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

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.

Restraint stress is associated with changes in glucocorticoid immunoregulation.

Psychological stress has been associated with activation of the hypothalamic-pituitary-adrenal (HPA) axis and impaired cell-mediated immune (CMI) responses. There is also evidence suggesting that intermittent chronic stress differentially alters CMI across different immune compartments, but the mechanisms underlying this phenomenon have not been explored in detail. In the present study, we investigated (i) acute and chronic restraint stress effects in Sprague-Dawley rats on both peripheral blood lymphocyte (PBL) and splenocyte mitogen-induced proliferation and (ii) also determined whether differential stress effects within these immune compartments might reflect alterations in lymphocyte sensitivity to glucocorticoids. It was found that while acute stress exposure significantly raised plasma corticosterone levels (1048% vs. controls, P<.001), this response was attenuated in the animals previously exposed to chronic intermittent stress (-79.66% vs. acute; P<.001). Acute stress increased phytohemagglutinin (PHA)-induced lymphocyte proliferation in the spleen (69.04%, P=.01) and suppressed PBL proliferation (-45.52%, P<.001). Neither of these changes were observed following chronic stress. We also demonstrated that reexposure to the stressor rapidly increased splenocyte sensitivity to in vitro dexamethasone (P<.05) and corticosterone (P<.05) in chronically stressed rats. Our data (1) confirm that acute stress is associated with compartment-specific changes in CMI function, (2) indicate that chronic stress is associated with habituated endocrine and immune responses and (3) that stressor exposure rapidly alters splenocyte sensitivity to glucocorticoids and we suggest that the latter may contribute to differential stress effects across immune compartments.