The role of mineralocorticoid receptors in the circadian activity of the human hypothalamus–pituitary–adrenal system:

Heuser, Isabella; Deuschle, Michael; Weber, A. F.; Kniest, Anja; Ziegler, Christina; Weber, Bernhard; Colla, Michael

doi:10.1016/s0197-4580(00)00145-7

Cited by 38 publications

(18 citation statements)

References 20 publications

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“…In rats and dogs it has been shown that MR expression in the hippocampus is reduced in aged animals (Rothuizen et al, 1993;Yau et al, 2002). Consistent with these findings, aged humans showed diminished MR-mediated inhibition on cortisol secretion (Heuser et al, 2000a, b;Otte et al, 2003). Thus, diminished MR expression may contribute to cognitive deficits in aging and depression.…”

Section: Discussionmentioning

confidence: 60%

“…Also, after CRH stimulation (Arvat et al, 2001;Kellner et al, 2002a, b) as well as in a combined dexamethasone suppression/CRH stimulation test (Heuser et al, 2000a, b) and during exercise (Wellhoener et al, 2004) significant elevations of plasma cortisol after prior anti-MR treatment have been reported. Although in our study subjects started with much higher baseline cortisol levels during the spironolactone condition, the increase of ACTH was not different between conditions.…”

Section: Discussionmentioning

confidence: 99%

“…Most studies (Deuschle et al, 1998;Heuser et al, 2000a, b;Kellner et al, 2002a, b;Young et al, 1998) have shown elevated basal plasma cortisol concentrations after administration of spironolactone, a MR antagonist. Also, after CRH stimulation (Arvat et al, 2001;Kellner et al, 2002a, b) as well as in a combined dexamethasone suppression/CRH stimulation test (Heuser et al, 2000a, b) and during exercise (Wellhoener et al, 2004) significant elevations of plasma cortisol after prior anti-MR treatment have been reported.…”

Section: Introductionmentioning

confidence: 99%

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Blockade of the Mineralocorticoid Receptor in Healthy Men: Effects on Experimentally Induced Panic Symptoms, Stress Hormones, and Cognition

Otte

Moritz

Yassouridis

et al. 2006

Neuropsychopharmacol

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Animal studies have shown that blockade of central mineralocorticoid receptors (MR) has anxiolytic effects and impairs several aspects of cognitive function. No study to date assessed the effects of MR blockade on anxiety and cognitive function in humans. In the present study, 16 healthy young men were treated either with placebo or with 300 mg spironolactone, a MR-antagonist, at 1100, 1330, and 1630 hours in a balanced cross-over design with the two study conditions being 1 week apart. At 1500 hours, the panic symptoms provoking compound cholecystokinin-tetrapeptide (CCK-4) was administered i.v. on both occasions and panic symptoms were assessed. We measured plasma ACTH and cortisol between 1300 and 1900 hours and assessed cognitive function between 1800 and 1900 hours. CCK-4 elicited panic symptoms and increased ACTH and cortisol secretion in both conditions. Intensity of panic symptoms after CCK-4 was not different between spironolactone and placebo. Spironolactone significantly impaired selective attention and delayed recall of visuospatial memory, and diminished set shifting/mental flexibility on a trend level. Pretreatment with spironolactone led to higher baseline cortisol levels compared to placebo whereas no differences in stimulated cortisol, baseline ACTH, and stimulated ACTH emerged. Blockade of MR with spironolactone increases baseline cortisol secretion and impairs cognitive function but has no effect on experimentally induced panic symptoms in humans, for the study design and dosage of spironolactone used. The domains of cognitive function that are impaired after blockade of MR in men, that is, selective attention, visuospatial memory, and mental flexibility/set shifting appear to be remarkably similar to those described in animal studies.

