Impact of manganese accumulation on Na,K-ATPase expression and function in the cerebellum and striatum of C57Bl/6 mice.

Autor: Smolyaninova LV; Laboratory of Biological Membranes, Faculty of Biology, Lomonosov Moscow State University, 119991 Moscow, Russia. Electronic address: smolyaninovalarisa1@gmail.com., Timoshina YA; Department of Higher Nervous Activity, Faculty of Biology, Lomonosov Moscow State University, 119991 Moscow, Russia; Laboratory of Experimental and Translational Neurochemistry, Research Center of Neurology, Volokolamskoe Shosse, 80, Moscow 125367, Russia., Berezhnoy DS; Department of Higher Nervous Activity, Faculty of Biology, Lomonosov Moscow State University, 119991 Moscow, Russia; Laboratory of Experimental and Translational Neurochemistry, Research Center of Neurology, Volokolamskoe Shosse, 80, Moscow 125367, Russia., Fedorova TN; Laboratory of Experimental and Translational Neurochemistry, Research Center of Neurology, Volokolamskoe Shosse, 80, Moscow 125367, Russia., Mikheev IV; Faculty of Chemistry, Lomonosov Moscow State University, 119991 Moscow, Russia., Seregina IF; Faculty of Chemistry, Lomonosov Moscow State University, 119991 Moscow, Russia., Loginova NA; Research Institute of Higher Nervous Activity and Neurophysiology, Russian Academy of Sciences, 117485 Moscow, Russia., Dobretsov MG; Institute of Evolutionary Physiology and Biochemistry RAS, 194223 St., Petersburg, Russia. Electronic address: dobretsovmaxim@gmail.com.
Jazyk: angličtina
Zdroj: Neurotoxicology [Neurotoxicology] 2023 Sep; Vol. 98, pp. 86-97. Date of Electronic Publication: 2023 Aug 19.
DOI: 10.1016/j.neuro.2023.08.002
Abstrakt: Overexposure to Mn causes a neurological disorder-manganism-with motor symptoms that overlap closely with disorders associated with haploinsufficiency in the gene encoding for α 3 isoform of Na + ,K + -ATPase (NKA). The present study was designed to test the hypothesis that behavioral changes in the mouse model of manganism may be associated with changes in the expression and activity of α 3 NKA in the cerebellum (CB) and striatum (STR)-the key brain structures responsible for motor control in adult mice. C57Bl/6 mice were exposed to MnCl 2 at 0.5 g/L (in drinking water) for up to eight weeks. After four weeks of Mn consumption, Mn levels were increased in the CB only. Behavioral tests demonstrated decreased performance of Mn-treated mice in the shuttle box test (third through sixth weeks), and the inclined grid walking test (first through sixth weeks), suggesting the development of learning impairment, decreased locomotion, and motor discoordination. The activity of NKA significantly decreased, and the expression of α1-α3 isoforms of NKA increased in the second week in the CB only. Thus, signs of learning and motor disturbances developing in this model of manganism are unlikely to be directly linked to disturbances in the expression or activity of NKA in the CB or STR. Whether these early changes may contribute to the pathogenesis of later behavioral deficits remains to be determined.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2023 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE