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

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

Translational psychiatry (2016-12-14)
M W Lopes, R B Leal, R Guarnieri, M L Schwarzbold, A Hoeller, A P Diaz, G L Boos, K Lin, M N Linhares, J C Nunes, J Quevedo, Z A Bortolotto, H J Markowitsch, S L Lightman, R Walz
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 are 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 (long-term potentiation, LTP) or depotentiation (long-term depression, LTD) 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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Anti-phospho-AMPA Receptor, GluR1 Subunit (pSer845) antibody produced in rabbit, affinity isolated antibody, buffered aqueous glycerol solution
Sigma-Aldrich
Anti-phospho-AMPA Receptor, GluR1 Subunit (pSer831) antibody produced in rabbit, ~1 mg/mL, affinity isolated antibody, buffered aqueous solution
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Anti-p38 MAP Kinase antibody produced in rabbit, IgG fraction of antiserum, buffered aqueous solution
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Anti-JNK, Activated (Diphosphorylated JNK) antibody, Mouse monoclonal, clone JNK-PT48, purified from hybridoma cell culture
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Monoclonal Anti-MAP Kinase, Activated (Diphosphorylated ERK-1&2) antibody produced in mouse, clone MAPK-YT, ascites fluid
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Anti-MAP Kinase (ERK-1, ERK-2) antibody produced in rabbit, whole antiserum
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Anti-phospho-p38α(Thr180/Tyr182) Antibody, clone 8.78.8, rabbit monoclonal, culture supernatant, clone 8.78.8, from rabbit