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Effect of handling on ATP utilization of cerebral Na,K-ATPase in rats with trimethyltin-induced neurodegeneration

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Previously it was shown that for reduction of anxiety and stress of experimental animals, preventive handling seems to be one of the most effective methods. The present study was oriented on Na,K-ATPase, a key enzyme for maintaining proper concentrations of intracellular sodium and potassium ions. Malfunction of this enzyme has an essential role in the development of neurodegenerative diseases. It is known that this enzyme requires approximately 50% of the energy available to the brain. Therefore in the present study utilization of the energy source ATP by Na,K-ATPase in the frontal cerebral cortex, using the method of enzyme kinetics was investigated. As a model of neurodegeneration treatment with trimethyltin (TMT) was applied. Daily handling (10 min/day) of healthy rats and rats suffering neurodegeneration induced by administration of TMT in a dose of (7.5 mg/kg), at postnatal days 60–102 altered the expression of catalytic subunits of Na,K-ATPase as well as kinetic properties of this enzyme in the frontal cerebral cortex of adult male Wistar rats. In addition to the previously published beneficial effect on spatial memory, daily treatment of rats was accompanied by improved maintenance of sodium homeostasis in the frontal cortex. The key system responsible for this process, Na,K-ATPase, was able to utilize better the energy substrate ATP. In rats, manipulation of TMT-induced neurodegeneration promoted the expression of the α2 isoform of the enzyme, which is typical for glial cells. In healthy rats, manipulation was followed by increased expression of the α3 subunit, which is typical of neurons.

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Data availability

The datasets generated during and/or analyzed during the current study are not publicly available but are available from the corresponding author on reasonable request.


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The study was supported by Slovak Grant Agency: VEGA-2/0166/17, VEGA-2/0120/19, VEGA 2/0063/18, and ITMS-26230120006.

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Authors and Affiliations



ZG designed the study; VNS, DM, and EU performed the biological model; BK, NV, DS, and JV performed the analysis and evaluation of Na,K-ATPase expression and estimation of ATP utilization by Na,K-ATPase using the method of enzyme kinetics; ZG, BK, DS, and NV prepared the manuscript.

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Correspondence to Norbert Vrbjar.

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No conflicts of interest, financial, or otherwise are declared by the authors.

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All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. All procedures with animals were performed in compliance with principles of laboratory animal care issued by EU Directive 2010/63/EU for animal experiments, proved and controlled by the State Veterinary and Food Administration of Slovak Republic (No. 4030/10-221), and with the agreement of the Ethical Committee of the Center of Experimental Medicine, Slovak Academy of Sciences. This article does not contain any studies involving human participants performed by any of the authors.

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Kalocayova, B., Snurikova, D., Vlkovicova, J. et al. Effect of handling on ATP utilization of cerebral Na,K-ATPase in rats with trimethyltin-induced neurodegeneration. Mol Cell Biochem 476, 4323–4330 (2021).

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