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      Exercise-Mediated Neurogenesis in the Hippocampus via BDNF

      review-article
      ,
      Frontiers in Neuroscience
      Frontiers Media S.A.
      neurotrophin, TrkB, subgranular zone, neuroprotective, dentate gyrus

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          Abstract

          Exercise is known to have numerous neuroprotective and cognitive benefits, especially pertaining to memory and learning related processes. One potential link connecting them is exercise-mediated hippocampal neurogenesis, in which new neurons are generated and incorporated into hippocampal circuits. The present review synthesizes the extant literature detailing the relationship between exercise and hippocampal neurogenesis, and identifies a key molecule mediating this process, brain-derived neurotrophic factor (BDNF). As a member of the neurotrophin family, BDNF regulates many of the processes within neurogenesis, such as differentiation and survival. Although much more is known about the direct role that exercise and BDNF have on hippocampal neurogenesis in rodents, their corresponding cognitive benefits in humans will also be discussed. Specifically, what is known about exercise-mediated hippocampal neurogenesis will be presented as it relates to BDNF to highlight the critical role that it plays. Due to the inaccessibility of the human brain, much less is known about the role BDNF plays in human hippocampal neurogenesis. Limitations and future areas of research with regards to human neurogenesis will thus be discussed, including indirect measures of neurogenesis and single nucleotide polymorphisms within the BDNF gene.

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          Most cited references54

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          Exercise induces hippocampal BDNF through a PGC-1α/FNDC5 pathway.

          Exercise can improve cognitive function and has been linked to the increased expression of brain-derived neurotrophic factor (BDNF). However, the underlying molecular mechanisms driving the elevation of this neurotrophin remain unknown. Here we show that FNDC5, a previously identified muscle protein that is induced in exercise and is cleaved and secreted as irisin, is also elevated by endurance exercise in the hippocampus of mice. Neuronal Fndc5 gene expression is regulated by PGC-1α, and Pgc1a(-/-) mice show reduced Fndc5 expression in the brain. Forced expression of FNDC5 in primary cortical neurons increases Bdnf expression, whereas RNAi-mediated knockdown of FNDC5 reduces Bdnf. Importantly, peripheral delivery of FNDC5 to the liver via adenoviral vectors, resulting in elevated blood irisin, induces expression of Bdnf and other neuroprotective genes in the hippocampus. Taken together, our findings link endurance exercise and the important metabolic mediators, PGC-1α and FNDC5, with BDNF expression in the brain. Copyright © 2013 Elsevier Inc. All rights reserved.
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            The role of exercise and PGC1alpha in inflammation and chronic disease.

            Inadequate physical activity is linked to many chronic diseases. But the mechanisms that tie muscle activity to health are unclear. The transcriptional coactivator PGC1alpha has recently been shown to regulate several exercise-associated aspects of muscle function. We propose that this protein controls muscle plasticity, suppresses a broad inflammatory response and mediates the beneficial effects of exercise.
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              Astrocytes give rise to new neurons in the adult mammalian hippocampus.

              Neurogenesis in the dentate gyrus of the hippocampus persists throughout life in many vertebrates, including humans. The progenitors of these new neurons reside in the subgranular layer (SGL) of the dentate gyrus. Although stem cells that can self-renew and generate new neurons and glia have been cultured from the adult mammalian hippocampus, the in vivo primary precursors for the formation of new neurons have not been identified. Here we show that SGL cells, which express glial fibrillary acidic protein and have the characteristics of astrocytes, divide and generate new neurons under normal conditions or after the chemical removal of actively dividing cells. We also describe a population of small electron-dense SGL cells, which we call type D cells and are derived from the astrocytes and probably function as a transient precursor in the formation of new neurons. These results reveal the origins of new neurons in the adult hippocampus.
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                Author and article information

                Contributors
                Journal
                Front Neurosci
                Front Neurosci
                Front. Neurosci.
                Frontiers in Neuroscience
                Frontiers Media S.A.
                1662-4548
                1662-453X
                07 February 2018
                2018
                : 12
                : 52
                Affiliations
                Department of Psychology, Northwestern University , Evanston, IL, United States
                Author notes

                Edited by: Vincent Tropepe, University of Toronto, Canada

                Reviewed by: Matteo Bergami, Cologne Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases, Germany; Carmen Vivar, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional (CINVESTAV-IPN), Mexico

                *Correspondence: Patrick Z. Liu patrick.liu@ 123456northwestern.edu

                This article was submitted to Neurogenesis, a section of the journal Frontiers in Neuroscience

                Article
                10.3389/fnins.2018.00052
                5808288
                29467613
                120a2d5d-516a-46b7-84bb-fb6efd618faf
                Copyright © 2018 Liu and Nusslock.

                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
                : 19 November 2017
                : 23 January 2018
                Page count
                Figures: 0, Tables: 0, Equations: 0, References: 75, Pages: 6, Words: 5585
                Categories
                Neuroscience
                Mini Review

                Neurosciences
                neurotrophin,trkb,subgranular zone,neuroprotective,dentate gyrus
                Neurosciences
                neurotrophin, trkb, subgranular zone, neuroprotective, dentate gyrus

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