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      Depressive-Like Behaviors Induced by Chronic Social Defeat Stress Are Associated With HDAC7 Reduction in the Nucleus Accumbens

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          Abstract

          Persistent symptoms of depression indicate the adaptive involvement of stable molecules in the brain that may be manifested at the level of chromatin remodeling, such as histone acetylation. Former studies have identified alterations in histone acetylation and deacetylation in several animal models about depression. However, the specific histone deacetylases related with depression are needed to be explored. Here, social avoidance behaviors, anxiety-, and depression-like behaviors were all found in mice suffered from chronic social defeat stress. Moreover, we also discovered that the amount of the class II histone deacetylase, HDAC7 rather than HDAC2, was significantly decreased in the nucleus accumbens of defeated mice, which suggested that HDAC7 might be a crucial histone deacetylase in a chronic social defeat stress model. Our data showed that the depressive-like behaviors induced by chronic social defeat stress were associated with HDAC7 reduction in nucleus accumbens. HDAC7 might be a promising therapeutic target for depression.

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          Most cited references34

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          Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method.

          The two most commonly used methods to analyze data from real-time, quantitative PCR experiments are absolute quantification and relative quantification. Absolute quantification determines the input copy number, usually by relating the PCR signal to a standard curve. Relative quantification relates the PCR signal of the target transcript in a treatment group to that of another sample such as an untreated control. The 2(-Delta Delta C(T)) method is a convenient way to analyze the relative changes in gene expression from real-time quantitative PCR experiments. The purpose of this report is to present the derivation, assumptions, and applications of the 2(-Delta Delta C(T)) method. In addition, we present the derivation and applications of two variations of the 2(-Delta Delta C(T)) method that may be useful in the analysis of real-time, quantitative PCR data. Copyright 2001 Elsevier Science (USA).
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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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              Molecular adaptations underlying susceptibility and resistance to social defeat in brain reward regions.

              While stressful life events are an important cause of psychopathology, most individuals exposed to adversity maintain normal psychological functioning. The molecular mechanisms underlying such resilience are poorly understood. Here, we demonstrate that an inbred population of mice subjected to social defeat can be separated into susceptible and unsusceptible subpopulations that differ along several behavioral and physiological domains. By a combination of molecular and electrophysiological techniques, we identify signature adaptations within the mesolimbic dopamine circuit that are uniquely associated with vulnerability or insusceptibility. We show that molecular recapitulations of three prototypical adaptations associated with the unsusceptible phenotype are each sufficient to promote resistant behavior. Our results validate a multidisciplinary approach to examine the neurobiological mechanisms of variations in stress resistance, and illustrate the importance of plasticity within the brain's reward circuits in actively maintaining an emotional homeostasis.
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                Author and article information

                Contributors
                Journal
                Front Psychiatry
                Front Psychiatry
                Front. Psychiatry
                Frontiers in Psychiatry
                Frontiers Media S.A.
                1664-0640
                26 January 2021
                2020
                : 11
                : 586904
                Affiliations
                [1] 1Imaging Department, Kaifeng Central Hospital , Kaifeng, China
                [2] 2Department of Clinical Laboratory, The Second Hospital, Cheeloo College of Medicine, Shandong University , Jinan, China
                [3] 3Key Laboratory of Brain Functional Remodeling, Department of Neurosurgery, Qilu Hospital of Shandong University and Brain Science Research Institute, Shandong University , Jinan, China
                [4] 4Department of Obstetrics, The Second Hospital of Shandong University , Jinan, China
                Author notes

                Edited by: Karim Abdel Aziz, United Arab Emirates University, United Arab Emirates

                Reviewed by: Aislinn Joanmarie Williams, The University of Iowa, United States; Herb E. Covington, Tufts University, United States

                *Correspondence: Xu Jing jingxu1990@ 123456126.com

                This article was submitted to Mood and Anxiety Disorders, a section of the journal Frontiers in Psychiatry

                †These authors have contributed equally to this work

                Article
                10.3389/fpsyt.2020.586904
                7870706
                33574772
                10fcf6f5-48d5-455d-b653-0f4767df17ef
                Copyright © 2021 Qian, Yu, Wang, Niu, Shi, Cheng, Xu, Jin and Jing.

                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(s) 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
                : 24 July 2020
                : 29 December 2020
                Page count
                Figures: 5, Tables: 0, Equations: 0, References: 34, Pages: 8, Words: 5353
                Categories
                Psychiatry
                Original Research

                Clinical Psychology & Psychiatry
                chronic social defeat stress,depression,hdac7,nucleus accumbens (nac),epigenetic

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