Estradiol responsiveness of synaptopodin in hippocampal neurons is mediated by estrogen receptor β

Fester, Lars; Labitzke, Jan; Hinz, Rebecca; Behem, Christoph; Horling, Katja; Bernhard, Theresa; Bader, Manuela I.; Vollmer, Günter; Rune, Gabriele M.

doi:10.1016/j.jsbmb.2013.09.004

Cited by 14 publications

(13 citation statements)

References 53 publications

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“…Therefore, we suggest that low levels of ERα associated with the high-cholesterol diet in our study could be responsible for a reduction in the post-synaptic marker PSD-95. Additionally, upregulation of ERβ has been shown to have a negative effect on synaptic function by downregulating synaptopodin, an actin associated post-synaptic protein [76]. The increase in ERβ levels and the decreased number of mitochondria observed in our study are presumably connected because it has been shown that mitochondrial ERβ can have detrimental effects on mitochondrial function [77].…”

Section: Discussionmentioning

confidence: 63%

A High-Cholesterol Diet Increases 27-Hydroxycholesterol and Modifies Estrogen Receptor Expression and Neurodegeneration in Rabbit Hippocampus

Brooks

Dykes

Schreurs

2017

JAD

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Hypercholesterolemia has been implicated in numerous health problems from cardiovascular disease to neurodegeneration. High serum cholesterol levels in midlife have been associated with an increased risk of developing Alzheimer’s disease (AD) later in life which suggests that the pathways leading to AD pathology might be activated decades before the symptoms of the disease are detected. Cholesterol-fed animals, particularly cholesterol-fed rabbits, exhibit brain pathology similar to the changes found in brains of AD patients. Dietary cholesterol, which cannot pass the blood-brain barrier, is thought to influence central nervous system homeostasis by increased transport of its circulatory breakdown product, 27-hydroxycholesterol (27-OHC), into the brain. 27-OHC is an endogenous selective estrogen receptor modulator. Estrogen-mediated non-reproductive functions require estrogen receptors (ERs) and include modulation of mitochondrial function and structure, as well as regulation of synaptogenesis in the brain. ERs are located in brain areas affected early in AD pathogenesis, including the hippocampus. Here we report that increase in serum cholesterol, induced by feeding rabbits a high-cholesterol diet, is associated with higher levels of 27-OHC in the brain as well as increased levels of neurodegeneration in the hippocampus. Furthermore, these results are accompanied by changes in expression of ERs in the hippocampus as well as a decrease in hippocampal mitochondria. These findings provide an important insight into one of the possible mechanisms involved in the development of AD, and shed light on the processes that may antedate amyloid-β and tau phosphorylation changes currently hypothesized to cause AD symptomology and pathology.

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Section: Discussionmentioning

confidence: 63%

A High-Cholesterol Diet Increases 27-Hydroxycholesterol and Modifies Estrogen Receptor Expression and Neurodegeneration in Rabbit Hippocampus

Brooks

Dykes

Schreurs

2017

JAD

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“…So it can be concluded that ER α mainly mediated the function of estrogen in reproductive tissues, while the effect of estrogen in other tissues such as brain was mediated by ER β . From the physiological aspect, in addition to the role in the reproductive system, ER β plays a major role in proliferation and differentiation of neurons, astrocytes, and female reproductive cells [14]. In the brain, estrogen receptor ER α and ER β mediated the persistent regulation of estrogen to nerve cells in the target gene transcription, and cells in anterior and middle hypophysis are targets of estrogen action.…”

Section: Discussionmentioning

confidence: 99%

Preliminary Study of Quercetin Affecting the Hypothalamic‐Pituitary‐Gonadal Axis on Rat Endometriosis Model

Cao

Zhuang

Yang

et al. 2014

Evidence-Based Complementary and Alternative Medicine

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In this study, the endometriosis rats model was randomly divided into 6 groups: model control group, ovariectomized group, Gestrinone group, and quercetin high/medium/low dose group. Rats were killed after 3 weeks of administration. The expression levels of serum FSH and LH were detected by ELISA. The localizations and quantities of ERα, ERβ, and PR were detected by immunohistochemistry and western blot. The results showed that the mechanism of quercetin inhibiting the growth of ectopic endometrium on rat endometriosis model may be through the decreasing of serum FSH and LH levels and then reducing local estrogen content to make the ectopic endometrium atrophy. Quercetin can decrease the expression of ERα, ERβ, and PR in hypothalamus, pituitary, and endometrium, thereby inhibiting estrogen and progesterone binding to their receptors to play the role of antiestrogen and progesterone.

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“…The gene motif of estrogen target has been found in the promoter of insulin, suggesting that estrogen can directly regulate insulin expression [21]. Estrogen can also enhance insulin sensitivity by phosphorylating insulin receptors [22]. These findings suggested that estrogen can regulate insulin production and signals.…”

Section: Discussionmentioning

confidence: 96%

“…These findings suggested that estrogen can regulate insulin production and signals. Some studies have indicated that the regulatory effect of estrogen on synaptic plasticity is mediated by ERβ [22]. Synaptic plasticity is one of the critical foundations in learning and memory [23].…”

Section: Discussionmentioning

confidence: 99%

Spatial Memory Impairment Is Associated with Hippocampal Insulin Signals in Ovariectomized Rats

et al. 2014

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Estrogen influences memory formation and insulin sensitivity. Meanwhile, glucose utilization directly affects learning and memory, which are modulated by insulin signals. Therefore, this study investigated whether or not the effect of estrogen on memory is associated with the regulatory effect of this hormone on glucose metabolism. The relative expression of estrogen receptor β (ERβ) and glucose transporter type 4 (GLUT4) in the hippocampus of rats were evaluated by western blot. Insulin level was assessed by ELISA and quantitative RT-PCR, and spatial memory was tested by the Morris water maze. Glucose utilization in the hippocampus was measured by 2-NBDG uptake analysis. Results showed that ovariectomy impaired the spatial memory of rats. These impairments are similar as the female rats treated with the ERβ antagonist tamoxifen (TAM). Estrogen blockade by ovariectomy or TAM treatment obviously decreased glucose utilization. This phenomenon was accompanied by decreased insulin level and GLUT4 expression in the hippocampus. The female rats were neutralized with hippocampal insulin with insulin antibody, which also impaired memory and local glucose consumption. These results indicated that estrogen blockade impaired the spatial memory of the female rats. The mechanisms by which estrogen blockade impaired memory partially contributed to the decline in hippocampal insulin signals, which diminished glucose consumption.

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Estradiol responsiveness of synaptopodin in hippocampal neurons is mediated by estrogen receptor β

Cited by 14 publications

References 53 publications

A High-Cholesterol Diet Increases 27-Hydroxycholesterol and Modifies Estrogen Receptor Expression and Neurodegeneration in Rabbit Hippocampus

A High-Cholesterol Diet Increases 27-Hydroxycholesterol and Modifies Estrogen Receptor Expression and Neurodegeneration in Rabbit Hippocampus

Preliminary Study of Quercetin Affecting the Hypothalamic‐Pituitary‐Gonadal Axis on Rat Endometriosis Model

Spatial Memory Impairment Is Associated with Hippocampal Insulin Signals in Ovariectomized Rats

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