Search

It is believed that experimental thiamine (vitamin B1) and cholecalciferol (vitamin D3) deficiency in rats is a models of selective neurodegeneration associated with chronic oxidative stress [1]. One of the commonly accepted models of thiamine deficiency is the chronic alcoholism (ChA) model, which we used in this study to test how vitamin D in combination with other drugs affects the functional state of proteins that are components of the cytoskeleton of nerve cells. A model of chronic alcoholism was reproduced on male white rats weighing 150-180 g, which were kept on 15% (vol/vol) aqueous ethanol solution as the only source of drinking water for 9 months. Corrective drugs were administered to experimental rats in the last week of the experiment in the dose (per 100 g of body weight): vitamin D3 - 2.5 μg (100 IU), thiamine - 200 μg, antioxidant drug Metovitan - 2.5 mg in saline suspension [2]. Western blot analysis was used to determine the relative levels of the following proteins in the cortex of rats as markers of neurodegeneration: GFAP (glial fibrillary acidic protein, which serves as a marker of the astrocytes), neurofilament NfH and its phosphorylated form - pNfH (neuron-specific components that maintain structural integrity), tau protein and its phosphorylated form - p-tau (microtubule-associated protein and a biomarker of neurodegenerative diseases). The results of the study indicate the onset of the development of degenerative processes under the conditions of the experimental model. We observed a significant decrease (25%) in GFAP levels in the cortical cells of rats with ChA, which was restored after vitamin B1 and D3 supplementation. Under the same conditions, the level of NfH increased twofold and pNfH almost fourfold as compared with control. Interestingly, in the case of the NfH protein, only the administration of vitamin D3 and, to a lesser extent, vitamin B1 in combination with Metovitan partially reduced the level of this protein, especially its phosphorylated form. The relative levels of tau protein and its phosphorylated form (p-tau) in the cortex of rats with ChA increased about 1.5 times, without any changes after administration of vitamins B1 and D3. Approximation of the relative levels of p-tau to control levels was only observed with a combination of vitamin B1 and Metovitan. The presence of degenerative changes in the cortex of ChA rats was confirmed by histochemical studies. Cortical sections from experimental rats were treated with antibodies against β-tubulin class III protein (reflecting neuronal microtubule status) and DAPI (4′,6-diamidine-2-phenylindole) for nuclear staining. Our study have shown degenerative changes in the brain cortex tissue of rats with ChA. We have found a positive effect of the combination of thiamine with Metovitane and, largely, with vitamin D3, thiamine and Metovitane. The data obtained suggest that vitamin B1 and D3 may have a specific protective effect on the state of neuronal cytoskeletal proteins. Further studies of neuron-specific proteins under conditions of neurodegeneration and mechanisms of the corrective effect of vitamins could be promising. [ABSTRACT FROM AUTHOR]