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Information × Registration Number 0223U005359, 0120U104127 , R & D reports Title Neuroprotective action of vitamin D3 in glucocorticoid-induced neurotoxicity popup.stage_title Head Shymanskyi Ihor O., Кандидат біологічних наук Registration Date 20-12-2023 Organization Palladin Institute of Biochemistry of the National Academy of Sciences of Ukraine popup.description2 An increase in NF-κB transcriptional activity was found in the brain of rats with prednisolone-induced neurotoxicity. We determined the contribution of NF-κB dimers, p50/p65 and p50/c-Rel, with respectively proapoptotic and antiapoptotic functions in neuronal cells, to the development of GC-induced neurotoxicity. An increase in p50/p65 with a decrease in p50/c-Rel has been shown in the cerebral cortex. The administration of a selective NF-κB inhibitor, JSH23, against the background of a glucocorticoid load, decreased the transcriptional activity of NF-κB/p65, which at the cellular level correlated with the inhibition of pro-inflammatory and pro-apoptotic processes in nerve cells of the hippocampus and cerebral cortex. These data indicate a direct involvement of the canonical NF-κB pathway in the development of neuropathological changes associated with long-term prednisone administration. The effects of JSH23 were similar to those of vitamin D3 that may strongly support the role of modulation of NF-κB activity as a key event in the neuroprotective mechanism of action of vitamin D3. In GC-induced neurotoxicity, expression of the cytokine triad RANKL/RANK/OPG was found to be correlated with activation of the NF-κB signaling pathway. We found decreased RANKL content, whereas OPG and RANK levels were elevated in neural tissue. An increase in the steroid receptor ratio (GR/MR) was demonstrated, which correlated with the severity of GC-induced neuropathological changes and insufficient bioavailability of vitamin D. Changes were demonstrated in the content of Ca2+-binding/sensory and neurospecific proteins (S100B, NF-L, MBP and GFAP) and their correlations with the structural and functional state of brain tissue, as well as cognitive-behavioral dysfunction. We established the full or partial corrective effect of vitamin D3 on NF-κB activity, its dimeric composition, the expression of RANKL/RANK/OPG cytokine axis proteins, steroid receptors, Ca2+-binding/sensory and neurospe Product Description popup.authors Isaiev Dmytro S. Bilous Vasil Leonidovych Velykyi Mykola M. Lisakovska Olha O. Labudzynskyi Dmytro O. Khomenko Anna Victororivna popup.nrat_date 2023-12-20 Close