistar rats received prednisolone (5 mg/kg of b.w.) with or without D3 (1000 IU/kg of b.w.) for 30 days. Serum 25-hydroxyvitamin D3 (25D3) and brain tissue BDNF levels were measured by ELISA. We used western blotting to determine levels of glucocorticoid-sensitive receptors: GRα/β (glucocorticoid receptor) and MR (mineralocorticoid receptor). The number of astrocytes in histological sections of the cerebral cortex and hippocampus CA1-CA3 regions was assessed by immunofluorescent labeling of the macroglial marker protein GFAP (glial fibrillary acidic protein). Data were statistically analyzed using one-way ANOVA followed by Tukey's test. The significant level was set at P < 0.05. Results. Long-term administration of prednisolone decreased serum and brain tissue 25D3 levels and increased the GR/MR ratio, suggesting a potential neurotoxic effect. It also increased brain tissue BDNF levels and astrocyte numbers in histological sections of rats` brains. D3 supplementation completely or partially reversed the alterations, elucidating its neuroprotective effect. Conclusions. The study suggests that D3 deficiency may contribute to neuropathological changes induced by long-term exposure to prednisolone. Based on the identified positive effects of D3 on the CNS, its practical usefulness in the complex treatment of neurological and cognitive disorders associated with GC-based therapeutics can be envisaged.