Long-term Intracerebroventricular Administration of Ouabain Causes Motor Impairments in C57Bl/6 Mice
- Authors: Timoshina Y.A.1,2, Kazanskaya R.B.3,2, Zavialov V.A.3, Volnova A.B.3, Latanov A.V.1, Fedorova T.N.2, Gainetdinov R.R.3, Lopachev A.V.3,2
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Affiliations:
- Lomonosov Moscow State University
- Research Center of Neurology
- Saint Petersburg State University
- Issue: Vol 17, No 4 (2023)
- Pages: 40-51
- Section: Original articles
- URL: https://journals.rcsi.science/2075-5473/article/view/251938
- DOI: https://doi.org/10.54101/ACEN.2023.4.5
- ID: 251938
Cite item
Abstract
Introduction. Cardiac glycosides are natural ligands of Na+/K+-ATPase, which regulate its activity and signaling. Intracerebroventricular administration of ouabain has been previously shown to induce hyperlocomotion in C57Bl/6 mice via a decrease in the rate of dopamine reuptake from the synaptic cleft.
Materials and methods. This study involved forty C57BL/6 mice. 1.5 μL of 50 μM ouabain was administered daily into the left lateral cerebral ventricle over the course of 4 days. On day 5, open field, beam balance, and ladder rung walking tests were performed to assess the locomotor activity and motor impairments in the mice. We evaluated changes in the activation of signaling cascades, ratios of proapoptotic and antiapoptotic proteins, and the amount of α1 and α3 isoforms of the Na+/K+-ATPase α-subunit in brain tissue using Western blotting. Na+/K+-ATPase activity was evaluated in the crude synaptosomal fractions of the brain tissues.
Results. We observed hyperlocomotion and stereotypic behavior during the open field test 24 hours after the last injection of ouabain. On day 5, the completion time and the number of errors made in the beam balance and ladder rung walking tests increased in the mice that received ouabain. Akt kinase activity decreased in the striatum, whereas the ratio of proapoptotic and antiapoptotic proteins and the number of Na+/K+-ATPase α-subunits did not change. Na+/K+-ATPase activity increased in the striatum and decreased in the brainstem.
Conclusions. Long-term exposure to ouabain causes motor impairments mediated by changes in the activation of signaling cascades in dopaminergic neurons.
Keywords
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##article.viewOnOriginalSite##About the authors
Yulia A. Timoshina
Lomonosov Moscow State University; Research Center of Neurology
Email: july.timoschina@yandex.ru
ORCID iD: 0000-0002-0546-8767
Rogneda B. Kazanskaya
Saint Petersburg State University; Research Center of Neurology
Email: st059046@student.spbu.ru
ORCID iD: 0000-0002-2194-6749
Postgraduate Student, Faculty of Biology, Saint Petersburg State University; Research Laboratory Assistant, Laboratory of Experimental and Translational Neurochemistry, Brain Science Institute, Research Center of Neurology
Russian Federation, St. Petersburg; MoscowVladislav A. Zavialov
Saint Petersburg State University
Email: vladislavletsgo@outlook.com
ORCID iD: 0009-0000-6576-3373
Graduate Student, Laboratory Assistant, Laboratory of Neurobiology and Molecular Pharmacology, Institute of Translational Biomedicine
Russian Federation, St. PetersburgAnna B. Volnova
Saint Petersburg State University
Email: a.volnova@spbu.ru
ORCID iD: 0000-0003-0724-887X
D. Sci. (Biol.), Senior Researcher, Department of General Physiology, Biolodical Department
Russian Federation, St. PetersburgAlexander V. Latanov
Lomonosov Moscow State University
Email: latanov@neurobiology.ru
ORCID iD: 0000-0003-2729-4013
D. Sci. (Biol.), Prof., Head, Department of Higher Nervous Activity, Faculty of Biology
Russian Federation, MoscowTatiana N. Fedorova
Research Center of Neurology
Email: tnf51@bk.ru
ORCID iD: 0000-0002-0483-1640
D. Sci. (Biol.), Head, Laboratory of Experimental and Translational Neurochemistry, Brain Science Institute
Russian Federation, MoscowRaul R. Gainetdinov
Saint Petersburg State University
Email: gainetdinov.raul@gmail.com
ORCID iD: 0000-0003-2951-6038
Cand. Sci. (Med.), Head, Laboratory of Neurobiology and Molecular Pharmacology, Scientific Director, Clinic of High Medical Technologies named after N.I. Pirogov, Director, Institute of Translational Biomedicine
Russian Federation, St. PetersburgAlexander V. Lopachev
Saint Petersburg State University; Research Center of Neurology
Author for correspondence.
Email: lopachev@neurology.ru
ORCID iD: 0000-0002-5688-3899
Cand. Sci. (Biol.), Researcher, Laboratory of Experimental and Translational Neurochemistry, Brain Science Institute, Research Center of Neurology; Researcher, Laboratory of Neurobiology and Molecular Pharmacology, Saint Petersburg State University
Russian Federation, St. Petersburg; MoscowReferences
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