Are early stress effects on cognitive processes mediated by the mineralocorticoid or glucocorticoid receptor?
Final Report Abstract
Stress affects essential physiological and psychological processes and leads to an altered processing of information. These effects are mainly mediated via two physiological systems: the fast reacting catecholaminergic system and the slower reacting glucocorticoid system, with cortisol as the main active hormone in humans. Based on the model by Hermans et al., acute stress effects at the brain level are based on two opposing networks: the salience network mediates a rapid mobilization of energy and an outwardly focused attention, especially for potentially harmful stimuli. Immediately after exposure to stress, resources are allocated to this network, resulting in increased activation. During this time window, the executive network is inhibited, which underlies planned and goal-oriented thinking and action. This shift in the distribution of resources is initially and within seconds mediated by catecholaminergic effects, followed by rapid effects of cortisol, which modulate the effects of the catecholamines. Cortisol crosses the blood-brain barrier and binds to two different types of receptors in the brain: the glucocorticoid receptor (GR) and the mineralocorticoid receptor. mineralocorticoid receptor (MR). While the GR has a broad distribution in the brain, the MR is predominantly found in limbic structures and the prefrontal cortex, i.e. brain regions with high importance for cognitive and emotional processes. Numerous animal and human studies have shown an influence of the membrane-bound MR in mediating early stress effects and a role in rapid cortisol effects. Although these early effects are generally attributed to the MR, animal studies also suggest a role for the GR in mediating rapid cortisol effects. These are also potentially induced via membrane-bound GR in a nongenomic way. These effects, which are specific to function and brain region, should differ between the two receptor types. It can be assumed that a reduction of neuronal activation is mediated via the GR and an increase via the MR. In our conducted project, we studied the influence of stress in combination with the selective blockade of either MR or GR to systematically investigate receptor-specific cortisol effects on various emotional and cognitive processes. These can be assigned primarily to the salience network (attention to emotional stimuli), the executive network (working memory: n-back) or both networks (decisions in risky situations). We found specific effects of receptor blockade on the autoregulation of cortisol secretion, with MR blockade using spironolactone leading to a significant increase in cortisol secretion. This was in contrast to the unchanged cortisol response after GR blockade. We discuss this effect in terms of receptor-specific influence on hypothalamic feedback control of cortisol secretion after stress. Stress led to riskier decisions, an effect that was mitigated by MR blockade. This could be an indication of the role of cortisol in mediating stress effects in this domain and the role of the MR receptor. We found no effects of stress on working memory performance and attention to emotional stimuli.
Publications
-
The influence of pharmacological mineralocorticoid and glucocorticoid receptor blockade on the cortisol response to psychological stress. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 129, 110905.
Deuter, Christian E.; Kaczmarczyk, Michael; Hellmann-Regen, Julian; Kuehl, Linn K.; Wingenfeld, Katja & Otte, Christian
