Epigenetic regulation of estrogen receptor beta expression in the rat cortex during aging

Westberry, Jenne M.; Trout, Amanda L; Wilson, Melinda E.

doi:10.1097/wnr.0b013e328346e1cf

Cited by 20 publications

(16 citation statements)

References 23 publications

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“…DNMT3A levels peak at PN 10 and fall back to low expression by PN 25, while DNMT 1 levels increase concomitantly and remain high in adulthood. A similar increased methylation and reduced expression of ERβ has been reported throughout the cortex during the natural progression of reduced circulating hormones in aging (Westberry et al, 2011). This increased ERβ methylation was also associated with increased cortical DNMT 1 and 3α expression, again suggesting a mechanism whereby local methylation levels are interrelated with gonadal status.…”

Section: Maturation Of the Nervous System During Pubertysupporting

confidence: 73%

“…Increased methylation has been associated with decreased expression of the estrogen receptor alpha (ERα), estrogen receptor beta (ERβ), and the progesterone receptor (Prewitt and Wilson, 2007; Westberry et al, 2011; 2010). The developmental time course of methylation of these genes has been examined in the rat.…”

Section: Maturation Of the Nervous System During Pubertymentioning

confidence: 99%

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Epigenetic mechanisms in pubertal brain maturation

et al. 2014

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Puberty is a critical period of development during which the reemergence of gonadotropin releasing hormone secretion from the hypothalamus triggers a cascade of hormone-dependent processes. Maturation of specific brain regions including the prefrontal cortex occurs during this window, but the complex mechanisms underlying these dynamic changes are not well understood. Particularly, the potential involvement of epigenetics in this programming has been under-examined. The epigenome is known to guide earlier stages of development, and it is similarly poised to regulate vital pubertal-driven brain maturation. Further, as epigenetic machinery is highly environmentally responsive, its involvement may also lend this period of growth to greater vulnerability to external insults, resulting in reprogramming and increased disease risk. Importantly, neuropsychiatric diseases commonly present in individuals during or immediately following puberty, and environmental perturbations including stress may precipitate disease onset by disrupting the normal trajectory of pubertal brain development via epigenetic mechanisms. In this review, we discuss epigenetic processes involved in pubertal brain maturation, the potential points of derailment, and the importance of future studies for understanding this dynamic developmental window and gaining a better understanding of neuropsychiatric disease risk.

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Section: Maturation Of the Nervous System During Pubertysupporting

confidence: 73%

Section: Maturation Of the Nervous System During Pubertymentioning

confidence: 99%

Epigenetic mechanisms in pubertal brain maturation

et al. 2014

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“…The expression of ERα is highly regulated by methylation during early post-natal development in mice (Westberry and Wilson, 2012). More relevant for aging, methylation of the ERβ promoter is increased in the neocortex of middle-aged, but not young, female rats (Westberry et al, 2011). This increased methylation was associated with reduced ERβ mRNA.…”

Section: Future Directionsmentioning

confidence: 99%

Epigenetic regulation of estrogen-dependent memory

Fortress

Frick

2014

Frontiers in Neuroendocrinology

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Hippocampal memory formation is highly regulated by post-translational histone modifications and DNA methylation. Accordingly, these epigenetic processes play a major role in the effects of modulatory factors, such as sex steroid hormones, on hippocampal memory. Our laboratory recently demonstrated that the ability of the potent estrogen 17β-estradiol (E2) to enhance hippocampal-dependent novel object recognition memory in ovariectomized female mice requires ERK-dependent histone H3 acetylation and DNA methylation in the dorsal hippocampus. Although these data provide valuable insight into the chromatin modifications that mediate the memory-enhancing effects of E2, epigenetic regulation of gene expression is enormously complex. Therefore, more research is needed to fully understand how E2 and other hormones employ epigenetic alterations to shape behavior. This review discusses the epigenetic alterations shown thus far to regulate hippocampal memory, briefly reviews the effects of E2 on hippocampal function, and describes in detail our work on epigenetic regulation of estrogenic memory enhancement.

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“…In general, most reports suggest that aging decreases ER β expression, but, like ER α , this effect may be highly region specific. An age-related decrease in ER β expression in the brain is underscored by a corresponding increase in CpG methylation of the ESR2 promoter in middle-aged (9–12 months) rats [69]. Other reports describe decreases in ER β protein and message in some areas but not in others [63, 70].…”

Section: Expression Of Ers In the Brain: A Complex Storymentioning

confidence: 99%

Estrogen Signaling and the Aging Brain: Context-Dependent Considerations for Postmenopausal Hormone Therapy

Mott

Pak

2013

ISRN Endocrinology

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Recent clinical studies have spurred rigorous debate about the benefits of hormone therapy (HT) for postmenopausal women. Controversy first emerged based on a sharp increase in the risk of cardiovascular disease in participants of the Women's Health Initiative (WHI) studies, suggesting that decades of empirical research in animal models was not necessarily applicable to humans. However, a reexamination of the data from the WHI studies suggests that the timing of HT might be a critical factor and that advanced age and/or length of estrogen deprivation might alter the body's ability to respond to estrogens. Dichotomous estrogenic effects are mediated primarily by the actions of two high-affinity estrogen receptors alpha and beta (ERα & ERβ). The expression of the ERs can be overlapping or distinct, dependent upon brain region, sex, age, and exposure to hormone, and, during the time of menopause, there may be changes in receptor expression profiles, post-translational modifications, and protein:protein interactions that could lead to a completely different environment for E2 to exert its effects. In this review, factors affecting estrogen-signaling processes will be discussed with particular attention paid to the expression and transcriptional actions of ERβ in brain regions that regulate cognition and affect.

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Epigenetic regulation of estrogen receptor beta expression in the rat cortex during aging

Cited by 20 publications

References 23 publications

Epigenetic mechanisms in pubertal brain maturation

Epigenetic mechanisms in pubertal brain maturation

Epigenetic regulation of estrogen-dependent memory

Estrogen Signaling and the Aging Brain: Context-Dependent Considerations for Postmenopausal Hormone Therapy

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