Figure - available from: The Scientific World Journal
This content is subject to copyright. Terms and conditions apply.
(a) Photomicrograph of 5-bromo-2-deoxyuridine (BrdU) immunopositive cells (new born neurons) in DG in the hippocampus of control and OVX mice with 17β-E2 or α-ZAL treatment. Fewer BrdU-labeled cells were observed in OVX mice compared to control. 17β-E2 and α-ZAL-treated mice expressed higher BrdU⁺ cells compared to OVX animal. Magnification ×40. (b) Quantification of BrdU immunolabeling cells in DG. n = 4 in each group and the result indicated at least three independent experiments in each animal. P * * < 0.01 versus control group; P # # < 0.01 versus OVX group.
Source publication
Estrogen is known to provide robust protection of memory in postmenopausal women, but the fact that estrogen may increase the incidence of uterine and breast tumors has undoubtedly limited the clinical use of estrogen. In the present study, the effect of α-zearalanol (α-ZAL), a plant-derived phytoestrogen with low side-effect on uterine and breast,...
Similar publications
Background: Studies have demonstrated that estradiol influences cognitive functions. Phytoestrogens and many other estrogen-like compounds in plants have beneficial effects on cognitive performance in postmenopausal women. However, there is no evident report of fenugreek and choline-Docosahexaenoic Acid (DHA) on cognition in ovariectomized rats. Ai...
Citations
... On the other hand, ZEA exerted no effect on estrogen biosynthesis in glioblastoma cells (Wang et al. 2014). In a few reports, administration of ZEA or its derivatives led to positive outcome on memory impairment and adult neurogenesis (Dong et al. 2014) or was neuroprotective by counterbalancing the effects of ovariectomy or -amyloid (25-35) induced oxidative / ER stress (Dong et al. 2006(Dong et al. , 2007(Dong et al. , 2017. ...
Fumonisin B1, deoxynivalenol (DON) and zearalenone (ZEA) are toxic secondary metabolites produced by Fusarium molds. These mycotoxins are common food and feed pollutants and represent a risk for human and animal health. Although the mycotoxins produced by this genus can cross the blood-brain-barrier (BBB) in many species, their effect on neuronal function remains unclear. We investigated cell viability effects of these toxins on specified neural cell types, including mouse primary neuronal, astroglial and mixed cell cultures 24 or 48 hours after mycotoxin administration. Cell viability assay revealed that DON decreased cell viability in a dose-dependent manner, independently from the culture's type. Fumonisin B1 increased cell viability significantly on astroglial and mixed cell cultures in lower doses, while it exerted a highly toxic effect in 50 μM. ZEA had significant effects on all culture type in 10 nM by increasing the cell viability. Since ZEA is a mycoestrogen, we analyzed the effects of ZEA on the expression of estrogen receptor isotypes ERα and ERβ and mitochondrial voltage-dependent anion channel (VDAC1) by qRT-PCR. In neuronal and mixed cultures, ZEA administration decreased ERα expression, while in astroglial cultures, it induced the opposite effect. ERβ and VDAC1 expression was not altered by ZEA in either culture types. ZEA also affected the firing pattern of neurons by enhancing the burst frequency. Our results demonstrate that Fusarium mycotoxins are acting on a cell specific manner in the brain tissue.
... Stress is known to inhibit stem/progenitor cell proliferation [10][11][12][13] in the dentate gyrus and the Subventricular zone [14][15][16]. Previous studies show that sex hormones increase stem/progenitor cell proliferation, with estrogen [17][18][19], prolactin [20][21][22] and testosterone [23,24]. We know that certain growth factors must be present for stem/progenitor cell proliferation to increase, including Brain-Derived Neurotrophic Factor (BDNF) [25][26][27], and that in general, stem/progenitor cell proliferation decreases in aged rats [6]. ...
... While estrone and estriol are less bioactive than estradiol, their effects on dendritic spines require future investigation, especially with regards to pregnancy (when circulating estriol levels increase greatly as a result of placental production [50]) and post-menopause (when 17β-estradiol levels decline more so than estrone levels leading to estrone becoming the most abundant of the estrogens [51]), periods in which hippocampal dendritic spine numbers are increased [52,53] and decreased (typically investigated via ovariectomy) [32,[54][55][56], respectively. It should further be mentioned that this review does not cover the effects of phytoestrogens (weak estrogens found in plants) or endocrine disruptors such as bisphenol-A on dendritic spine density or neurogenesis; however, there is emerging evidence that phytoestrogens may affect these types of hippocampal plasticity [57][58][59][60][61][62][63]. ...
