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      Early Postnatal Manganese Exposure Causes Lasting Impairment of Selective and Focused Attention and Arousal Regulation in Adult Rats

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          Abstract

          Background:

          Studies in children and adolescents have associated early developmental manganese (Mn) exposure with inattention, impulsivity, hyperactivity, and oppositional behaviors, but causal inferences are precluded by the correlational nature of the data and generally limited control for potential confounders.

          Objectives:

          To determine whether early postnatal oral Mn exposure causes lasting attentional and impulse control deficits in adulthood, and whether continued lifelong Mn exposure exacerbates these effects, using a rat model of environmental Mn exposure.

          Methods:

          Neonates were exposed orally to 0, 25 or 50 mg Mn/kg/day during early postnatal life (PND 1–21) or throughout life from PND 1 until the end of the study. In adulthood, the animals were tested on a series of learning and attention tasks using the five-choice serial reaction time task.

          Results:

          Early postnatal Mn exposure caused lasting attentional dysfunction due to impairments in attentional preparedness, selective attention, and arousal regulation, whereas associative ability (learning) and impulse control were spared. The presence and severity of these deficits varied with the dose and duration of Mn exposure.

          Conclusions:

          This study is the first to show that developmental Mn exposure can cause lasting impairments in focused and selective attention and arousal regulation, and to identify the specific nature of the impairments. Given the importance of attention and arousal regulation in cognitive functioning, these findings substantiate concerns about the adverse effects of developmental Mn exposure in humans.

          Citation:

          Beaudin SA, Strupp BJ, Strawderman M, Smith DR. 2017. Early postnatal manganese exposure causes lasting impairment of selective and focused attention and arousal regulation in adult rats. Environ Health Perspect 125:230–237; http://dx.doi.org/10.1289/EHP258

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          Most cited references29

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          The 5-choice serial reaction time task: behavioural pharmacology and functional neurochemistry.

          The developmental history and application of the 5-choice serial reaction time task (5CSRTT) for measuring effects of drugs and other manipulations on attentional performance (and stimulus control) in rats is reviewed. The 5CSRTT has been used for measuring effects of systemic drug treatments and also central manipulations such as neurochemical lesions on various aspects of attentional control, including sustained, selective and divided attention--and is relevant to the definition of neural systems of attention and applications to human disorders such as attention deficit/hyperactivity disorder (ADHD) and Alzheimer's disease. The 5CSRTT is implemented in a specially designed operant chamber with multiple response locations ('nine-hole box') using food reinforcers to maintain performance on baseline sessions (about 100 trials) at criterion levels of accuracy and trials completed. The 5CSRTT can be used for measuring various aspects of attentional control over performance with its main measures of accuracy, premature responding, correct response latencies and latency to collect earned food pellets. The data reviewed include studies mainly of systemic and intra-cerebral effects of adrenoceptor, dopamine receptor, serotoninergic receptor and cholinergic receptor agents. These are compared with investigations of effects of selective chemical neurotoxins and excitotoxins applied to discrete parts of the forebrain, in order to define the neural and neurochemical substrates of attentional function. Furthermore, these results are integrated with findings from in vivo microdialysis in freely moving rats or metabolic studies. The monoaminergic and cholinergic systems appear to play separable roles in different aspects of performance controlled by the 5CSRTT, in neural systems centred on the prefrontal cortex, cingulate cortex and striatum. These conclusions are considered in the methodological and theoretical context of other psychopharmacological studies of attention in animals and humans.
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            The application of the 5-choice serial reaction time task for the assessment of visual attentional processes and impulse control in rats.

            One popular way of measuring visual attentional processes in the rat is using 5-choice serial reaction time task (5-CSRTT). This paradigm requires subjects to detect brief flashes of light presented in a pseudorandom order in one of five spatial locations over a large number of trials. For this task, the animals are trained for approximately 30-40 daily sessions during which they gradually learn to respond in the appropriate aperture within a certain amount of time. If they fail to respond, respond in the wrong hole or at an inappropriate time, a short period of darkness (time-out) is presented as punishment and no reward is delivered. The 5-CSRTT provides the possibility to test the effects of various neural, pharmacological and behavioral manipulations on discrete and somewhat independent measures of behavioral control, including accuracy of discrimination, impulsivity, perseverative responses and response latencies.
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              Intellectual Impairment in School-Age Children Exposed to Manganese from Drinking Water

              Background Manganese is an essential nutrient, but in excess it can be a potent neurotoxicant. Despite the common occurrence of manganese in groundwater, the risks associated with this source of exposure are largely unknown. Objectives Our first aim was to assess the relations between exposure to manganese from drinking water and children’s intelligence quotient (IQ). Second, we examined the relations between manganese exposures from water consumption and from the diet with children’s hair manganese concentration. Methods This cross-sectional study included 362 children 6–13 years of age living in communities supplied by groundwater. Manganese concentration was measured in home tap water (MnW) and children’s hair (MnH). We estimated manganese intake from water ingestion and the diet using a food frequency questionnaire and assessed IQ with the Wechsler Abbreviated Scale of Intelligence. Results The median MnW in children’s home tap water was 34 μg/L (range, 1–2,700 μg/L). MnH increased with manganese intake from water consumption, but not with dietary manganese intake. Higher MnW and MnH were significantly associated with lower IQ scores. A 10-fold increase in MnW was associated with a decrease of 2.4 IQ points (95% confidence interval: −3.9 to −0.9; p < 0.01), adjusting for maternal intelligence, family income, and other potential confounders. There was a 6.2-point difference in IQ between children in the lowest and highest MnW quintiles. MnW was more strongly associated with Performance IQ than Verbal IQ. Conclusions The findings of this cross-sectional study suggest that exposure to manganese at levels common in groundwater is associated with intellectual impairment in children.
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                Author and article information

                Journal
                Environ Health Perspect
                Environ. Health Perspect
                EHP
                Environmental Health Perspectives
                National Institute of Environmental Health Sciences
                0091-6765
                1552-9924
                6 July 2016
                February 2017
                : 125
                : 2
                : 230-237
                Affiliations
                [1 ]Department of Microbiology and Environmental Toxicology, University of California, Santa Cruz, Santa Cruz, California, USA
                [2 ]Division of Nutritional Sciences, and
                [3 ]Department of Psychology, Cornell University, Ithaca, New York, USA
                Author notes
                []Address correspondence to D.R. Smith, Department of Microbiology and Environmental Toxicology, University of California, Santa Cruz, 1156 High St., Santa Cruz, CA 95064 USA. Telephone: (831) 459-5041. E-mail: drsmith@ 123456ucsc.edu
                Article
                EHP258
                10.1289/EHP258
                5289906
                27384154
                7c4dd1fc-a215-4811-b2e4-d7882a26c9b8

                Publication of EHP lies in the public domain and is therefore without copyright. All text from EHP may be reprinted freely. Use of materials published in EHP should be acknowledged (for example, “Reproduced with permission from Environmental Health Perspectives”); pertinent reference information should be provided for the article from which the material was reproduced. Articles from EHP, especially the News section, may contain photographs or illustrations copyrighted by other commercial organizations or individuals that may not be used without obtaining prior approval from the holder of the copyright.

                History
                : 17 December 2015
                : 28 March 2016
                : 7 June 2016
                Categories
                Research

                Public health
                Public health

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