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      The Role of Dietary Polyphenols on Adult Hippocampal Neurogenesis: Molecular Mechanisms and Behavioural Effects on Depression and Anxiety

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          Abstract

          Although it has been long believed that new neurons were only generated during development, there is now growing evidence indicating that at least two regions in the brain are capable of continuously generating functional neurons: the subventricular zone and the dentate gyrus of the hippocampus. Adult hippocampal neurogenesis (AHN) is a widely observed phenomenon verified in different adult mammalian species including humans. Factors such as environmental enrichment, voluntary exercise, and diet have been linked to increased levels of AHN. Conversely, aging, stress, anxiety and depression have been suggested to hinder it. However, the mechanisms underlying these effects are still unclear and yet to be determined. In this paper, we discuss some recent findings addressing the effects of different dietary polyphenols on hippocampal cell proliferation and differentiation, models of anxiety, and depression as well as some proposed molecular mechanisms underlying those effects with particular focus on those related to AHN. As a whole, dietary polyphenols seem to exert positive effects on anxiety and depression, possibly in part via regulation of AHN. Studies on the effects of dietary polyphenols on behaviour and AHN may play an important role in the approach to use diet as part of the therapeutic interventions for mental-health-related conditions.

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          Mechanisms and functional implications of adult neurogenesis.

          The generation of new neurons is sustained throughout adulthood in the mammalian brain due to the proliferation and differentiation of adult neural stem cells. In this review, we discuss the factors that regulate proliferation and fate determination of adult neural stem cells and describe recent studies concerning the integration of newborn neurons into the existing neural circuitry. We further address the potential significance of adult neurogenesis in memory, depression, and neurodegenerative disorders such as Alzheimer's and Parkinson's disease.
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            More hippocampal neurons in adult mice living in an enriched environment.

            Neurogenesis occurs in the dentate gyrus of the hippocampus throughout the life of a rodent, but the function of these new neurons and the mechanisms that regulate their birth are unknown. Here we show that significantly more new neurons exist in the dentate gyrus of mice exposed to an enriched environment compared with littermates housed in standard cages. We also show, using unbiased stereology, that the enriched mice have a larger hippocampal granule cell layer and 15 per cent more granule cell neurons in the dentate gyrus.
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              Adult hippocampal neurogenesis buffers stress responses and depressive behavior

              Summary Glucocorticoids are released in response to stressful experiences and serve many beneficial homeostatic functions. However, dysregulation of glucocorticoids is associated with cognitive impairments and depressive illness 1, 2 . In the hippocampus, a brain region densely populated with receptors for stress hormones, stress and glucocorticoids strongly inhibit adult neurogenesis 3 . Decreased neurogenesis has been implicated in the pathogenesis of anxiety and depression, but direct evidence for this role is lacking 4, 5 . Here we show that adult-born hippocampal neurons are required for normal expression of the endocrine and behavioral components of the stress response. Using transgenic and radiation methods to specifically inhibit adult neurogenesis, we find that glucocorticoid levels are slower to recover after moderate stress and are less suppressed by dexamethasone in neurogenesis-deficient mice compared with intact mice, consistent with a role for the hippocampus in regulation of the hypothalamic-pituitary-adrenal (HPA) axis 6, 7 . Relative to controls, neurogenesis-deficient mice showed increased food avoidance in a novel environment after acute stress, increased behavioral despair in the forced swim test, and decreased sucrose preference, a measure of anhedonia. These findings identify a small subset of neurons within the dentate gyrus that are critical for hippocampal negative control of the HPA axis and support a direct role for adult neurogenesis in depressive illness.
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                Author and article information

                Journal
                Oxid Med Cell Longev
                Oxid Med Cell Longev
                OXIMED
                Oxidative Medicine and Cellular Longevity
                Hindawi Publishing Corporation
                1942-0900
                1942-0994
                2012
                28 June 2012
                : 2012
                : 541971
                Affiliations
                1Institute of Psychiatry, King's College London, 125 Coldharbour Lane, London SE5 9NU, UK
                2Program of Neurobiology, Laboratory of Neurobiology of the Retina, Institute of Biophysics, Universidade Federal do Rio de Janeiro (UFRJ), Bloco C, sala 31, Avenida Carlos Chagas Filho 373, 21941-902 Rio de Janeiro, RJ, Brazil
                3Laboratory of Panic & Respiration, Institute of Psychiatry, Universidade Federal do Rio de Janeiro (UFRJ), Avenida Venceslau Brás, 71 Fundos, 22290-140 Rio de Janeiro, RJ, Brazil
                Author notes

                Academic Editor: Tullia Maraldi

                Article
                10.1155/2012/541971
                3395274
                22829957
                5d77bb9f-cb29-4654-a33a-600eb9313d67
                Copyright © 2012 Gisele Pereira Dias 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
                : 10 February 2012
                : 10 April 2012
                : 17 April 2012
                Categories
                Review Article

                Molecular medicine
                Molecular medicine

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