Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Estrogen has received considerable attention as a potential therapeutic agent against various forms of neurodegenerative diseases including stroke. Experimental data in animal models of stroke have provided exhaustive evidence of the neuroprotective properties of this steroid hormone. Our laboratory in particular has demonstrated that acute estrogen treatment in male rats significantly reduced (approximately 50%) ischemic cell death within 4 h following permanent occlusion of the middle cerebral artery occlusion (MCAO). However, the cellular and molecular mechanisms implicated in the protective actions of estrogen in this experimental model have yet to be elucidated. Accumulating evidence suggests that in various in vivo and in vitro models, estrogen can be pro-apoptotic and that this effect may be mediated by an estrogen-induced up-regulation of the Fas/FasL system and the subsequent activation of caspase-12. We therefore hypothesized that under ischemic conditions following MCAO, estrogen would up-regulate protective endoplasmic reticulum (ER) stress pathways leading to caspase-12 activation, thus limiting infarct volume. Our results showed that estrogen significantly increased activated caspase-12 at 2, 3 and 4 h post-MCAO. Immunostaining of brain sections showed a significantly higher number of terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labeling positive cells in estrogen-treated animals at 4 h, but not at 2 h, post-MCAO. These findings correlate with previous observations that differences in infarct volume between saline and estrogen-treated animals are not seen until 3 and 4 h post-MCAO. A decrease in m-calpain expression was observed in the infarct region only at 4 h post-MCAO following estrogen pre-treatment, suggesting m-calpain may not be involved in regulating estrogen-induced caspase-12 activation. Based on these cellular changes correlated to estrogen pretreatment, we conclude that estrogen may up-regulate ER-specific apoptotic pathways, thus limiting the extent of necrotic cell death which is responsible for the spreading depression and growth of the infarct volume following MCAO.
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PMID:Estrogen limits ischemic cell death by modulating caspase-12-mediated apoptotic pathways following middle cerebral artery occlusion. 1743 54

Sleep difficulty is one of the hallmarks of menopause. Following recent studies showing no cardiac benefit and increased breast cancer, the question of indications for hormonal therapy has become even more pertinent. Three sets of sleep disorders are associated with menopause: insomnia/depression, sleep disordered breathing and fibromyalgia. The primary predictor of disturbed sleep architecture is the presence of vasomotor symptoms. This subset of women has lower sleep efficiency and more sleep complaints. The same group is at higher risk of insomnia and depression. The "domino theory" of sleep disruption leading to insomnia followed by depression has the most scientific support. Estrogen itself may also have an antidepressant as well as a direct sleep effect. Treatment of insomnia in responsive individuals may be a major remaining indication for hormone therapy. Sleep disordered breathing (SDB) increases markedly at menopause for reasons that include both weight gain and unclear hormonal mechanisms. Due to the general under-recognition of SDB, health care providers should not assume sleep complaints are due to vasomotor related insomnia/depression without considering SDB. Fibromyalgia has gender, age and probably hormonal associations. Sleep complaints are almost universal in FM. There are associated polysomnogram (PSG) findings. FM patients have increased central nervous system levels of the nociceptive neuropeptide substance P (SP) and lower serotonin levels resulting in a lower pain threshold to normal stimuli. High SP and low serotonin have significant potential to affect sleep and mood. Treatment of sleep itself seems to improve, if not resolve FM. Menopausal sleep disruption can exacerbate other pre-existing sleep disorders including RLS and circadian disorders.
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PMID:Menopause related sleep disorders. 1756 92

During the past decade there has been a substantial advance in our understanding of estrogen signaling both from a clinical as well as a preclinical perspective. Estrogen signaling is a balance between two opposing forces in the form of two distinct receptors (ER alpha and ER beta) and their splice variants. The prospect that these two pathways can be selectively stimulated or inhibited with subtype-selective drugs constitutes new and promising therapeutic opportunities in clinical areas as diverse as hormone replacement, autoimmune diseases, prostate and breast cancer, and depression. Molecular biological, biochemical, and structural studies have generated information which is invaluable for the development of more selective and effective ER ligands. We have also become aware that ERs do not function by themselves but require a number of coregulatory proteins whose cell-specific expression explains some of the distinct cellular actions of estrogen. Estrogen is an important morphogen, and many of its proliferative effects on the epithelial compartment of glands are mediated by growth factors secreted from the stromal compartment. Thus understanding the cross-talk between growth factor and estrogen signaling is essential for understanding both normal and malignant growth. In this review we focus on several of the interesting recent discoveries concerning estrogen receptors, on estrogen as a morphogen, and on the molecular mechanisms of anti-estrogen signaling.
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PMID:Estrogen receptors: how do they signal and what are their targets. 1761 92

