ROLE OF HYPOXIA AND MITOCHONDRIAL DYSFUNCTION IN THE MECHANISM OF THE EXPERIMENTAL ALZHEIMER’S TYPE DEMENTIA INDUCED BY DIFFERENT WAYS IN RATS AND ASSESSMENT OF POSSIBILITIES TO CORRECT THIS CONDITION BY USING MESENCHYMAL STEM CELLS

Zorenko Y. M., Pavlova O. O., Gorbach T. V., Martynova S. M.

CLINICAL AND EXPERIMENTAL MEDICINE

Scentific article

Abstract. Introduction. It is known that the synaptic dysfunction a key to many neurodegenerative diseases, including Alzheimer’s disease. It has been shown that not only amyloid plaques but also hypoxia and mitochondrial dysfunction are crucialfor the synaptic dysfunction. At the same time, it is poorly known the role of these factors in the mechanisms of Alzheimer’s type dementia of various origins. The aim of the study: to determinate the role of hypoxia and mitochondrial dysfunction in the mechanisms of the experimental Alzheimer’s type dementia development induced by different ways in rats, as well as the possibility of correction of this condition by mesenchymal stem cells. Materials and methods. 32 male WAG rats weighing 180-250 g (n=8 in each group) for 14 and 28 days received intraperitoneal injections of an aqueous solution of sodium nitrite at a dose of 50 mg/kg (gr. N-14, N-28with nitrite-induced dementia) and a solution of scopolamine butylbromide at a dose of 1 m/ kg (gr. SC-14, SC-28 with scopolamine-induced dementia). Other 32 male rats of gr.NS-14, NS-28, SCS-14, SCS-28 were intravenously administered with mesenchymal stem cells (MSCs) after injections of sodium nitrite and scopolamine. Control rats (gr.C, n=16) received sodium chloride injections according to the same experimental design. Rats were sacrificed 14 days after the last injection of MSCs. The concentration of 2,3-diphosphoglycerate in blood erythrocytes (2,3-DFG, μmol/l), acetylcholine (AСh, μg/g) and ATP (μmol/g) - in brain homogenates, cardiolipin (nmol/mg protein) – in mitochondria of brain tissue were determined by using spectrophotometer. Results. The level of 2,3-DFG (nitrite model) was dose-dependently increased in rats gr. N-14, N-28.In rats with scopolamine-induced dementia, an increase in this indicator was observed only twice in gr. SC-28 in comparison with gr. C, but was less pronounced than in gr. N-28. The ATP and cardiolipin concentration in all experimental groups was reduced compared to gr. C. It should be noted that in gr. N-14, N-28 the cardiolipin content in mitochondria was significantly lower than in gr. SC-14, SC-28. The ACh level in gr. N-14, N-28, SC-14 almost did not change, while in gr. SC-28 was reduced as much as possible compared to that in gr. C. The introduction of MSCs improved energy metabolism, reduced hypoxia, normalized the Ach level, but the cardiolipin content was not restored to the control level. Conclusions. A common factor in the pathogenesis of both studied models was mitochondrial dysfunction. The initial factor of mitochondrial dysfunction in the nitrite model was hemic hypoxia and endothelial dysfunction, and in scopolamine - acetylcholine deficiency with subsequent amyloid deposition in brain tissue and blood vessels. Correction of Alzheimer’s type dementia of various genesis is possible with the mesenchymal stem cells introduction. Intravenous administration of MSCs improved mitochondrial function, but without their full recovery.

dementia, hypoxia, mitochondria, stem cells, rats.

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«Bulletin of problems biology and medicine» Issue 1 (159), 2021 year, 66-72 pages, index UDK 616.89-008.454-001.8-092.9-08:602.9:591.476

10.29254/2077-4214-2021-1-159-66-72