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      Subchronic Arsenic Exposure Induces Anxiety-Like Behaviors in Normal Mice and Enhances Depression-Like Behaviors in the Chemically Induced Mouse Model of Depression

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          Abstract

          Accumulating evidence implicates that subchronic arsenic exposure causes cerebral neurodegeneration leading to behavioral disturbances relevant to psychiatric disorders. However, there is still little information regarding the influence of subchronic exposure to arsenic-contaminated drinking water on mood disorders and its underlying mechanisms in the cerebral prefrontal cortex. The aim of this study is to assess the effects of subchronic arsenic exposure (10 mg/LAs2O3 in drinking water) on the anxiety- and depression-like behaviors in normal mice and in the chemically induced mouse model of depression by reserpine pretreatment. Our findings demonstrated that 4 weeks of arsenic exposure enhance anxiety-like behaviors on elevated plus maze (EPM) and open field test (OFT) in normal mice, and 8 weeks of arsenic exposure augment depression-like behaviors on tail suspension test (TST) and forced swimming test (FST) in the reserpine pretreated mice. In summary, in this present study, we demonstrated that subchronic arsenic exposure induces only the anxiety-like behaviors in normal mice and enhances the depression-like behaviors in the reserpine induced mouse model of depression, in which the cerebral prefrontal cortex BDNF-TrkB signaling pathway is involved. We also found that eight weeks of subchronic arsenic exposure are needed to enhance the depression-like behaviors in the mouse model of depression. These findings imply that arsenic could be an enhancer of depressive symptoms for those patients who already had the attribute of depression.

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          Most cited references46

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          The tail suspension test: a new method for screening antidepressants in mice.

          A novel test procedure for antidepressants was designed in which a mouse is suspended by the tail from a lever, the movements of the animal being recorded. The total duration of the test (6 min) can be divided into periods of agitation and immobility. Several psychotropic drugs were studied: amphetamine, amitriptyline, atropine, desipramine, mianserin, nomifensine and viloxazine. Antidepressant drugs decrease the duration of immobility, as do psychostimulants and atropine. If coupled with measurement of locomotor activity in different conditions, the test can separate the locomotor stimulant doses from antidepressant doses. Diazepam increases the duration of immobility. The main advantages of this procedure are the use of a simple, objective test situation, the concordance of the results with the validated "behavioral despair" test from Porsolt and the sensitivity to a wide range of drug doses.
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            Neuroimaging and neuropathological studies of depression: implications for the cognitive-emotional features of mood disorders.

            Neuroimaging technology has provided unprecedented opportunities for elucidating the anatomical correlates of major depression. The knowledge gained from imaging research and from the postmortem studies that have been guided by imaging data is catalyzing a paradigm shift in which primary mood disorders are conceptualized as illnesses that involve abnormalities of brain structure, as well as of brain function. These data suggest specific hypotheses regarding the neural mechanisms underlying pathological emotional processing in mood disorders. They particularly support a role for dysfunction within the prefrontal cortical and striatal systems that normally modulate limbic and brainstem structures involved in mediating emotional behavior in the pathogenesis of depressive symptoms.
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              Elevated Plus Maze for Mice

              Although the mouse genome is now completely sequenced, the functions of most of the genes expressed in the brain are not known. The influence of a given gene on a specific behavior can be determined by behavioral analysis of mutant mice. If a target gene is expressed in the brain, behavioral phenotype of the mutant mice could elucidate the genetic mechanism of normal behaviors. The elevated plus maze test is one of the most widely used tests for measuring anxiety-like behavior. The test is based on the natural aversion of mice for open and elevated areas, as well as on their natural spontaneous exploratory behavior in novel environments. The apparatus consists of open arms and closed arms, crossed in the middle perpendicularly to each other, and a center area. Mice are given access to all of the arms and are allowed to move freely between them. The number of entries into the open arms and the time spent in the open arms are used as indices of open space-induced anxiety in mice. Unfortunately, the procedural differences that exist between laboratories make it difficult to duplicate and compare results among laboratories. Here, we present a detailed movie demonstrating our protocol for the elevated plus maze test. In our laboratory, we have assessed more than 90 strains of mutant mice using the protocol shown in the movie. These data will be disclosed as a part of a public database that we are now constructing. Visualization of the protocol will promote better understanding of the details of the entire experimental procedure, allowing for standardization of the protocols used in different laboratories and comparisons of the behavioral phenotypes of various strains of mutant mice assessed using this test.
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                Author and article information

                Journal
                Biomed Res Int
                Biomed Res Int
                BMRI
                BioMed Research International
                Hindawi Publishing Corporation
                2314-6133
                2314-6141
                2015
                31 May 2015
                : 2015
                : 159015
                Affiliations
                1Department of Neurology, Chi Mei Medical Center, 901 Chung-Hwa Road, Yongkang, Tainan 710, Taiwan
                2Department of Biotechnology, College of Engineering, Southern Taiwan University of Science and Technology, 1 Nan-Tai Street, Yongkang, Tainan 710, Taiwan
                3Department of Occupational and Environmental Medicine, National Cheng Kung University Hospital, 138 Sheng-Li Road, Tainan 704, Taiwan
                4Department of Environmental and Occupational Health, College of Medicine, National Cheng Kung University, 138 Sheng-Li Road, Tainan 704, Taiwan
                5Occupational Safety, Health, and Medicine Research Center, National Cheng Kung University, 138 Sheng-Li Road, Tainan 704, Taiwan
                6Center for Occupational and Environmental Health and Preventive Medicine, National Cheng Kung University, 138 Sheng-Li Road, Tainan 704, Taiwan
                7Department of Occupational Medicine, Chi Mei Medical Center, 901 Chung-Hwa Road, Yongkang, Tainan 710, Taiwan
                8Department of Occupational Safety and Health, Institute of Industrial Safety and Disaster Prevention, College of Sustainable Environment, Chia Nan University of Pharmacy and Science, No. 60, Section 1, Erh-Jen Road, Jen-Te, Tainan 711, Taiwan
                Author notes

                Academic Editor: Damião Pergentino de Sousa

                Author information
                http://orcid.org/0000-0002-8332-3993
                http://orcid.org/0000-0003-1289-8412
                Article
                10.1155/2015/159015
                4465655
                cbe9e804-181c-4256-83ae-41aa12f93d5e
                Copyright © 2015 Chia-Yu Chang et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 2 December 2014
                : 5 April 2015
                : 21 April 2015
                Categories
                Research Article

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