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Section: Discussionmentioning

confidence: 60%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Blockade of the Mineralocorticoid Receptor in Healthy Men: Effects on Experimentally Induced Panic Symptoms, Stress Hormones, and Cognition

Otte

Moritz

Yassouridis

et al. 2006

Neuropsychopharmacol

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“…These receptors are expressed throughout the brain with concentrated expression in the PVN, hippocampal area and dentate gyrus, amygdala and lateral septum and prefrontal cortex (PFC) (Pillai et al 2012). Mineralocorticoid receptors (MR), expressed only in the hippocampus and the lateral septum, have a tenfold greater affinity for cortisol and are primarily active at basal level and important in modulating the circadian pulsatile rhythm of cortisol (Deuschle et al 1998;Heuser et al 2000).…”

Section: Neurobiology Of Stressmentioning

confidence: 99%

Stress, Schizophrenia and Bipolar Disorder

Green

Girshkin

Teroganova

et al. 2014

Behavioral Neurobiology of Stress-Related Disorders

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The role of stress in precipitating psychotic episodes in schizophrenia and bipolar disorder has long been acknowledged. However, the neurobiological mechanism/s of this association have remained elusive. Current neurodevelopmental models of psychosis implicate early dysfunction in biological systems regulating hypothalamic-pituitary-adrenal axis and immune function, with long-term effects on the development of the brain networks responsible for higher order cognitive processes and stress reactivity in later life. There is also increasing evidence of childhood trauma in psychosis, and its impact on the development of brain systems regulating stress. These findings are emerging in the context of a new era of epigenetic methods facilitating the study of environmental effects on gene expression. The evidence is thus converging: exposure to stress at critical periods in life may be an important factor in the development of the brain dysfunction that represents psychosis vulnerability, rather than merely interacting with an independent 'biological vulnerability' to manifest in psychosis.

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“…It is possible that the increased vulnerability to stroke in elderly is linked to the cumulative effects of adverse experiences, such as stress, during a life-time [7,8]. In addition, ageing may be associated with gradual dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis leading to elevated glucocorticoid levels in elderly [9][10][11]. Increased basal circulating stress hormone levels [12] may contribute to age-related functional decline [13][14][15].…”

Section: Introductionmentioning

confidence: 99%

Synergistic effects of age and stress in a rodent model of stroke

Merrett

Kirkland

Metz

2010

Behavioural Brain Research

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Ageing and stress represent critical influences on stroke risk and outcome. These variables are intricately linked, as ageing is frequently associated with gradual dysregulation of the hypothalamic-pituitary-adrenal axis. This study determined the effects of stress on motor function in aged rats, and explored possible interactions of age and stress on motor recovery following stroke in a rat model. Young adult (4 months) and aged (18 months) male Wistar rats were tested in skilled and non-skilled movement before and after focal ischemia in motor cortex. One group of each age received restraint stress starting seven days pre-lesion until three weeks post-lesion. Aged rats were less mobile and stress further diminished their overall exploratory activity. Aged rats were also less proficient in motor skill acquisition and slower to improve after lesion. Stress diminished post-lesion improvement and prevented recovery of endpoint measures. The larger functional loss in aged rats vs. young rats was accompanied by greater damage of cortical tissue and persistent elevations in corticosterone levels. The behavioural and physiological measures suggest limited ability of aged animals to adapt to chronic stress. These findings show that age or stress alone can modulate motor performance but may have greater influence by synergistically affecting stroke recovery.

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The role of mineralocorticoid receptors in the circadian activity of the human hypothalamus–pituitary–adrenal system:

Cited by 38 publications

References 20 publications

Blockade of the Mineralocorticoid Receptor in Healthy Men: Effects on Experimentally Induced Panic Symptoms, Stress Hormones, and Cognition

Blockade of the Mineralocorticoid Receptor in Healthy Men: Effects on Experimentally Induced Panic Symptoms, Stress Hormones, and Cognition

Stress, Schizophrenia and Bipolar Disorder

Synergistic effects of age and stress in a rodent model of stroke

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