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

E. R. de Kloet*, O. C. Meijer, A. F. de Nicola, R. H. de Rijk, M. Joels

*Corresponding author for this work

    Research output: Contribution to journalReview articleAcademicpeer-review

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    Abstract

    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.

    Original languageEnglish
    Pages (from-to)124-145
    Number of pages22
    JournalFrontiers in Neuroendocrinology
    Volume49
    DOIs
    Publication statusPublished - Apr-2018

    Keywords

    • Stress
    • Brain
    • Memory
    • Inflammation
    • Hippocampus
    • Amygdala
    • Metaplasticity
    • Cortisol
    • Mineralocorticoid receptors
    • Glucocorticoid receptors
    • Coregulators
    • NeuroD transcription factor
    • PITUITARY-ADRENAL AXIS
    • SPONTANEOUSLY HYPERTENSIVE-RATS
    • CORTICOTROPIN-RELEASING HORMONE
    • MESSENGER-RNA EXPRESSION
    • BLOCKING GLUCOCORTICOID-RECEPTORS
    • STRESS-INDUCED ENHANCEMENT
    • MINERALOCORTICOID TYPE-I
    • HIPPOCAMPAL CA1 NEURONS
    • MULTIPLE MEMORY-SYSTEMS
    • ANXIETY-LIKE BEHAVIOR

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