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      The stressed brain of humans and rodents

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          Abstract

          After stress, the brain is exposed to waves of stress mediators, including corticosterone (in rodents) and cortisol (in humans). Corticosteroid hormones affect neuronal physiology in two time‐domains: rapid, non‐genomic actions primarily via mineralocorticoid receptors; and delayed genomic effects via glucocorticoid receptors. In parallel, cognitive processing is affected by stress hormones. Directly after stress, emotional behaviour involving the amygdala is strongly facilitated with cognitively a strong emphasis on the “now” and “self,” at the cost of higher cognitive processing. This enables the organism to quickly and adequately respond to the situation at hand. Several hours later, emotional circuits are dampened while functions related to the prefrontal cortex and hippocampus are promoted. This allows the individual to rationalize the stressful event and place it in the right context, which is beneficial in the long run. The brain's response to stress depends on an individual's genetic background in interaction with life events. Studies in rodents point to the possibility to prevent or reverse long‐term consequences of early life adversity on cognitive processing, by normalizing the balance between the two receptor types for corticosteroid hormones at a critical moment just before the onset of puberty.

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          Most cited references31

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          Dynamic adaptation of large-scale brain networks in response to acute stressors.

          Stress initiates an intricate response that affects diverse cognitive and affective domains, with the goal of improving survival chances in the light of changing environmental challenges. Here, we bridge animal data at cellular and systems levels with human work on brain-wide networks to propose a framework describing how stress-related neuromodulators trigger dynamic shifts in network balance, enabling an organism to comprehensively reallocate its neural resources according to cognitive demands. We argue that exposure to acute stress prompts a reallocation of resources to a salience network, promoting fear and vigilance, at the cost of an executive control network. After stress subsides, resource allocation to these two networks reverses, which normalizes emotional reactivity and enhances higher-order cognitive processes important for long-term survival. Copyright © 2014 Elsevier Ltd. All rights reserved.
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            Chronic early life stress induced by limited bedding and nesting (LBN) material in rodents: critical considerations of methodology, outcomes and translational potential

            The immediate and long term effects of exposure to early life stress (ELS) have been documented in humans and animal models. Even relatively brief periods of stress during the first 10 days of life in rodents can impact later behavioral regulation and the vulnerability to develop adult pathologies, in particular an impairment of cognitive functions and neurogenesis, but also modified social, emotional and conditioned fear responses. The development of preclinical models of ELS exposure allows the examination of mechanisms and testing of therapeutic approaches that are not possible in humans. Here we describe limited bedding and nesting (LBN) procedures, with models that produce altered maternal behavior ranging from fragmentation of care to maltreatment of infants. The purpose of this paper is to discuss important issues related to the implementation of this chronic ELS procedure and to describe some of the most prominent endpoints and consequences, focusing on areas of convergence between laboratories. Effects on the hypothalamic-pituitary adrenal (HPA) axis, gut axis and metabolism are presented in addition to changes in cognitive and emotional functions. Interestingly, recent data have suggested a strong sex difference in some of the reported consequences of the LBN paradigm, with females being more resilient in general than males. As both the chronic and intermittent variants of the LBN procedure have profound consequences on the offspring with minimal external intervention from the investigator, this model is advantageous ecologically and has a large translational potential. In addition to the direct effect of ELS on neurodevelopmental outcomes, exposure to adverse early environments can also have intergenerational impacts on mental health and function in subsequent generation offspring. Thus, advancing our understanding of the effect of ELS on brain and behavioral development is of critical concern for the health and wellbeing of both the current population, and for generations to come.
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              Nongenomic glucocorticoid inhibition via endocannabinoid release in the hypothalamus: a fast feedback mechanism.

