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ER (estrogen receptors) in the brain. Most receptors are located in the Cb (cerebellum), PFC (prefrontal cortex), Hip (hippocampus), and Amy (amygdala). ERα is located in the Amy and hypothalamus, whereas ERβ is found mainly in the Hip. In the Cb and thalamus, both receptors are expressed simultaneously. Created with BioRender.com
Source publication
Women are significantly more likely to develop depression than men. Fluctuations in the ovarian estrogen hormone levels are closely linked with women's well-being. This narrative review discusses the available knowledge on the role of estrogen in modulating brain function and the correlation between changes in estrogen levels and the development of...
Contexts in source publication
Context 1
... exerts its action through estrogen receptors (ER) expressed in reproductive tissues, metabolic tissues (kidney, liver, and white adipose tissue), the lungs, bladder, and gastrointestinal tract [56]. In the brain, ERs are located in structures such as the PFC, Hip, Amy, and cerebellum (Cb), structures that are involved in learning and memory (Fig. 3) [57]. Two estrogen receptor subtypes (ERα and ERβ) are present in the human and rodent brains (Fig. 3) [58]. These receptors are located to the membrane, nuclear, and cytoplasmic and directly stimulate non-genomic and genomic pathways in neurons (Fig. 4) [59]. Nuclear receptors (ERα, ERβ) activated by steroid sex hormones, including ...
Context 2
... (kidney, liver, and white adipose tissue), the lungs, bladder, and gastrointestinal tract [56]. In the brain, ERs are located in structures such as the PFC, Hip, Amy, and cerebellum (Cb), structures that are involved in learning and memory (Fig. 3) [57]. Two estrogen receptor subtypes (ERα and ERβ) are present in the human and rodent brains (Fig. 3) [58]. These receptors are located to the membrane, nuclear, and cytoplasmic and directly stimulate non-genomic and genomic pathways in neurons (Fig. 4) [59]. Nuclear receptors (ERα, ERβ) activated by steroid sex hormones, including estradiol, show slower regulation. Genomic regulation triggers gene transcriptions over a more extended ...
Citations
... In addition to physical symptoms, menopause is associated with a wide range of psychological symptoms including anxiety, depression, and cognitive impairment [1]. The onset of depression is correlated with a decrease in ovarian function [2,3]. Although estrogen therapy manages menopausal symptoms and improves related anxiety, depression, and memory impairment [4], a large body of evidence suggests that long-term estrogen therapy increases the risk of breast and ovarian cancer, stroke, and cardiovascular disease [5]. ...
When postmenopausal women are under stress conditions, this exacerbates mood disorders and issues with neuroimmune systems. The porcine placenta is known to relieve menopausal depression in clinical trials, but its underlying mechanisms for depression and anti-inflammatory functions remain poorly defined. The present study was designed to examine the anti-inflammatory effects of enzymatic porcine placenta hydrolysate (EPPH) on LPS-induced levels of nitric oxide (NO), prostaglandin E2 (PGE2), corticosterone (CORT), and pro-inflammatory cytokine interleukin-1 beta (IL-1β) in RAW 264.7 macrophage cells. In addition, the neurite outgrowth of PC12 cells was evaluated to examine the effects of EPPH on neurite growth. To mimic the symptoms of women with menopause-related depression, a stressed ovariectomized (OVX) female mouse model was used to evaluate the antidepressant effects of EPPH. The female mice were randomly divided into five groups: (1) the sham-operated (Sham) group, (2) the OVX + repeated stress + saline-treated (OVX + ST) group, (3) the OVX + repeated stress + estradiol (0.2 mg/kg)-treated (positive control) group, (4) the OVX + repeated stress + EPPH (300 mg/kg)-treated (300) group, and (5) the OVX + repeated stress + EPPH (1500 mg/kg)-treated (1500) group. Female mice were OVX and repeatedly immobilization-stressed for 2 weeks (2 h/day). A tail suspension test was conducted on the 13th day, followed by the forced swimming test on the 14th day to assess the antidepressant effects of EPPH. After the behavioral tests, the levels of CORT, PGE2, and IL-1β were evaluated. In addition, c-Fos expression in the paraventricular nucleus (PVN) was evaluated using immunohistochemistry. The concentrations of NO, PGE2, and IL-1β stimulated by LPS were significantly reduced via the addition of EPPH to RAW 264.7 cells. EPPH significantly promoted neurite outgrowth in PC12 cells compared to that of the controls. In the tail suspension test, the duration of immobility was reduced in mice treated with EPPH 1500 compared to the OVX + ST group. The EPPH 1500 group had significantly decreased levels of c-Fos-positive neurons in the PVN and reduced levels of CORT and IL-1β in the serum of the Sham group. These results suggested that the high dose of EPPH administration induced the antidepressant-like effect in the ovariectomized mice with repeated stress via downregulating the levels of CORT, IL-1β, and PGE2 in the serum through reducing the expression of c-Fos in the PVN regions.