Estrogen has its receptor in the brain and affects the nervous system in various ways. To date, it has been paid attention whether the cognitive function and the risk of depression change due to estrogen deficiency and also whether these changes respond to hormone replacement therapy (HRT). The increase in female life expectancy accelerates the prevalence of dementia like Alzheimer Disease, so the efficacy of HRT in the cognitive function got the public attention. On the contrary, a series of large-scale randomized controlled trials (Women's Health Initiative Memory Study: WHIMS) in aged 65 years or older women showed HRT increases the risk of dementia. However, certain studies indicate HRT may have beneficial effect on dementia when being started earlier. Therefore direct application of the result of WHIMS for the climacteric women is still controversial.
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PMID:[Hormone replacement Up-to-date. Hormone replacement therapy and brain function]. 1776 23

Estrogen modulates memory-related synaptic plasticity not only slowly but also rapidly in the hippocampus. However, molecular mechanisms of the rapid action are yet largely unknown. We here describe rapid modulation of representative synaptic plasticity, i.e., long-term depression (LTD), long-term potentiation (LTP) and spinogenesis, by 17beta-estradiol, selective estrogen agonists as well as endocrine disrupters. The authors demonstrated that 1-10 nM estradiol induced rapid enhancement of LTD within 1 h in not only CA1 but also CA3 and dentate gyrus (DG). On the other hand, the modulation of LTP by estradiol was not statistically significant. The total density of spines was increased in CA1 pyramidal neurons, within 2 h after application of estradiol. The total density of thorns (postsynaptic spine-like structure) was, however, decreased by estradiol in CA3 pyramidal neurons. Both the increase of spines in CA1 and the decrease of thorns in CA3 were completely suppressed by Erk MAP kinase inhibitor. Only ERalpha agonist PPT induced the same enhancement/suppression effect as estradiol on both LTD and spinogenesis in CA1 and CA3. ERbeta agonist DPN induced completely different results. ERalpha localized in spines and presynapses of principal glutamatergic neurons in CA1, CA3 and DG. The same ERalpha was also located in nuclei and cytoplasm. Identification of ERalpha was successfully performed using purified RC-19 antibody. Non-purified ERalpha antisera, however, reacted significantly with unknown proteins, resulting in wrong immunostaining different from real ERalpha distribution. An issue of 'endocrine disrupters' (1-100 nM low dose of environmental chemicals), which are artificial xenoestrogenic or anti-xenoestrogenic substances, has emerged as a social and environmental problem. Endocrine disrupters were found to significantly modulate LTD and spinogenesis. Bisphenol A (BPA) and diethylstilbestrol (DES) enhanced LTD in CA1 and CA3. The total spine density was significantly increased by BPA and DES in CA1. Most probable receptors for BPA and DES may be Ralpha; however, other receptors might also be involved.
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PMID:Rapid modulation of synaptic plasticity by estrogens as well as endocrine disrupters in hippocampal neurons. 1782 75

Although several studies have shown that the administration of 17beta-estradiol (estrogen) is cardioprotective to ischemia-reperfusion (I/R), the molecular mechanisms are largely unknown. Therefore, we investigated the effects of estrogen on myocardial I/R injury in rat that were sham operated (Sham), ovariectomized (OVX), or ovariectomized and then given estrogen supplementation (OE). Langendorff-perfused rat hearts were subjected to I/R stimuli and the effects of estrogen were examined on cardiac performance. Additionally, we examined the mechanism of estrogen-mediated inhibition of apoptosis. Depression in cardiac contractile function and an increment of calpain activity were observed during I/R in the OVX rats. Estrogen replacement recovered cardiac contractile function and attenuated calpain activity, Bid cleavage, and caspases activities. Through in vitro assay using cardiomyocytes, we demonstrated that addition of H2O2 (100 microM) significantly increased calpain activity, which was attenuated by estrogen. Moreover, calpain activity was inhibited by calpain inhibitors such as ALLN or leupeptin, but not by caspase-8 inhibitor peptide. These results suggest that estrogen protects the heart against I/R injury through the decrease of calpain activity, Bid cleavage and caspase-8 activity. These apoptotic mechanisms may play a critical role on I/R-associated cardiac damage.
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PMID:Estrogen attenuates cardiac ischemia-reperfusion injury via inhibition of calpain-mediated bid cleavage. 1803 1