              Glucocorticoid negative feedback in the brain controls stress, feeding, and neural-immune interactions by regulating the hypothalamic-pituitary-adrenal axis, but the mechanisms of inhibition of hypothalamic neurosecretory cells have never been elucidated. Using whole-cell patch-clamp recordings in an acute hypothalamic slice preparation, we demonstrate a rapid suppression of excitatory glutamatergic synaptic inputs to parvocellular neurosecretory neurons of the hypothalamic paraventricular nucleus (PVN) by the glucocorticoids dexamethasone and corticosterone. The effect was maintained with dexamethasone conjugated to bovine serum albumin and was not seen with direct intracellular glucocorticoid perfusion via the patch pipette, suggesting actions at a membrane receptor. The presynaptic inhibition of glutamate release by glucocorticoids was blocked by postsynaptic inhibition of G-protein activity with intracellular GDP-beta-S application, implicating a postsynaptic G-protein-coupled receptor and the release of a retrograde messenger. The glucocorticoid effect was not blocked by the nitric oxide synthesis antagonist N(G)-nitro-L-arginine methyl ester hydrochloride or by hemoglobin but was blocked completely by the CB1 cannabinoid receptor antagonists AM251 [N-(piperidin-1-yl)-5-(4-iodophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide] and AM281 [1-(2,4-dichlorophenyl)-5-(4-iodophenyl)-4-methyl-N-4-morpholinyl-1H-pyrazole-3-carboxamide] and mimicked and occluded by the cannabinoid receptor agonist WIN55,212-2 [(beta)-(+)-[2,3-dihydro-5-methyl-3-(4-morpholinylmethyl)pyrrolo[1,2,3-de]-1,4-benzoxazin-6-yl]-1-naphthalenylmethanone mesylate], indicating that it was mediated by retrograde endocannabinoid release. Several peptidergic subtypes of parvocellular neuron, identified by single-cell reverse transcripton-PCR analysis, were subject to rapid inhibitory glucocorticoid regulation, including corticotropin-releasing hormone-, thyrotropin-releasing hormone-, vasopressin-, and oxytocin-expressing neurons. Therefore, our findings reveal a mechanism of rapid glucocorticoid feedback inhibition of hypothalamic hormone secretion via endocannabinoid release in the PVN and provide a link between the actions of glucocorticoids and cannabinoids in the hypothalamus that regulate stress and energy homeostasis.
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                Author and article information

                Contributors
                m.joels-2@umcutrecht.nl
                Journal
                Acta Physiol (Oxf)
                Acta Physiol (Oxf)
                10.1111/(ISSN)1748-1716
                APHA
                Acta Physiologica (Oxford, England)
                John Wiley and Sons Inc. (Hoboken )
                1748-1708
                1748-1716
                16 April 2018
                June 2018
                : 223
                : 2 ( doiID: 10.1111/apha.2018.223.issue-2 )
                : e13066
                Affiliations
                [ 1 ] Department of Translational Neuroscience Brain Center Rudolf Magnus University Medical Center Utrecht Utrecht University Utrecht The Netherlands
                [ 2 ] University Medical Center Groningen University of Groningen Groningen The Netherlands
                Author notes
                [*] [* ] Correspondence

                M. Joëls, Department of Translational Neuroscience, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.

                Email: m.joels-2@ 123456umcutrecht.nl

                Author information
                http://orcid.org/0000-0002-4826-6209
                Article
                APHA13066
                10.1111/apha.13066
                5969253
                29575542
                23f8a96f-8682-446b-a9df-96932efc1d39
                © 2018 The Authors. Acta Physiologica published by John Wiley & Sons Ltd on behalf of Scandinavian Physiological Society

                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
                : 21 January 2018
                : 16 March 2018
                : 18 March 2018
                Page count
                Figures: 6, Tables: 0, Pages: 10, Words: 6129
                Funding
                Funded by: Consortium on Individual Development (CID), which is funded through the Gravitation program of the Dutch Ministry of Education, Culture, and Science and the Netherlands Organization for Scientific Research
                Award ID: 024.001.003
                Funded by: ZonMw (Top grant)
                Award ID: 91213017
                Funded by: Netherlands Organization for Scientific Research NWO (Veni grant)
                Award ID: 863.13.021
                Categories
                Review
                Review
                Custom metadata
                2.0
                apha13066
                June 2018
                Converter:WILEY_ML3GV2_TO_NLMPMC version:version=5.3.8.2 mode:remove_FC converted:25.05.2018

                Anatomy & Physiology
                amygdala,corticosterone,cortisol,early life stress,hippocampus
                Anatomy & Physiology
                amygdala, corticosterone, cortisol, early life stress, hippocampus

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