... E2 and P4 modulate brain activity by binding to their respective receptors. E2 receptors (ERs) and P4 receptors (PRs) are distributed throughout cortical and subcortical structures, with the most dense expression found in the prefrontal cortex, hippocampus, amygdala, and cerebellum (6)(7)(8)(9)(10). The distribution of ERs/PRs underscores the widespread influence that these hormones have on brain structure and function. ...
Background
Ovarian hormones exert direct and indirect influences on the brain; however, little is known about how these hormones impact causal brain connectivity. Studying the female brain at a single time point may be confounded by distinct hormone phases. Despite this, the menstrual cycle is often overlooked. The primary objective of this pilot study was to evaluate resting-state causal connectivity during the early follicular and mid-luteal menstrual phases corresponding to low vs high estradiol and progesterone, respectively.
Methods
Fourteen healthy control females ( M = 20.36 years, SD = 2.02) participated in this study. Participants were scheduled for two resting-state electroencephalography (EEG) scans during their monthly menstrual cycle. A saliva sample was also collected at each EEG session for hormone analyses. Causal connectivity was quantified using information flow rate of EEG source data. Demographic information, emotional empathy, and sleep quality were obtained from self-report questionnaires.
Results
Progesterone levels were significantly higher in the mid-luteal phase compared to the early follicular phase ( p = .041). We observed distinct patterns of causal connectivity along the menstrual cycle. Connectivity in the early follicular phase was centralized and shifted posteriorly during the mid-luteal phase. During the early follicular phase, the primary regions driving activity were the right central and left/right parietal regions, with the left central region being the predominant receiver of activity. During the mid-luteal phase, connections were primarily transmitted from the right side and the main receiver region was the left occipital region. Network topology during the mid-luteal phase was found to be significantly more assortative compared to the early follicular phase.
Conclusions
The observed difference in causal connectivity demonstrates how network dynamics reorganize as a function of menstrual phase and level of progesterone. In the mid-luteal phase, there was a strong shift for information flow to be directed at visual spatial processing and visual attention areas, whereas in the follicular phase, there was strong information flow primarily within the sensory-motor regions. The mid-luteal phase was significantly more assortative, suggesting greater network efficiency and resilience. These results contribute to the emerging literature on brain-hormone interactions.
... Our data clearly demonstrate that OVX decreases estradiol (estrogen) but increases oxidative stress; inflammatory cytokines; and AChE, MAO, and cortisol levels. The elevation in all these parameters except cortisol corresponds with previous studies [43][44][45][46][47]. However, the effect of OVX on cortisol is still controversial. ...
To increase the value of the by-products of the canned tuna industry, the memory enhancement effect and the possible mechanisms of omega-3-rich tuna oil in bilateral ovariectomized (OVX) rats were assessed. Female rats were orally given tuna oil at doses of 140, 200, and 250 mg/kg of body weight (BW) for 28 days before OVX and for 21 days continually after OVX. Memory performance was assessed every week, whereas the parameters regarding mechanisms of action were assessed at the end of the study. All doses of tuna oil enhanced memory, docosahexaenoic acid (DHA) levels, and superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities but decreased cortisol, acetylcholinesterase (AChE), malondialdehyde (MDA), and inflammatory cytokines such as tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). Medium and high doses of tuna oil suppressed monoamine oxidase (MAO) but increased eNOS activity. A high dose of tuna oil suppressed gamma-aminotransferase (GABA-T) but increased glutamic acid decarboxylase (GAD) and sirtuin-1. A medium dose of tuna oil decreased homocysteine (Hcys) and C-reactive protein. No change in telomere or estradiol was observed in this study. Our results suggest the memory-enhancing effect of tuna oil in an OVX rat model of menopause. The main mechanisms may involve a reduction in oxidative stress, inflammation, and neurotransmitter regulation.
... The vestibular system, comprising the inner ear and associated neural pathways, plays a crucial role in maintaining balance and spatial orientation [17,18]. Estrogen receptors within the vestibular system suggest a direct hormonal influence on its function [17][18][19]. Reduced estrogen levels during menopause may lead to changes in vestibular sensitivity and response, potentially contributing to the onset of vertigo [2]. ...
The onset of menopause, marked by hormonal fluctuations and a decline in estrogen levels, is suggested to be linked to increased susceptibility to vestibular disturbances. Estrogen, beyond its established association with reproductive physiology, plays modulatory roles in various physiological systems, including neurosensory function. The vestibular system, crucial for balance and spatial orientation, is influenced by hormonal changes during menopause, potentially contributing to the emergence of vertigo symptoms. This interplay between hormones and the vestibular system is a burgeoning area of research with clinical implications, offering insights into novel diagnostic and therapeutic approaches for managing postmenopausal women with vestibular disorders. The article reviews current scientific literature, delves into the hormonal intricacies of menopause, and investigates potential mechanisms underlying the connection between hormonal fluctuations and vertigo symptoms.
... E2 has been shown to modulate BDNF levels in hippocampal and cortical tissues and may exert neuroprotective effects in these brain structures by up-regulating the expression of this neurotrophin [52][53][54]. Consistent with previous rodent studies [55][56][57], our findings indicate that ovariectomized animals exhibit decreased BDNF levels in the hippocampus. ...
