Actions and Interactions of Estradiol and Glucocorticoids in Cognition and the Brain: Implications for Aging Women

Overview

Journal Neurosci Biobehav Rev

Specialties Neurology
Psychology
Social Sciences

Date 2015 May 2

PMID 25929443

Citations 24

Authors

Alexandra Ycaza Herrera

Mara Mather

Affiliations

Soon will be listed here.

Abstract

Menopause involves dramatic declines in estradiol production and levels. Importantly, estradiol and the class of stress hormones known as glucocorticoids exert countervailing effects throughout the body, with estradiol exerting positive effects on the brain and cognition, glucocorticoids exerting negative effects on the brain and cognition, and estradiol able to mitigate negative effects of glucocorticoids. Although the effects of these hormones in isolation have been extensively studied, the effects of estradiol on the stress response and the neuroprotection offered against glucocorticoid exposure in humans are less well known. Here we review evidence suggesting that estradiol-related protection against glucocorticoids mitigates stress-induced interference with cognitive processes. Animal and human research indicates that estradiol-related mitigation of glucocorticoid damage and interference is one benefit of estradiol supplementation during peri-menopause or soon after menopause. The evidence for estradiol-related protection against glucocorticoids suggests that maintaining estradiol levels in post-menopausal women could protect them from stress-induced declines in neural and cognitive integrity.

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References

Lindheim S, Legro R, Bernstein L, Stanczyk F, Vijod M, Presser S . Behavioral stress responses in premenopausal and postmenopausal women and the effects of estrogen. Am J Obstet Gynecol. 1992; 167(6):1831-6. DOI: 10.1016/0002-9378(92)91783-7. View

Herman J, Patel P, Akil H, Watson S . Localization and regulation of glucocorticoid and mineralocorticoid receptor messenger RNAs in the hippocampal formation of the rat. Mol Endocrinol. 1989; 3(11):1886-94. DOI: 10.1210/mend-3-11-1886. View

Bimonte H, Denenberg V . Estradiol facilitates performance as working memory load increases. Psychoneuroendocrinology. 1999; 24(2):161-73. DOI: 10.1016/s0306-4530(98)00068-7. View

Chen S, Nilsen J, Brinton R . Dose and temporal pattern of estrogen exposure determines neuroprotective outcome in hippocampal neurons: therapeutic implications. Endocrinology. 2006; 147(11):5303-13. DOI: 10.1210/en.2006-0495. View

Diaz Brinton R, Chen S, Montoya M, Hsieh D, Minaya J, Kim J . The women's health initiative estrogen replacement therapy is neurotrophic and neuroprotective. Neurobiol Aging. 2000; 21(3):475-96. DOI: 10.1016/s0197-4580(00)00109-3. View

Smith Y, Zubieta J . Neuroimaging of aging and estrogen effects on central nervous system physiology. Fertil Steril. 2001; 76(4):651-9. DOI: 10.1016/s0015-0282(01)01985-9. View

McMorris T, Sproule J, Turner A, Hale B . Acute, intermediate intensity exercise, and speed and accuracy in working memory tasks: a meta-analytical comparison of effects. Physiol Behav. 2010; 102(3-4):421-8. DOI: 10.1016/j.physbeh.2010.12.007. View

Lighthall N, Mather M, Gorlick M . Acute stress increases sex differences in risk seeking in the balloon analogue risk task. PLoS One. 2009; 4(7):e6002. PMC: 2698212. DOI: 10.1371/journal.pone.0006002. View

Puder J, Freda P, Goland R, Wardlaw S . Estrogen modulates the hypothalamic-pituitary-adrenal and inflammatory cytokine responses to endotoxin in women. J Clin Endocrinol Metab. 2001; 86(6):2403-8. DOI: 10.1210/jcem.86.6.7528. View

10.

Yaffe K, Vittinghoff E, Ensrud K, Johnson K, Diem S, Hanes V . Effects of ultra-low-dose transdermal estradiol on cognition and health-related quality of life. Arch Neurol. 2006; 63(7):945-50. DOI: 10.1001/archneur.63.7.945. View

11.

Bingaman E, Magnuson D, Gray T, Handa R . Androgen inhibits the increases in hypothalamic corticotropin-releasing hormone (CRH) and CRH-immunoreactivity following gonadectomy. Neuroendocrinology. 1994; 59(3):228-34. DOI: 10.1159/000126663. View

12.

Bowman R, Beck K, Luine V . Chronic stress effects on memory: sex differences in performance and monoaminergic activity. Horm Behav. 2003; 43(1):48-59. DOI: 10.1016/s0018-506x(02)00022-3. View

13.

Symonds C, McKie S, Elliott R, Deakin J, Anderson I . Detection of the acute effects of hydrocortisone in the hippocampus using pharmacological fMRI. Eur Neuropsychopharmacol. 2012; 22(12):867-74. DOI: 10.1016/j.euroneuro.2012.03.008. View

14.

Kleen J, Sitomer M, Killeen P, Conrad C . Chronic stress impairs spatial memory and motivation for reward without disrupting motor ability and motivation to explore. Behav Neurosci. 2006; 120(4):842-51. PMC: 1578508. DOI: 10.1037/0735-7044.120.4.842. View

15.

Tombaugh G, Yang S, Swanson R, Sapolsky R . Glucocorticoids exacerbate hypoxic and hypoglycemic hippocampal injury in vitro: biochemical correlates and a role for astrocytes. J Neurochem. 1992; 59(1):137-46. DOI: 10.1111/j.1471-4159.1992.tb08884.x. View

16.

Weiser M, Handa R . Estrogen impairs glucocorticoid dependent negative feedback on the hypothalamic-pituitary-adrenal axis via estrogen receptor alpha within the hypothalamus. Neuroscience. 2009; 159(2):883-95. PMC: 5837863. DOI: 10.1016/j.neuroscience.2008.12.058. View

17.

Pasquali R, Vicennati V, Cacciari M, Pagotto U . The hypothalamic-pituitary-adrenal axis activity in obesity and the metabolic syndrome. Ann N Y Acad Sci. 2006; 1083:111-28. DOI: 10.1196/annals.1367.009. View

18.

Oei N, Everaerd W, Elzinga B, van Well S, Bermond B . Psychosocial stress impairs working memory at high loads: an association with cortisol levels and memory retrieval. Stress. 2006; 9(3):133-41. DOI: 10.1080/10253890600965773. View

19.

Woolley C, Gould E, McEwen B . Exposure to excess glucocorticoids alters dendritic morphology of adult hippocampal pyramidal neurons. Brain Res. 1990; 531(1-2):225-31. DOI: 10.1016/0006-8993(90)90778-a. View

20.

Butts K, Weinberg J, Young A, Phillips A . Glucocorticoid receptors in the prefrontal cortex regulate stress-evoked dopamine efflux and aspects of executive function. Proc Natl Acad Sci U S A. 2011; 108(45):18459-64. PMC: 3215005. DOI: 10.1073/pnas.1111746108. View