Aged Ovariectomized Rats Research Articles

Increasing hippocampal estrogen receptor alpha levels via viral vectors increases MAP kinase activation and enhances memory in aging rats in the absence of ovarian estrogens.

We previously demonstrated that aged ovariectomized rats that had received prior estradiol treatment in middle-age exhibited increased levels of estrogen receptor alpha (ERα) in the hippocampus as well as enhanced hippocampal dependent memory as compared to aged rats that had not received mid-life estradiol treatment. These effects persisted long after the estradiol treatment had been terminated. The goal of the current experiment was to determine if increased expression of ERα in the hippocampus, in the absence of exogenously administered estrogens, can impact the hippocampus and cognitive function in aging ovariectomized rats. Middle-aged rats were trained for 24 days on an eight-arm radial maze spatial memory task. All rats were then ovariectomized. Forty days later, rats received either lentiviral delivery to the hippocampus of the gene encoding ERα (lenti-ERα) or a control virus. Rats were tested on delay trials in the radial-maze in which delays of varying lengths were imposed between the fourth and fifth arm choices. Following behavior testing, hippocampi were immunostained using western blotting for ERα, the ERα-regulated protein choline acetyltransferase, and phosphorylation of the ERα-regulated kinases, ERK/MAPK and Akt. Results revealed that aging ovariectomized rats that received delivery of lenti-ERα to the hippocampus exhibited enhanced spatial memory as indicated by increased arm-choice accuracy across delays as compared to ovariectomized rats that received control virus. Western blot data revealed that lenti-ERα delivery significantly increased levels of ERα and phosphorylated ERK/MAPK and had no impact on levels of ChAT or phosphorylation of Akt. Results indicate that increasing hippocampal levels of ERα in aging females in the absence of ovarian or exogenously administered estrogens leads to increases in phosphorylation of ERK/MAPK as well as in enhanced memory.

Abstract 342: Increased Mitochondrial Permeability Transition Pore Opening Dominates Ischemia-Reperfusion Injury in the Aged Female Rat Heart

Background: Cardiovascular disease remains the leading cause of death in older post-menopausal women. Ischemia/Reperfusion (I/R) injury triggers mitochondrial calcium (Ca 2+ ) overload inducing mitochondrial permeability transition pore (MPTP) opening, mitochondrial dysfunction, and cell death potentially by necrosis, apoptosis, and/or autophagy. Purpose: We sought to determine if age-associated estrogen deficiency increases mitochondrial Ca 2+ sensitivity, providing a possible mechanism for increased vulnerability to I/R injury in older women. Methods: Mitochondrial respiration (MR) was assessed in isolated mitochondria from ventricles of adult (6 mo; n=15) and aged (24 mo; n=18) ovary-intact or ovariectomized (OVX) female F344 rats. MR at complexes I and II was compared in the absence (State 2) and presence (State 3) of ADP to calculate respiratory control index (RCI; state3/state 2). Reduced RCI following Ca 2+ addition was used to assess Ca 2+ sensitivity, while mitochondrial Ca 2+ retention capacity was measured to quantify MPTP opening (CRC; n=4-5/group) prior to and following coronary artery ligation (55 min I and 6 hr R). Apoptosis was examined using DNA laddering and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL). Markers of autophagy were evaluated by western blotting and mitochondrial morphology through electron microscopy (EM). Results: Significant age-dependent decreases in RCI for complex I (12%) and complex II (8%) were observed in the absence of Ca 2+ , and correlated with increased necrosis in aged hearts revealed by triphenyltetrazolium chloride (TTC) staining (p < 0.05). Ca 2+ exposure decreased MR (18-30%; p < 0.05) in Complex I of aged and OVX mitochondria vs adults. Furthermore, CRC worsened with age requiring less Ca 2+ to open the MPTP. Reduced DNA laddering and TUNEL staining combined with increased beclin-1 and cathepsinD expression in aged vs. adult further support a dominant role for necrosis over apoptosis underlying cell death in aged females (n=4-5/group). EM revealed morphological alterations with age and OVX. Conclusion: Decreased MR and increased MPTP opening with aging are likely causal in necrotic cell death mechanisms associated with I/R injury observed in post-menopausal women.

Effect of raloxifene and atorvastatin in atherosclerotic process in ovariectomized rats

The goal of this study was to investigate the combined effects of raloxifene and atorvastatin in aged ovariectomized rats during endothelial dysfunction and atherosclerotic process. This study was conducted on 28 Wistar albino female rats randomly divided into four groups. All groups were ovariectomized and one group was kept as the control group (OVX). For four weeks, the remaining three groups were treated with the statin atorvastatin (OVX+AV), the selective estrogen receptor modulator raloxifene (OVX+RL), and both atorvastatin and raloxifene (OVX+RL+AV), respectively. At the end of the treatment period, all rats were sacrificed and thoracic aortas excised, and endothelial cells were immunohistochemically stained for markers in the atherosclerotic process, such as inducible nitric oxide synthase (iNOS), endothelial nitric oxide synthase (eNOS), endothelin-1 (ET-1), monocyte chemotactic protein-1 (MCP-1), and tumor necrosis factor alpha (TNF-α). Compared to the ovariectomized group, the iNOS level was significantly increased in the OVX+RL group (P=0.002), but contrarily decreased in the groups OVX+AV (P=0.002) and OVX+RL+AV (P=0.002). eNOS levels in the groups OVX+AV (P=0.002) and OVX+RL+AV (P=0.002) were significantly lower than that in the OVX group. When compared to the OVX group, significant reductions in ET-1 and TNF-α levels were found in all treatment groups. A significant decrement in MCP-1 level was found in the OVX+AV group (P=0.002). In aged ovariectomized rats, the administration of both raloxifene and atorvastatin significantly decreased the levels of ET-1 and TNF-α on endothelial cells. Combined treatment with these drugs shortly after menopause might play a potential preventive role in the early stages of atherosclerosis development.