Menopause is the period in which women cease to produce the hormone estrogen, which can trigger physiological, cognitive, and behavioral changes. In this context, alternatives are needed that can reduce the effects provided by menopause, specifically in terms of cognitive and behavioral aspects. High-intensity interval training (HIIT) is an exercise protocol that has shown the potential to improve cognition by promoting an increase in antioxidant defenses and BDNF levels. Therefore, the aim of this study was to evaluate the effects of HIIT on behavior and hippocampal neurochemistry in ovariectomized adult rats. Four groups of rats were divided into: females without ovariectomy surgery and sedentary (SHAM-SED); females with ovariectomy surgery and sedentary (OVX-SED); females without ovariectomy surgery and trained (SHAM-HIIT); females with ovariectomy surgery and trained (OVX-HIIT). After the surgical procedure and the HIIT protocol, the animals underwent anxiety (elevated plus maze and open field) and memory (novel object recognition) tests. Corticosterone was measured in blood and BDNF levels and redox status were evaluated in the hippocampus. The OVX-SED group showed low BDNF levels and antioxidant enzymes, which may be linked to the observed memory impairments. The HIIT protocol (SHAM-HIIT and OVX-HIIT groups) increased the BDNF levels and antioxidant enzymes in the hippocampus, improving the animals' memory. However, HIIT also led to increased plasma corticosterone and anxiety-like behaviors. The ovariectomy procedure induced memory impairment probably due to reductions in hippocampal BDNF levels and redox imbalance. The HIIT protocol demonstrates promising results as an alternative to improve memory in ovariectomized rats.
... This suggests that the HIIT protocol may have strongly and positively influenced the antioxidant systems, leading to a substantial reduction in ROS levels in this brain structure. E 2 has been shown to modulate BDNF levels in hippocampal and cortical tissues and may exert neuroprotective effects in these brain structures by up-regulating the expression of this neurotrophin [52][53][54]. Consistent with previous rodent studies [55][56][57], our findings indicate that ovariectomized animals exhibit decreased BDNF levels in the hippocampus. ...
Menopause is the period in which women cease to produce the hormone estrogen, which can trigger physiological, cognitive, and behavioral changes. In this context, alternatives are needed that can reduce the effects provided by menopause, specifically in terms of cognitive and behavioral aspects. High-intensity interval training (HIIT) is an exercise protocol that has shown the potential to improve cognition by promoting an increase in antioxidant defenses and BDNF levels. Therefore, the aim of this study was to evaluate the effects of HIIT on behavior and hippocampal neurochemistry in ovariectomized adult rats. Four groups of rats were divided into: females without ovariectomy surgery and sedentary (SHAM-SED); females with ovariectomy surgery and sedentary (OVX-SED); females without ovariectomy surgery and trained (SHAM-HIIT); females with ovariectomy surgery and trained (OVX-HIIT). After the surgical procedure and the HIIT protocol, the animals underwent anxiety (elevated plus maze and open field) and memory (novel object recognition) tests. Corticosterone was measured in blood and BDNF levels and redox status were evaluated in the hippocampus. The OVX-SED group showed low BDNF levels and antioxidant enzymes, which may be linked to the observed memory impairments. The HIIT protocol (SHAM-HIIT and OVX-HIIT groups) increased the BDNF levels and antioxidant enzymes in the hippocampus, improving the animals' memory. However, HIIT also led to increased plasma corticosterone and anxiety-like behaviors. The ovariectomy procedure induced memory impairment probably due to reductions in hippocampal BDNF levels and redox imbalance. The HIIT protocol demonstrates promising results as an alternative to improve memory in ovariectomized rats.
Objective
The severity of menopausal symptoms, despite being triggered by hormonal imbalance, does not directly correspond to hormone levels in the blood; thus, the level of unpleasantness is assessed using subjective questionnaires in clinical practice. To provide better treatments, alternative objective assessments have been anticipated to support medical interviews and subjective assessments. This study aimed to develop a new objective measurement for assessing unpleasantness.
Methods
Fourteen participants with menopausal symptoms and two age-matched participants who visited our outpatient section were enrolled. Resting-state brain activity was measured using magnetoencephalography. The level of unpleasantness of menopausal symptoms was measured using the Kupperman Kohnenki Shogai Index. The blood level of follicle-stimulating hormone and luteinizing hormone were also measured. Correlation analyses were performed between the oscillatory power of brain activity, index score, and hormone levels.
Results
The level of unpleasantness of menopausal symptoms was positively correlated with high-frequency oscillatory powers in the parietal and bordering cortices (alpha; P = 0.016, beta; P = 0.015, low gamma; P = 0.010). The follicle-stimulating hormone blood level was correlated with high-frequency oscillatory powers in the dorsal part of the cortex (beta; P = 0.008, beta; P = 0.005, low gamma; P = 0.017), whereas luteinizing hormone blood level was not correlated.
Conclusion
Resting-state brain activity can serve as an objective measurement of unpleasantness associated with menopausal symptoms, which aids the selection of appropriate treatment and monitors its outcome.