It is well established that estrogens affect neuroplasticity in a number of brain regions. In particular, estrogens modulate and mediate spine and synapse formation as well as neurogenesis in the hippocampal formation. In this review, we discuss current research exploring the effects of estrogens on dendritic spine plasticity and neurogenesis with a focus on the modulating factors of sex, age, and pregnancy. Hormone levels, including those of estrogens, fluctuate widely across the lifespan from early life to puberty, through adulthood and into old age, as well as with pregnancy and parturition. Dendritic spine formation and modulation are altered both by rapid (likely non-genomic) and classical (genomic) actions of estrogens and have been suggested to play a role in the effects of estrogens on learning and memory. Neurogenesis in the hippocampus is influenced by age, the estrous cycle, pregnancy, and parity in female rodents. Furthermore, sex differences exist in hippocampal cellular and molecular responses to estrogens and are briefly discussed throughout. Understanding how structural plasticity in the hippocampus is affected by estrogens and how these effects can influence function and be influenced by other factors, such as experience and sex, is critical and can inform future treatments in conditions involving the hippocampus.
... As a consequence, many women are searching for safer alternative treatments to manage their menopausal symptoms. To avoid these side effects, phytoestrogens which are estrogen-like substance derived from foods and plants, such as extracts from soybean and traditional Chinese medicine, have become a new source of estrogen [5]. These phytoestrogens do not simply mimic the effects of human sex hormones but also exhibit similar and divergent actions [6]. ...
A Chinese herbal preparation, QingYan formula (QYF), has been used clinically for kidney-invigorating. However, no evidence base links QYF to estrogen replacement therapy. In this study, the estrogenic effects of QingYan formula 70% ethanol extract (QYFE) were investigated in immature mice. Immature mice were treated with QYFE at doses of 1, 2, and 4g/kg for 7 days. QYFE treatments promoted vaginal cornification and prolonged the estrus status of the immature mice, promoted the growth and development of uterus and vagina, upregulated ER α and ER β expression at protein level in uterus and vagina, increased the level of estradiol (E 2 ), and decreased concentration of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) in serum. This study demonstrated that QYFE exerts estrogenic effects by stimulating biosynthesis of estrogen and increasing estrogen receptors (ERs) in target tissues and provided an evidence base for QYFE treatment instead of estrogen replacement therapy.
... This may be partially due to the reduction of neurons in specific brain regions such as neurons in CA1, dorsal hippocampus and medial prefrontal cortex [30,37]. In addition, previous studies showed that ovariectomy impairs learning and memory in rodents [11]. In line with these studies, our results showed that ovariectomy impaired the novelty-induced exploratory behaviors in mice. ...
The aim of this study was to evaluate the anti-diabetic drug metformin (Met) effects on the anxiety and cognitive impairment in ovariectomized mice. Thirty-two female adult mice were distributed into four groups: control, sham ovariectomy, ovariectomy + Met 7 mg/kg and ovariectomy + Met 15 mg/kg. The vaginal cytology was used to confirm the ovariectomy surgery. Anxiety was monitored using elevated plus maze test and cognitive function was assessed by novel object recognition task. Animal's brains were analyzed for the brain-derived neurotrophic factor (BDNF). Our results demonstrated that ovariectomy caused cognitive impairments and anxiety, as well as decreased BDNF levels. Moreover, administration of Met improves ovariectomy-related disorders such as cognitive impairments and anxiety, as well as increased BDNF levels. The results of the present study suggest that Met could be used as a novel therapeutic strategy for the treatment of ovariectomy-related conditions.
... e l s e v i e r . c o m / l o c a t e / t a a p genistein, found in soy ( Gong et al., 2014;Li et al., 2013;Nikov et al., 2000); the flavones apigenin found in parsley or chamomile ( Li et al., 2013); and liquiritigenin found in licorice root ( Gong et al., 2014). An- other chemical class of phytoestrogens is represented by coumestrol, a coumestan also found in soy and alfalfa (Li et al., 2013;Nikov et al., 2000). ...