The menopausal transition is a time of risk for mood change ranging from distress to minor depression to major depressive disorder in a vulnerable subpopulation of women in the menopausal transition. Somatic symptoms have been implicated as a risk factor for mood problems, although these mood problems have also been shown to occur independently of somatic symptoms. Mood problems have been found to increase in those with a history of mood continuum disorders, but can also occur de novo as a consequence of the transition. Stress has been implicated in the etiology and the exacerbation of these mood problems. Estrogen and add-back testosterone have both been shown to positively affect mood and well-being. In most cases, the period of vulnerability to mood problems subsides when the woman's hormonal levels stabilize and she enters full menopause.
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PMID:Neurobehavioral impact of menopause on mood. 1803 71

Trauma-hemorrhage leads to prolonged immune suppression, sepsis, and multiple organ failure. The condition affects all compartments of the immune system, and extensive studies have been carried out elucidating the immunological events following trauma-hemorrhage. The immune alteration observed following trauma-hemorrhage is gender dependent in both animal models and humans, though some studies in humans are contradictory. Within 30 min after trauma-hemorrhage, splenic and peritoneal macrophages, as well as T-cell function, are depressed in male animals, but not in proestrus females. Studies have also shown that the mortality [corrected] rate and the induction of subsequent sepsis following trauma-hemorrhage are significantly higher in males and ovariectomized females compared with proestrus females. These and other investigations show that sex hormones form the basis of this gender dichotomy, and administration of estrogen can ameliorate the immune depression and increase the survival rate after trauma-hemorrhage. This review specifically elaborates the studies carried out thus far demonstrating immunological alteration after trauma-hemorrhage and its modulation by estrogen. Also, estrogen was shown to produce its salutary effects through nuclear as well as extranuclear receptors. Estrogen rapidly activates several protein kinases and phosphatases, as well as the release of calcium in different cell types. The results of the studies exemplify the promise of estrogen as a therapeutic adjunct in treating adverse pathophysiological conditions following trauma-hemorrhage.
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PMID:Estrogen: a novel therapeutic adjunct for the treatment of trauma-hemorrhage-induced immunological alterations. 1823 43

Drospirenone 3 mg/ethinyl estradiol 20 microg (24/4) is a new unique oral contraceptive formulation that combines in a novel dosing regimen the lowest dosage of ethinyl estradiol commonly used today with drospirenone, an innovative progestin. Drospirenone is a compound closely resembling progesterone, but with the antimineralocorticoid and antiandrogenic properties of a related therapeutic agent, the diuretic, antihypertensive and androgen receptor antagonist, 17alpha-spironolactone. The prolongation of hormonally active pills in the monthly drospirenone/ethinyl estradiol cycle from 21 days to 24 days, followed by 4 days of inactive pills, is an interesting variant of the recently developed extended pill regimens (1). Recent contraceptive research has focused on improving side effect profiles and providing noncontraceptive health and lifestyle advantages. Many of these benefits are now supported with evidence-based medicine (2). Most available oral contraceptives improve cycle regularity, menstrual pain, excessive menstrual flow and acne. However, weight gain, bloating, food cravings, breast tenderness and mood alterations (especially irritability and depression and the complex of affective, behavioral and somatic symptoms of premenstrual syndrome [PMS] and the severe form of PMS, premenstrual dysphoric disorder [PMDD]) are not generally improved with the traditional oral contraceptive formulations (3). Drospirenone/ethinyl estradiol 24/4 is currently the only hormonally based contraceptive regimen with large, randomized, controlled trials demonstrating efficacy for PMDD. It has received U.S. Food and Drug Administration (FDA) indications not only for the prevention of pregnancy but also for PMDD and for moderate acne vulgaris in women who choose oral contraception for birth control (4, 5).
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PMID:Drospirenone/ethinyl estradiol. 1838 90

Estrogen is thought to be involved in the pathophysiology of depression and suicidal behaviors. We studied gene variants of estrogen receptor alpha (rs827421, rs1913474, rs1801132, rs722207, rs974276 and rs910416) in 167 German suicide attempters (affective spectrum n=107, schizophrenia spectrum n=35, borderline personality disorder n=25), 92 German individuals who committed suicide and 312 German healthy subjects. Single markers and haplotype analysis in relation to suicidal behaviors (suicide attempters/completers) did not reveal any significant association. These were also not associated with related features, such as violence or impulsivity of suicide attempt, State-Trait Anger Expression Inventory (STAXI) and Questionnaire for Measuring Factors of Aggression (FAF) scores. In conclusion, our study does not support the hypothesis that estrogen receptor alpha gene variants are major contributors to suicide or to anger- or aggression-related behaviors.
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PMID:Estrogen receptor gene 1 variants are not associated with suicidal behavior. 1851 Nov 31


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