Importance of the brain corticosteroid receptor balance in metaplasticity, cognitive performance and neuro-inflammation

•Resilience depends on balanced MR- and GR-mediated actions.•Brain MR promotes appraisal processes, choice of coping style, learning and memory retrieval.•Brain GR promotes recovery, rational decisions and contextual memory.•Corticosterone-induced amygdala metaplasticity tunes emotional memory.•Tran...

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Published in:Frontiers in neuroendocrinology 2018-04, Vol.49, p.124-145
Main Authors: de Kloet, E.R., Meijer, O.C., de Nicola, A.F., de Rijk, R.H., Joëls, M.
Format: Article
Language:English
Subjects:
Amygdala
Amygdala - metabolism
Animals
Brain
Cognitive Dysfunction - etiology
Cognitive Dysfunction - metabolism
Cognitive Dysfunction - physiopathology
Coregulators
Cortisol
Glucocorticoid receptors
Hippocampus
Hippocampus - metabolism
Inflammation
Inflammation - metabolism
Memory
Metaplasticity
Mineralocorticoid receptors
NeuroD transcription factor
Neuronal Plasticity - physiology
Receptors, Glucocorticoid - metabolism
Receptors, Mineralocorticoid - metabolism
Stress
Stress, Psychological - complications
Stress, Psychological - metabolism
Stress, Psychological - physiopathology
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Summary:•Resilience depends on balanced MR- and GR-mediated actions.•Brain MR promotes appraisal processes, choice of coping style, learning and memory retrieval.•Brain GR promotes recovery, rational decisions and contextual memory.•Corticosterone-induced amygdala metaplasticity tunes emotional memory.•Transcription factor and coregulators confer specificity to MR- and GR-mediated actions. Bruce McEwen’s discovery of receptors for corticosterone in the rat hippocampus introduced higher brain circuits in the neuroendocrinology of stress. Subsequently, these receptors were identified as mineralocorticoid receptors (MRs) that are involved in appraisal processes, choice of coping style, encoding and retrieval. The MR-mediated actions on cognition are complemented by slower actions via glucocorticoid receptors (GRs) on contextualization, rationalization and memory storage of the experience. These sequential phases in cognitive performance depend on synaptic metaplasticity that is regulated by coordinate MR- and GR activation. The receptor activation includes recruitment of coregulators and transcription factors as determinants of context-dependent specificity in steroid action; they can be modulated by genetic variation and (early) experience. Interestingly, inflammatory responses to damage seem to be governed by a similarly balanced MR:GR-mediated action as the initiating, terminating and priming mechanisms involved in stress-adaptation. We conclude with five questions challenging the MR:GR balance hypothesis.
ISSN:0091-3022
1095-6808
DOI:10.1016/j.yfrne.2018.02.003