... e l s e v i e r . c o m / l o c a t e / t a a p genistein, found in soy ( Gong et al., 2014;Li et al., 2013;Nikov et al., 2000); the flavones apigenin found in parsley or chamomile ( Li et al., 2013); and liquiritigenin found in licorice root ( Gong et al., 2014). An- other chemical class of phytoestrogens is represented by coumestrol, a coumestan also found in soy and alfalfa (Li et al., 2013;Nikov et al., 2000). ...
... For instance, the derivative ?-zearalenol, resulting from the hy- droxylation of zearalenone by hydroxysteroid dehydrogenases (HSDs), was at least in vitro as strong as E2 (Le Guevel and Pakdel, 2001;Shier et al., 2001). The metabolite ?-zearalanol was shown to improve hippo- campal neurogenesis in ovariectomized mice, at the same concentration that E2 ( Dong et al., 2014). In our case, zearalenone or its metabolite was accompanied by harmful effects (proliferation of breast cancer cells and an absence of an effect on NGF-induced neuritogenesis). ...
Estrogen receptors (ERs) α and β are distributed in most tissues of women and men. ERs are bound by estradiol (E2), a natural hormone, and mediate the pleiotropic and tissue-specific effects of E2, such as proliferation of breast epithelial cells or protection and differentiation of neuronal cells. Numerous environmental molecules, called endocrine disrupting compounds, also interact with ERs. Phytoestrogens belong to this large family and are considered potent therapeutic molecules that act through their selective estrogen receptor modulator (SERM) activity. Using breast cancer cell lines as a model of estrogen-dependent proliferation and a stably ER-expressing PC12 cell line as a model of neuronal differentiating cells, we studied the SERM activity of major dietary compounds, such as apigenin, liquiritigenin, daidzein, genistein, coumestrol, resveratrol and zearalenone. The ability of these compounds to induce ER-transactivation and breast cancer cell proliferation and enhance Nerve Growth Factor (NGF) -induced neuritogenesis was assessed. Surprisingly, although all compounds were able to activate the ER through an estrogen responsive element reporter gene, they showed differential activity toward proliferation or differentiation. Apigenin and resveratrol showed a partial or no proliferative effect on breast cancer cells but fully contributed to the neuritogenesis effect of NGF. However, daidzein and zearalenone showed full effects on cellular proliferation but did not induce cellular differentiation. In summary, our results suggest that the therapeutic potential of phytoestrogens can diverge depending on the molecule and the phenotype considered. Hence, apigenin and resveratrol might be used in the development of therapeutics for breast cancer and brain diseases.
... Rodent studies have shown adult DG neurogene- sis is important in mediating hippocampal-dependent learning and memory, and the reduction in neurogenesis is a causative factor of memory impairments [127][128][129]. Couple of studies reported that phytoestrogens plays important role in neurogenesis via facilitating axonal sprouting, improving synaptic transmission, and enhance- ment of neurotrophic factors [130,131]. A study by Dong et al. [130] reported that phytoestrogens, -Zearalanol, improves mem- ory impairment and hippocampal neurogenesis in ovariectomized mice. ...
Menopause jeopardizes the integrity of brain and makes it vulnerable to various diseases, both of psychiatric and degenerative nature. Exogenous estrogen supplementation confers neuroprotection but the results of Women's Health Initiative (WHI), Million Women Study (MWS) and incidence of endometrial cancer, breast cancer and venous thromboembolism reported with estrogen use have engendered doubts over its clinical translation for postmenopausal neurological disorders. Scientific community and general public have started recognizing the protective potential of phytochemicals in climacteric medicine. These phytochemicals are plant-derived, non-steroidal bioactive estrogenic compounds. Emerging preclinical studies have suggested that these phytochemicals display potential benefits in mitigating postmenopausal depression, anxiety, cerebral ischemia and cognitive dysfunction. Thus, the aim of present review is: a) to give an overview of neuroprotective action of estrogen, b) to address the chemical and pharmacological features of various classes of phytoestrogens, and c) to present preclinical and clinical evidence of effect of phytoestrogens on climacteric neurobiology with their possible mechanisms of action.
