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

*Bijbehorende auteur voor dit werk

    Onderzoeksoutputpeer review

    135 Citaten (Scopus)
    429 Downloads (Pure)


    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.

    Originele taal-2English
    Pagina's (van-tot)124-145
    Aantal pagina's22
    TijdschriftFrontiers in Neuroendocrinology
    StatusPublished - apr.-2018

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