Estrogens regulate neuroinflammatory genes via estrogen receptors α and β in the frontal cortex of middle-aged female rats

Sárvári, Miklós; Hrabovszky, Erik; Kalló, Imre; Solymosi, Norbert; Tóth, Kinga; Láng, István; Széles, János; Mahó, Sándor; Molnár, Béla; Liposits, Zsolt

doi:10.1186/1742-2094-8-82

Cited by 67 publications

(47 citation statements)

References 78 publications

(103 reference statements)

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“…Concentrations of E2 and isotype-selective ER agonists were calculated to produce a release rate of 2.0µg/d and 20 µg/d, respectively. Treatments with E2 and LE2 at these doses result in a similar increase in uterine weight, while DPN causes no change [43]. Body weights were measured to test efficacy of the treatments.…”

Section: Methodsmentioning

confidence: 99%

Ovariectomy and Subsequent Treatment with Estrogen Receptor Agonists Tune the Innate Immune System of the Hippocampus in Middle-Aged Female Rats

et al. 2014

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The innate immune system including microglia has a major contribution to maintenance of the physiological functions of the hippocampus by permanent monitoring of the neural milieu and elimination of tissue-damaging threats. The hippocampus is vulnerable to age-related changes ranging from gene expression to network connectivity. The risk of hippocampal deterioration increases with the decline of gonadal hormone supply. To explore the impact of hormone milieu on the function of the innate immune system in middle-aged female rats, we compared mRNA expression in the hippocampus after gonadal hormone withdrawal, with or without subsequent estrogen replacement using estradiol and isotype-selective estrogen receptor (ER) agonists. Targeted profiling assessed the status of the innate immune system (macrophage-associated receptors, complement, inhibitory neuronal ligands), local estradiol synthesis (P450 aromatase) and estrogen reception (ER). Results established upregulation of macrophage-associated (Cd45, Iba1, Cd68, Cd11b, Cd18, Fcgr1a, Fcgr2b) and complement (C3, factor B, properdin) genes in response to ovariectomy. Ovariectomy upregulated Cd22 and downregulated semaphorin3A (Sema3a) expression, indicating altered neuronal regulation of microglia. Ovariectomy also led to downregulation of aromatase and upregulation of ERα gene. Of note, analogous changes were observed in the hippocampus of postmenopausal women. In ovariectomized rats, estradiol replacement attenuated Iba1, Cd11b, Fcgr1a, C3, increased mannose receptor Mrc1, Cd163 and reversed Sema3a expression. In contrast, reduced expression of aromatase was not reversed by estradiol. While the effects of ERα agonist closely resembled those of estradiol, ERβ agonist was also capable of attenuating the expression of several macrophage-associated and complement genes. These data together indicate that the innate immune system of the aging hippocampus is highly responsive to the gonadal hormone milieu. In ovariectomized female rats, estradiol replacement exerts potent immunomodulatory effects including attenuation of microglia sensitization, initiation of M2-like activation and modulation of complement expression by targeting hippocampal neurons and glial cells through ERα and ERβ.

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Section: Methodsmentioning

confidence: 99%

Ovariectomy and Subsequent Treatment with Estrogen Receptor Agonists Tune the Innate Immune System of the Hippocampus in Middle-Aged Female Rats

et al. 2014

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“…Another group examining neuro-cortical outcomes in rodents found that ERα agonists regulated S100A8/A9 gene expression, which suggested an estrogenic link [85]. However, the regulation of S100A8/A9 in human skin remains unclear as to the estrogenic mechanism of regulation via the ER subtypes.…”

Section: Human Skin Gene Expressionmentioning

confidence: 99%

Resveratrol, 4′ Acetoxy Resveratrol, R-equol, Racemic Equol or S-equol as Cosmeceuticals to Improve Dermal Health

Lephart

2017

IJMS

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Phytochemicals are botanical compounds used in dermatology applications as cosmeceuticals to improve skin health. Resveratrol and equol are two of the best-known polyphenolic or phytoestrogens having similar chemical structures and some overlapping biological functions to 17β-estradiol. Human skin gene expression was reviewed for 28 different biomarkers when resveratrol, 4′ acetoxy resveratrol (4AR), R-equol, racemic equol or S-equol were tested. Sirtuin 1 activator (SIRT 1) was stimulated by resveratrol and 4AR only. Resveratrol, R-equol and racemic equol were effective on the aging biomarkers proliferating cell nuclear factor (PCNA), nerve growth factor (NGF), 5α-reductase and the calcium binding proteins S100 A8 and A9. Racemic equol and 4AR displayed among the highest levels for the collagens, elastin and tissue inhibitor of the matrix metalloproteinase 1 (TIMP 1). S-equol displayed the lowest level of effectiveness compared to the other compounds. The 4AR analog was more effective compared to resveratrol by 1.6-fold. R-equol and racemic equol were almost equal in potency displaying greater inhibition vs. resveratrol or its 4′ analog for the matrix metalloproteinases (MMPs), but among the inflammatory biomarkers, resveratrol, 4AR, R-equol and racemic equol displayed high inhibition. Thus, these cosmeceuticals display promise to improve dermal health; however, further study is warranted to understand how phytochemicals protect/enhance the skin.

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“…Recent studies indicate novel roles for estrogens in the regulation of neuroendocrine, autonomic and behavioral responses to stress. In this regard, estrogens have also been shown to modulate related functions such as inflammatory processes, pain, anxiety, depressive-like behaviors and cognitive function (1–4). In this review, we focus on some of the roles for estrogens and estrogen receptors (ERs) in the control of stress and stress-related behaviors and address a few of the molecular mechanisms that might drive these regulatory processes.…”

Section: Introductionmentioning

confidence: 99%

Estrogen Receptors and the Regulation of Neural Stress Responses

2012

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It is now well established that estrogens can influence a panoply of physiological and behavioral functions. In many instances, the effects of estrogens are mediated by the ‘classical’ actions of two different estrogen receptors (ERs), ERα or ERβ. ERα and ERβ appear to have opposing actions in the control of stress responses and modulate different neurotransmitter or neuropeptide systems. Studies elucidating the molecular mechanisms for such regulatory processes are currently in progress. Furthermore, the use of ERα and ERβ knockout mouse lines has allowed the exploration of the importance of these receptors in behavioral responses such as anxiety-like and depressive-like behaviors. This review examines some of the recent advances in our knowledge of hormonal control of neuroendocrine and behavioral responses to stress and underscore the importance of these receptors as future therapeutic targets for control of stress-related signaling pathways.

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Estrogens regulate neuroinflammatory genes via estrogen receptors α and β in the frontal cortex of middle-aged female rats

Cited by 67 publications

References 78 publications

Ovariectomy and Subsequent Treatment with Estrogen Receptor Agonists Tune the Innate Immune System of the Hippocampus in Middle-Aged Female Rats

Ovariectomy and Subsequent Treatment with Estrogen Receptor Agonists Tune the Innate Immune System of the Hippocampus in Middle-Aged Female Rats

Resveratrol, 4′ Acetoxy Resveratrol, R-equol, Racemic Equol or S-equol as Cosmeceuticals to Improve Dermal Health

Estrogen Receptors and the Regulation of Neural Stress Responses

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