... Another phytoestrogen, -zearalanol ( -ZAL), has been used as a safe alternative for estrogen, due to reduced side effects on the uterus and breast. Studies showed that both -ZAL and 17 -E2 improved neurogenesis and learning and memory deficits [149]. ...
Although the literature reports a higher incidence of anxiety disorders in women, the majority of basic research has focused on male rodents, thus resulting in a lack of knowledge on the neurobiology of anxiety in females. Bridging this gap is crucial for the design of effective translational interventions in women. One of the key brain mechanisms likely to regulate anxious behavior is adult hippocampal neurogenesis (AHN). This review paper aims to discuss the evidence on the differences between male and female rodents with regard to anxiety-related behavior and physiology, with a special focus on AHN. The differences between male and female physiologies are greatly influenced by hormonal differences. Gonadal hormones and their fluctuations during the estrous cycle have often been identified as agents responsible for sexual dimorphism in behavior and AHN. During sexual maturity, hormone levels fluctuate cyclically in females more than in males, increasing the stress response and the susceptibility to anxiety. It is therefore of great importance that future research investigates anxiety and other neurophysiological aspects in the female model, so that results can be more accurately applicable to the female population.
Zearalenone (ZEA) is a mycotoxin produced by the fungi of Fusarium genera, which contaminates the cereals and food stuffs worldwide. Fusarium mycotoxins are considered as important metabolites related to animal and human health. Evidences indicate that ZEA has been found to be present in different food stuffs from developed countries like USA, Canada, France, Germany, Japan, etc. and developing nations like Egypt, Thailand, Iran, Croatia, Philippines, etc. The toxicokinetic studies reveal that following oral exposure of ZEA, the compound is absorbed through gastrointestinal tract (GIT), gets metabolized and distributed to different body parts. ZEA has been shown to cause reproductive disorders in laboratory animals. Although the toxicity of ZEA in humans have not been conclusively established nonetheless, limited evidences indicate that ZEA can cause hyper estrogenic syndrome. Though, ZEA causes low acute toxicity, but reports are available confirming the systemic toxicity caused by ZEA. There is no review available that addresses the occurrence, systemic toxicity and the probable mechanisms of ZEA toxicity. This review shall address the world-wide occurrence and in vivo & in vitro toxicity studies of ZEA over the past 20 years. The review shall also discuss the toxicokinetics of ZEA and metabolites; illustrates the systemic toxicity and probable mechanisms of action leading to the risk associated with ZEA.
Aims
Cerebral ischemia reperfusion (I/R) is a neurovascular disease leading to cerebral damage. It was found that postmenopausal women are liable to more dangerous effects than men at same age in stroke. The objective of this study is to investigate the neuroprotective effect of zeranol against cerebral ischemia reperfusion in ovariectomized rats.
Main methods
36 female wistar rats divided in to 3 groups: sham group, I/R group (where I/R was induced 7 weeks after ovariectomy), zeranol group (0.5 mg/kg every 3 days for 5 weeks before I/R). Cerebral ischemia reperfusion (I/R) was performed by bilateral common carotid artery occlusion then de-ligated to restore blood flow. After 24 h of reperfusion, rats performed cylinder test to evaluate behavioral dysfunction followed by decapitation. Brain tissues were collected for biochemical measures such as oxidative stress marker malondialdehyde, antioxidant markers reduced glutathione, inflammatory markers (interleukin-1 beta, tumor necrosis factor alpha, and inducible nitric oxide synthase), matrix metalloproteinase-9, adenosine triphosphate, brain derived neurotrophic factor, glucose transporter-3, phosphorylated c-AMP response element binding protein and finally nissl staining for histopathological examination.
Key findings
The zeranol administered group showed a reversal of neuronal damage caused by ischemia evidenced by the decrease in MDA, IL-1β, TNF-α, and MMP-9 levels, increase GSH, and ATP levels, decrease expression of iNOS in both regions cortex and hippocampus, increase protein level of p-CREB, GLUT-3 and BDNF, increase number of intact neuron cells in both regions and attenuated histological changes in both cortex and hippocampus regions.
Significance
Zeranol has neuroprotective potential against cerebral ischemia reperfusion in ovariectomized rats.
