A single high dose of dexamethasone affects the phosphorylation state of glutamate AMPA receptors in the human limbic system

Mark W Lopes, Rodrigo B Leal, Ricardo Guarnieri, Marcelo L Schwarzbold, Alexandre A Hoeller, Alexandre P Diaz, Gustavo Boos, Katia Lin, Marcelo N Linhares, Jean C Nunes, Joao Quevedo, Zuner A Bortolotto, Hans J Markowitsch, Stafford L Lightman, Roger Walz

Research output: Contribution to journalArticle (Academic Journal)

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Abstract

Glucocorticoids (GC) released during stress response exert feedforward effects in
the whole brain but particularly in the limbic circuits that modulates cognition, emotion and behavior. GC is the most commonly prescribed anti-inflammatory and immunosuppressant medication worldwide and pharmacological GC treatment has been paralleled by the high incidence of acute and chronic neuropsychiatric side effects, which reinforces the brain sensitivity for GC. Synapses can be bi-directionally modifiable via potentiation (LTP, long-term potentiation) or depotentiation (LTD, long-term depression) of synaptic transmission efficacy, and the phosphorylation state of Ser831 and Ser845 sites, in the GluA1 subunit of the glutamate AMPA receptors, are a critical event for these synaptic neuroplasticity events. Through a quasi-randomized controlled study, we show that a single high dexamethasone dose significantly reduces in a dose-dependent manner the levels of GluA1-Ser831 phosphorylation in the amygdala resected during surgery for temporal lobe epilepsy. This is the first report demonstrating GC effects on key markers of synaptic neuroplasticity in the human limbic system. The results contribute to understanding how GC affects the human brain under physiologic and pharmacologic conditions.
Original languageEnglish
Article numbere986
Number of pages9
JournalTranslational Psychiatry
Volume6
Issue number12
Early online date13 Dec 2016
DOIs
Publication statusPublished - Dec 2016

Bibliographical note

15 October 2016

Keywords

  • stress
  • glucocorticoids
  • limbic system
  • synaptic plasticity
  • LTP
  • LTD

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    Lopes, M. W., Leal, R. B., Guarnieri, R., Schwarzbold, M. L., Hoeller, A. A., Diaz, A. P., Boos, G., Lin, K., Linhares, M. N., Nunes, J. C., Quevedo, J., Bortolotto, Z. A., Markowitsch, H. J., Lightman, S. L., & Walz, R. (2016). A single high dose of dexamethasone affects the phosphorylation state of glutamate AMPA receptors in the human limbic system. Translational Psychiatry, 6(12), [e986]. https://doi.org/10.1038/tp.2016.251