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      Neurobiology of resilience.

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      Journal: Nature neuroscience
      Keywords: Animals, Brain, pathology, Dehydroepiandrosterone, metabolism, Disease Models, Animal, Early Growth Response Transcription Factors, Humans, Hypothalamo-Hypophyseal System, physiopathology, Neurobiology, Neuropeptide Y, Pituitary-Adrenal System, Resilience, Psychological, Stress, Psychological, genetics, psychology, Testosterone

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          Abstract

          Humans exhibit a remarkable degree of resilience in the face of extreme stress, with most resisting the development of neuropsychiatric disorders. Over the past 5 years, there has been increasing interest in the active, adaptive coping mechanisms of resilience; however, in humans, most published work focuses on correlative neuroendocrine markers that are associated with a resilient phenotype. In this review, we highlight a growing literature in rodents that is starting to complement the human work by identifying the active behavioral, neural, molecular and hormonal basis of resilience. The therapeutic implications of these findings are important and can pave the way for an innovative approach to drug development for a range of stress-related syndromes.

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          Ordinary magic. Resilience processes in development.

          A. S. Masten (2001)
          The study of resilience in development has overturned many negative assumptions and deficit-focused models about children growing up under the threat of disadvantage and adversity. The most surprising conclusion emerging from studies of these children is the ordinariness of resilience. An examination of converging findings from variable-focused and person-focused investigations of these phenomena suggests that resilience is common and that it usually arises from the normative functions of human adaptational systems, with the greatest threats to human development being those that compromise these protective systems. The conclusion that resilience is made of ordinary rather than extraordinary processes offers a more positive outlook on human development and adaptation, as well as direction for policy and practice aimed at enhancing the development of children at risk for problems and psychopathology.
          Article 0 comments Cited 705 times – based on 0 reviews     Review now
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            Essential role of BDNF in the mesolimbic dopamine pathway in social defeat stress.

            Olivier Berton, Colleen A. McClung, Ralph J Dileone … (2006)
            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.
            Article 0 comments Cited 543 times – based on 0 reviews     Review now
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              Sustained hippocampal chromatin regulation in a mouse model of depression and antidepressant action.

              Nadia Tsankova, Olivier Berton, William Renthal … (2006)
              To better understand the molecular mechanisms of depression and antidepressant action, we administered chronic social defeat stress followed by chronic imipramine (a tricyclic antidepressant) to mice and studied adaptations at the levels of gene expression and chromatin remodeling of five brain-derived neurotrophic factor (Bdnf) splice variant mRNAs (I-V) and their unique promoters in the hippocampus. Defeat stress induced lasting downregulation of Bdnf transcripts III and IV and robustly increased repressive histone methylation at their corresponding promoters. Chronic imipramine reversed this downregulation and increased histone acetylation at these promoters. This hyperacetylation by chronic imipramine was associated with a selective downregulation of histone deacetylase (Hdac) 5. Furthermore, viral-mediated HDAC5 overexpression in the hippocampus blocked imipramine's ability to reverse depression-like behavior. These experiments underscore an important role for histone remodeling in the pathophysiology and treatment of depression and highlight the therapeutic potential for histone methylation and deacetylation inhibitors in depression.
              Article 0 comments Cited 426 times – based on 0 reviews     Review now
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                Author and article information

                Journal
                PubMed ID:: 23064380
                PMC ID:: 3580862
                DOI:: 10.1038/nn.3234

                ScienceOpen disciplines: Chemistry
                Keywords: Animals,Brain,pathology,Dehydroepiandrosterone,metabolism,Disease Models, Animal,Early Growth Response Transcription Factors,Humans,Hypothalamo-Hypophyseal System,physiopathology,Neurobiology,Neuropeptide Y,Pituitary-Adrenal System,Resilience, Psychological,Stress, Psychological,genetics,psychology,Testosterone
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                ScienceOpen disciplines: Chemistry
                Keywords: Animals, Brain, pathology, Dehydroepiandrosterone, metabolism, Disease Models, Animal, Early Growth Response Transcription Factors, Humans, Hypothalamo-Hypophyseal System, physiopathology, Neurobiology, Neuropeptide Y, Pituitary-Adrenal System, Resilience, Psychological, Stress, Psychological, genetics, psychology, Testosterone

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