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      The involvement of astrocytes in early‐life adversity induced programming of the brain

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          Abstract

          Early‐life adversity (ELA) in the form of stress, inflammation, or malnutrition, can increase the risk of developing psychopathology or cognitive problems in adulthood. The neurobiological substrates underlying this process remain unclear. While neuronal dysfunction and microglial contribution have been studied in this context, only recently the role of astrocytes in early‐life programming of the brain has been appreciated. Astrocytes serve many basic roles for brain functioning (e.g., synaptogenesis, glutamate recycling), and are unique in their capacity of sensing and integrating environmental signals, as they are the first cells to encounter signals from the blood, including hormonal changes (e.g., glucocorticoids), immune signals, and nutritional information. Integration of these signals is especially important during early development, and therefore we propose that astrocytes contribute to ELA induced changes in the brain by sensing and integrating environmental signals and by modulating neuronal development and function. Studies in rodents have already shown that ELA can impact astrocytes on the short and long term, however, a critical review of these results is currently lacking. Here, we will discuss the developmental trajectory of astrocytes, their ability to integrate stress, immune, and nutritional signals from the early environment, and we will review how different types of early adversity impact astrocytes.

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          Most cited references184

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          Brain energy metabolism: focus on astrocyte-neuron metabolic cooperation.

          The energy requirements of the brain are very high, and tight regulatory mechanisms operate to ensure adequate spatial and temporal delivery of energy substrates in register with neuronal activity. Astrocytes-a type of glial cell-have emerged as active players in brain energy delivery, production, utilization, and storage. Our understanding of neuroenergetics is rapidly evolving from a "neurocentric" view to a more integrated picture involving an intense cooperativity between astrocytes and neurons. This review focuses on the cellular aspects of brain energy metabolism, with a particular emphasis on the metabolic interactions between neurons and astrocytes. Copyright © 2011 Elsevier Inc. All rights reserved.
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            Thrombospondins are astrocyte-secreted proteins that promote CNS synaptogenesis.

            The establishment of neural circuitry requires vast numbers of synapses to be generated during a specific window of brain development, but it is not known why the developing mammalian brain has a much greater capacity to generate new synapses than the adult brain. Here we report that immature but not mature astrocytes express thrombospondins (TSPs)-1 and -2 and that these TSPs promote CNS synaptogenesis in vitro and in vivo. TSPs induce ultrastructurally normal synapses that are presynaptically active but postsynaptically silent and work in concert with other, as yet unidentified, astrocyte-derived signals to produce functional synapses. These studies identify TSPs as CNS synaptogenic proteins, provide evidence that astrocytes are important contributors to synaptogenesis within the developing CNS, and suggest that TSP-1 and -2 act as a permissive switch that times CNS synaptogenesis by enabling neuronal molecules to assemble into synapses within a specific window of CNS development.
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              Tripartite synapses: glia, the unacknowledged partner.

              According to the classical view of the nervous system, the numerically superior glial cells have inferior roles in that they provide an ideal environment for neuronal-cell function. However, there is a wave of new information suggesting that glia are intimately involved in the active control of neuronal activity and synaptic neurotransmission. Recent evidence shows that glia respond to neuronal activity with an elevation of their internal Ca2+ concentration, which triggers the release of chemical transmitters from glia themselves and, in turn, causes feedback regulation of neuronal activity and synaptic strength. In view of these new insights, this article suggests that perisynaptic Schwann cells and synaptically associated astrocytes should be viewed as integral modulatory elements of tripartite synapses.
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                Author and article information

                Contributors
                a.korosi@uva.nl
                Journal
                Glia
                Glia
                10.1002/(ISSN)1098-1136
                GLIA
                Glia
                John Wiley & Sons, Inc. (Hoboken, USA )
                0894-1491
                1098-1136
                30 April 2019
                September 2019
                : 67
                : 9 ( doiID: 10.1002/glia.v67.9 )
                : 1637-1653
                Affiliations
                [ 1 ] Center for Neuroscience, Swammerdam Institute for Life Sciences, University of Amsterdam Amsterdam The Netherlands
                [ 2 ] Department of Molecular and Cellular Neurobiology, Center for Neurogenomics and Cognitive Research Amsterdam Neuroscience, Vrije Universiteit Amsterdam The Netherlands
                [ 3 ] Complex Trait Genetics, Center for Neurogenomics and Cognitive Research Amsterdam Neuroscience, Vrije Universiteit Amsterdam The Netherlands
                Author notes
                [*] [* ] Correspondence

                Aniko Korosi, Center for Neuroscience, Swammerdam Institute for Life Sciences, University of Amsterdam, Science Park 904, 1098 XH Amsterdam, The Netherlands.

                Email: a.korosi@ 123456uva.nl

                Author information
                https://orcid.org/0000-0003-4416-3875
                https://orcid.org/0000-0002-3739-3755
                https://orcid.org/0000-0001-9701-3331
                Article
                GLIA23625
                10.1002/glia.23625
                6767561
                31038797
                a8ddbf8a-7720-4bc3-a04e-34ee026ed161
                © 2019 The Authors. Glia published by Wiley Periodicals, Inc.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                : 04 February 2019
                : 29 March 2019
                : 29 March 2019
                Page count
                Figures: 1, Tables: 0, Pages: 17, Words: 19540
                Funding
                Funded by: Amsterdam Brain Mind Project (ABMP)
                Funded by: Meervoud NWO
                Categories
                Review Article
                Review Articles
                Custom metadata
                2.0
                glia23625
                September 2019
                Converter:WILEY_ML3GV2_TO_NLMPMC version:5.6.9 mode:remove_FC converted:30.09.2019

                Neurosciences
                early inflammation,early malnutrition,early stress,gfap,maternal separation/deprivation

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