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      Exposure to Inorganic Mercury Causes Oxidative Stress, Cell Death, and Functional Deficits in the Motor Cortex

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          Abstract

          Mercury is a toxic metal that can be found in the environment in three different forms – elemental, organic and inorganic. Inorganic mercury has a lower liposolubility, which results in a lower organism absorption and reduced passage through the blood–brain barrier. For this reason, exposure models that use inorganic mercury in rats in order to evaluate its effects on the central nervous system are rare, especially in adult subjects. This study investigated if a chronic exposure to low doses of mercury chloride (HgCl2), an inorganic form of mercury, is capable of promoting motor alterations and neurodegenerative in the motor cortex of adult rats. Forty animals were exposed to a dose of 0.375 mg/kg/day, for 45 days. They were then submitted to motor evaluation and euthanized to collect the motor cortex. Measurement of mercury deposited in the brain parenchyma, evaluation of oxidative balance, quantification of cellular cytotoxicity and apoptosis and density of mature neurons and astrocytes of the motor cortex were performed. It was observed that chronic exposure to inorganic mercury caused a decrease in balance and fine motor coordination, formation of mercury deposits and oxidative stress verified by the increase of lipoperoxidation and nitrite concentration and a decrease of the total antioxidant capacity. In addition, we found that this model of exposure to inorganic mercury caused cell death by cytotoxicity and induction of apoptosis with a decreased number of neurons and astrocytes in the motor cortex. Our results provide evidence that exposure to inorganic mercury in low doses, even in spite of its poor ability to cross biological barriers, is still capable of inducing motor deficits, cell death by cytotoxicity and apoptosis, and oxidative stress in the motor cortex of adult rats.

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          Environmental Mercury and Its Toxic Effects

          Mercury exists naturally and as a man-made contaminant. The release of processed mercury can lead to a progressive increase in the amount of atmospheric mercury, which enters the atmospheric-soil-water distribution cycles where it can remain in circulation for years. Mercury poisoning is the result of exposure to mercury or mercury compounds resulting in various toxic effects depend on its chemical form and route of exposure. The major route of human exposure to methylmercury (MeHg) is largely through eating contaminated fish, seafood, and wildlife which have been exposed to mercury through ingestion of contaminated lower organisms. MeHg toxicity is associated with nervous system damage in adults and impaired neurological development in infants and children. Ingested mercury may undergo bioaccumulation leading to progressive increases in body burdens. This review addresses the systemic pathophysiology of individual organ systems associated with mercury poisoning. Mercury has profound cellular, cardiovascular, hematological, pulmonary, renal, immunological, neurological, endocrine, reproductive, and embryonic toxicological effects.
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            Plasticity and primary motor cortex.

            One fundamental function of primary motor cortex (MI) is to control voluntary movements. Recent evidence suggests that this role emerges from distributed networks rather than discrete representations and that in adult mammals these networks are capable of modification. Neuronal recordings and activation patterns revealed with neuroimaging methods have shown considerable plasticity of MI representations and cell properties following pathological or traumatic changes and in relation to everyday experience, including motor-skill learning and cognitive motor actions. The intrinsic horizontal neuronal connections in MI are a strong candidate substrate for map reorganization: They interconnect large regions of MI, they show activity-dependent plasticity, and they modify in association with skill learning. These findings suggest that MI cortex is not simply a static motor control structure. It also contains a dynamic substrate that participates in motor learning and possibly in cognitive events as well.
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              [42] Determination of aldehydic lipid peroxidation products: Malonaldehyde and 4-hydroxynonenal

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                Author and article information

                Contributors
                Journal
                Front Mol Neurosci
                Front Mol Neurosci
                Front. Mol. Neurosci.
                Frontiers in Molecular Neuroscience
                Frontiers Media S.A.
                1662-5099
                15 May 2018
                2018
                : 11
                : 125
                Affiliations
                [1] 1Laboratory of Functional and Structural Biology, Institute of Biological Sciences, Federal University of Pará , Belém, Brazil
                [2] 2Laboratory of Ecotoxicology, Institute of Biological Sciences, Federal University of Pará , Belém, Brazil
                [3] 3Laboratório de Cultura de Tecidos e Citogenética, SAMAM, Instituto Evandro Chagas , Ananindeua, Brazil
                [4] 4Laboratory of Molecular Pharmacology, Institute of Biological Sciences, Federal University of Pará , Belém, Brazil
                [5] 5Laboratory of Inflammation and Behavior Pharmacology, Pharmacy Faculty, Institute of Health Science, Federal University of Pará , Belém, Brazil
                Author notes

                Edited by: Andrei Surguchov, University of Kansas Medical Center, United States

                Reviewed by: Anne O. Summers, University of Georgia, United States; Rodrigo A. Cunha, Universidade de Coimbra, Portugal

                *Correspondence: Rafael R. Lima, rafalima@ 123456ufpa.br

                These authors have contributed equally to this work.

                Article
                10.3389/fnmol.2018.00125
                5962769
                29867340
                61babe0b-ecf7-4ade-ba36-0a865962cc6f
                Copyright © 2018 Teixeira, de Oliveira, Leão, Fagundes, Fernandes, Fernandes, da Silva, Amado, Sagica, de Oliveira, Crespo-Lopez, Maia and Lima.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 14 December 2017
                : 29 March 2018
                Page count
                Figures: 10, Tables: 0, Equations: 0, References: 55, Pages: 12, Words: 0
                Categories
                Neuroscience
                Original Research

                Neurosciences
                mercury,mercury chloride,cell death,oxidative stress,motor cortex
                Neurosciences
                mercury, mercury chloride, cell death, oxidative stress, motor cortex

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