Effects of stress hormones on the brain and cognition: Evidence from normal to pathological aging

Souza-Talarico, Juliana Nery de; Marin, Marie‐France; Sindi, Shireen; Lupien, Sonia J.

doi:10.1590/s1980-57642011dn05010003

Cited by 56 publications

(22 citation statements)

References 110 publications

(111 reference statements)

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“…The mental health and well-being consequences of raised cortisol levels are of interest particularly among older people given that some studies find they have higher evening cortisol levels 1 and greater total cortisol output throughout the day 2 compared with younger people though there is interindividual variation in age-related change in cortisol 3 and this may reflect age-related change in disease rather than normal ageing. 4 …”

Section: Introductionmentioning

confidence: 99%

Diurnal cortisol and mental well-being in middle and older age: evidence from four cohort studies

et al. 2017

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ObjectivesWe conducted an individual participant meta-analysis to test the hypothesis that cortisol patterns indicative of dysregulated hypothalamic–pituitary–adrenal axis functioning would be prospectively associated with poorer well-being at follow-up.SettingFour large UK-based cohort studies.ParticipantsThose providing valid salivary or serum cortisol samples (n=7515 for morning cortisol; n=1612 for cortisol awakening response) at baseline (age 44–82) and well-being data on the Warwick Edinburgh Mental Wellbeing Scale at follow-up (0–8 years) were included.ResultsWell-being was not associated with morning cortisol, diurnal slope or awakening response though a borderline association with evening cortisol was found. Adjusting for sex and follow-up time, each 1 SD increase in evening cortisol was associated with a −0.47 (95% CI −1.00 to 0.05) point lower well-being. This was attenuated by adjustment for body mass index, smoking and socioeconomic position. Between-study heterogeneity was low.ConclusionsThis study does not support the hypothesis that diurnal cortisol is prospectively associated with well-being up to 8 years later. However, replication in prospective studies with cortisol samples over multiple days is required.

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Section: Introductionmentioning

confidence: 99%

Diurnal cortisol and mental well-being in middle and older age: evidence from four cohort studies

et al. 2017

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“…Physiologically, GCs are released in a circadian and ultradian manner [13,14]. When stress is chronic, this results in a prolonged exposure to high hormone levels and is associated with severe pathological outcomes [10,68]. Similarly, when GCs are used therapeutically, high doses and repeated long-term exposure causes severe side effects and can result in emerging GC resistance [69,70].…”

Section: Discussionmentioning

confidence: 99%

Glucocorticoid receptor activation induces gene-specific transcriptional memory and universally reversible changes in chromatin accessibility

Bothe

Buschow

Meijsing

2021

Preprint

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Glucocorticoids are stress hormones that elicit cellular responses by binding to the glucocorticoid receptor (GR), a ligand-activated transcription factor. The exposure of cells to this hormone induces wide-spread changes in the chromatin landscape and gene expression. Previous studies have suggested that some of these changes are reversible whereas others persist even when the hormone is no longer around. However, when we examined chromatin accessibility in human airway epithelial cells after hormone washout, we found that the hormone-induced changes were universally reversed after one day. Reversibility of hormone-induced changes are found for GR-occupied opening sites and also for closing sites that typically lack GR occupancy. These closing sites are enriched near repressed genes, suggesting that transcriptional repression by GR does not require nearby GR binding. Mirroring what we say in terms of chromatin accessibility, we found that transcriptional responses to hormone are universally reversable. Moreover, priming of cells by a previous exposure to hormone, in general, did not alter the transcriptional response to a subsequent encounter of the same cue. Interestingly, despite the short-lived nature of hormone-induced changes in the chromatin landscape, we identified a single gene, ZBTB16, that displays transcriptional memory manifesting itself as a more robust transcriptional response upon repeated hormone stimulation. Single-cell analysis revealed that the more robust response is driven by a higher probability of primed cells to activate ZBTB16 and by a subset of cells that express the gene at levels that are higher than the induction levels observed for naïve cells. Although our study shows that hormone-induced changes are typically reversable, exposure to hormone can induce gene-specific changes in the response to subsequent exposures which may play a role in habituation to stressors and changes in glucocorticoid sensitivity.

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“…These varied findings highlight the inter-individual cortisol measurement variability among the elderly. 47 Additionally, timing and methodological differences in sampling cortisol may contribute to contradictory findings, such as location of sampling, time of day of sampling, and salivary versus plasma sampling.…”

Section: Cortisol As a Potential Biomarker Of Stressmentioning

confidence: 99%

“…Both are found in the amygdala responsible for emotional processing, the prefrontal cortex responsible for executive function, and the hippocampus responsible for memory and learning; they are also involved in HPA axis feedback regulation. 46,47 Glucocorticoids have a high-affinity for MR, nearing saturation at basal cortisol levels, whereas GRs activate with high cortisol levels. 48 In the brain, GRs cortisol affinity is one tenth that of MR, and aldosterone's GR affinity is approximately one tenth that of cortisol.…”

Section: Introductionmentioning

confidence: 99%

Stress-Induced Neurodegeneration: The Potential for Coping as Neuroprotective Therapy

Kline

Mega

2020

Am J Alzheimers Dis Other Demen

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Stress responses are essential for survival, but become detrimental to health and cognition with chronic activation. Chronic hypothalamic-pituitary-adrenal axis release of glucocorticoids induces hypothalamic-pituitary-adrenal axis dysfunction and neuronal loss, decreases learning and memory, and modifies glucocorticoid receptor/mineralocorticoid receptor expression. Elderly who report increased stress are nearly 3 times more likely to develop Alzheimer’s disease, have decreased global cognition and faster cognitive decline than those reporting no stress. Patients with mild cognitive impairment are more sensitive to stress compared to healthy elderly and those with Alzheimer’s disease. Stress may also transduce neurodegeneration via the gut microbiome. Coping styles determine hippocampal mineralocorticoid receptor expression in mice, indicating that coping modifies cortisol’s effect on the brain. Identifying neuroprotective coping strategies that lessen the burden of stress may prevent or slow cognitive decline. Treatments and education designed to reduce stress should be recognized as neuroprotective.

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Effects of stress hormones on the brain and cognition: Evidence from normal to pathological aging

Cited by 56 publications

References 110 publications

Diurnal cortisol and mental well-being in middle and older age: evidence from four cohort studies

Diurnal cortisol and mental well-being in middle and older age: evidence from four cohort studies

Glucocorticoid receptor activation induces gene-specific transcriptional memory and universally reversible changes in chromatin accessibility

Stress-Induced Neurodegeneration: The Potential for Coping as Neuroprotective Therapy

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