Long-term Intracerebroventricular Administration of Ouabain Causes Motor Impairments in C57Bl/6 Mice

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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.

作者简介

Yulia Timoshina

Lomonosov Moscow State University; Research Center of Neurology

Email: july.timoschina@yandex.ru
ORCID iD: 0000-0002-0546-8767

Postgraduate Student, Department of Higher Nervous Activity, Faculty of Biology, Lomonosov Moscow State University; Junior Researcher, Laboratory of Experimental and Translational Neurochemistry, Brain Science Institute, Research Center of Neurology
 
 
 
俄罗斯联邦, Moscow; Moscow

Rogneda 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

俄罗斯联邦, St. Petersburg; Moscow

Vladislav 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

俄罗斯联邦, St. Petersburg

Anna 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

俄罗斯联邦, St. Petersburg

Alexander 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

俄罗斯联邦, Moscow

Tatiana 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

俄罗斯联邦, Moscow

Raul 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

俄罗斯联邦, St. Petersburg

Alexander Lopachev

Saint Petersburg State University; Research Center of Neurology

编辑信件的主要联系方式.
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

俄罗斯联邦, St. Petersburg; Moscow

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