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      Bridging the Gap between Brain-Derived Neurotrophic Factor and Glucocorticoid Effects on Brain Networks

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          Abstract

          Behavioral choices made by the brain during stress depend on glucocorticoid and brain-derived neurotrophic factor (BDNF) signaling pathways acting in synchrony in the mesolimbic (reward) and corticolimbic (emotion) neural networks. Deregulated expression of BDNF and glucocorticoid receptors in brain valuation areas may compromise the integration of signals. Glucocorticoid receptor phosphorylation upon BDNF signaling in neurons represents one mechanism underlying the integration of BDNF and glucocorticoid signals that when off balance may lay the foundation of maladaptations to stress. Here, we propose that BDNF signaling conditions glucocorticoid responses impacting neural plasticity in the mesocorticolimbic system. This provides a novel molecular framework for understanding how brain networks use BDNF and glucocorticoid signaling contingencies to forge receptive neuronal fields in temporal domains defined by behavioral experience, and in mood disorders.

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          Most cited references66

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          A neurotrophic model for stress-related mood disorders.

          There is a growing body of evidence demonstrating that stress decreases the expression of brain-derived neurotrophic factor (BDNF) in limbic structures that control mood and that antidepressant treatment reverses or blocks the effects of stress. Decreased levels of BDNF, as well as other neurotrophic factors, could contribute to the atrophy of certain limbic structures, including the hippocampus and prefrontal cortex that has been observed in depressed subjects. Conversely, the neurotrophic actions of antidepressants could reverse neuronal atrophy and cell loss and thereby contribute to the therapeutic actions of these treatments. This review provides a critical examination of the neurotrophic hypothesis of depression that has evolved from this work, including analysis of preclinical cellular (adult neurogenesis) and behavioral models of depression and antidepressant actions, as well as clinical neuroimaging and postmortem studies. Although there are some limitations, the results of these studies are consistent with the hypothesis that decreased expression of BDNF and possibly other growth factors contributes to depression and that upregulation of BDNF plays a role in the actions of antidepressant treatment.
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            Essential role of BDNF in the mesolimbic dopamine pathway in social defeat stress.

            Mice experiencing repeated aggression develop a long-lasting aversion to social contact, which can be normalized by chronic, but not acute, administration of antidepressant. Using viral-mediated, mesolimbic dopamine pathway-specific knockdown of brain-derived neurotrophic factor (BDNF), we showed that BDNF is required for the development of this experience-dependent social aversion. Gene profiling in the nucleus accumbens indicates that local knockdown of BDNF obliterates most of the effects of repeated aggression on gene expression within this circuit, with similar effects being produced by chronic treatment with antidepressant. These results establish an essential role for BDNF in mediating long-term neural and behavioral plasticity in response to aversive social experiences.
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              The BDNF val66met Polymorphism Affects Activity-Dependent Secretion of BDNF and Human Memory and Hippocampal Function

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                Author and article information

                Journal
                NEN
                Neuroendocrinology
                10.1159/issn.0028-3835
                Neuroendocrinology
                S. Karger AG
                978-3-318-06640-1
                978-3-318-06641-8
                0028-3835
                1423-0194
                2019
                September 2019
                20 December 2018
                : 109
                : 3
                : 277-284
                Affiliations
                [_a] aInstitut de Genomique Fonctionnelle, Inserm, CNRS, University of Montpellier, Montpellier, France
                [_b] bSkirball Institute of Biomolecular Medicine, New York University Langone Medical Center, New York, New York, USA
                [_c] cNew York University Langone Medical Center, New York, New York, USA
                Author notes
                *Freddy Jeanneteau, Institut de Genomique Fonctionnelle, Inserm, CNRS, University of Montpellier, FR–34090 Montpellier (France), E-Mail freddy.jeanneteau@igf.cnrs.fr
                Author information
                https://orcid.org/0000-0002-9606-2892
                Article
                496392 Neuroendocrinology 2019;109:277–284
                10.1159/000496392
                30572337
                3e358cb7-40ed-40e5-9b94-e3053a1bbce4
                © 2018 S. Karger AG, Basel

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                History
                : 12 October 2018
                : 19 December 2018
                Page count
                Figures: 3, Pages: 8
                Categories
                At the Cutting Edge

                Endocrinology & Diabetes,Neurology,Nutrition & Dietetics,Sexual medicine,Internal medicine,Pharmacology & Pharmaceutical medicine
                Connectivity,Depression,Action control,Salience network,Stress

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