Galanthamine plus estradiol treatment enhances cognitive performance in aged ovariectomized rats

We hypothesize that beneficial effects of estradiol on cognitive performance diminish with age and time following menopause due to a progressive decline in basal forebrain cholinergic function. This study tested whether galanthamine, a cholinesterase inhibitor used to treat memory impairment associated with Alzheimer's disease, could enhance or restore estradiol effects on cognitive performance in aged rats that had been ovariectomized in middle-age. Rats were ovariectomized at 16–17months of age. At 21–22months of age rats began receiving daily injections of galanthamine (5mg/day) or vehicle. After one week, half of each group also received 17ß-estradiol administered subcutaneously. Rats were then trained on a delayed matching to position (DMP) T-maze task, followed by an operant stimulus discrimination/reversal learning task. Treatment with galanthamine+estradiol significantly enhanced the rate of DMP acquisition and improved short-term delay-dependent spatial memory performance. Treatment with galanthamine or estradiol alone was without significant effect. Effects were task-specific in that galanthamine+estradiol treatment did not significantly improve performance on the stimulus discrimination/reversal learning task. In fact, estradiol was associated with a significant increase in incorrect responses on this task after reversal of the stimulus contingency. In addition, treatments did not significantly affect hippocampal choline acetyltransferase activity or acetylcholine release. This may be an effect of age, or possibly is related to compensatory changes associated with long-term cholinesterase inhibitor treatment. The data suggest that treating with a cholinesterase inhibitor can enhance the effects of estradiol on acquisition of a DMP task by old rats following a long period of hormone deprivation. This could be of particular benefit to older women who have not used hormone therapy for many years and are beginning to show signs of mild cognitive impairment. Potential mechanisms for these effects are discussed.

Estrogen Receptor β Does Not Influence Ischemic Tolerance in the Aged Female Rat Heart

Ischemic heart disease remains the leading cause of morbidityand mortality in aged women, with a 2- to 3-fold increased incidencefollowing menopause. Clinical trials have failed to demonstrate cardioprotectivebenefit from chronic estrogen (E2) replacement therapy, yet protective effects of E2 occur in adult animal models and are in part mediated by non-genomic estrogen receptor α (ERα) signaling. The role of ERβ is less clear. The purpose of the present study was to determine the efficacy of acute ERβ activation on reducing cardiac ischemia/reperfusion (I/R) injury in aged E2-deficient female rats. Hearts were isolated from adult (6mo; n=9), aged (24mo; n=13), and aged ovariectomized (OVX; n=14) F344 rats. Hearts were perfused in Langendorff mode and subjected to 47 min of global I and 60 min of R. Rats were acutely treated with the ERβ-agonist diarylpropionitrile (DPN) 45 min prior to I/R (5μg/kg, s.c.), and mRNA isolated to determine ERβ expression. Here, for the first time, our data suggest that acute treatment with DPN does not affect functional recovery following I/R injury in adult, aged, or aged OVX female rats. Additionally, we were unable to detect ERβ mRNA in the adult or aged female rat myocardium. These data indicate that acute ERβ activation does not impact I/R injury in the female rat heart and bring into question the relevance of non-genomic ERβ signaling during I/R injury. Funding Source: NIH R01 HL091097

Effect of resveratrol on fat mobilization

Higher levels of body fat are associated with increased risk for development of numerous adverse health conditions. Phytochemicals are potential agents to inhibit differentiation of preadipocytes, stimulate lipolysis, and induce apoptosis of existing adipocytes, thereby reducing adipose tissue mass. Resveratrol decreased adipogenesis and viability in maturing preadipocytes; these effects were mediated not only through down-regulating adipocyte specific transcription factors and enzymes but also by genes that modulate mitochondrial function. Additionally, resveratrol increased lipolysis and reduced lipogenesis in mature adipocytes. In addition, combining resveratrol with other natural products produced synergistic activities from actions on multiple molecular targets in the adipocyte life cycle. Treatment of mice with resveratrol alone was shown to improve resistance to weight gain caused by a high-fat diet. Moreover, dietary supplementation of aged ovariectomized rats with a combination of resveratrol and vitamin D, quercetin, and genistein not only decreased weight gain but also inhibited bone loss. Combining several phytochemicals, including resveratrol, or using them as templates for synthesizing new drugs, provides a large potential for using phytochemicals to target adipocyte adipogenesis, apoptosis, and lipolysis.

Osteoprotective effects of Fructus Ligustri Lucidi aqueous extract in aged ovariectomized rats

BackgroundFructus Ligustri Lucidi (FLL) is a commonly used herb for treating bone disorders in Chinese medicine. The present study investigates the anti-osteoporotic activity of FLL aqueous extract in the model of postmenopausal bone loss in aged ovariectomized (OVX) female rats.MethodsAfter eight weeks of treatment of FLL or water, the lumbar spine was scanned by peripheral quantitative computed tomography (pQCT). Effects of FLL water extract on osteogenic and adipogenic differentiations in rat mesenchymal stem cells (MSCs) were assessed by biochemical methods and staining.ResultsFLL aqueous extract significantly inhibited bone mineral density (BMD) loss in total, trabecular and cortical bones without affecting body weight and uterus wet weight. FLL extract significantly promoted osteogenesis and suppressed adipogenesis in MSCs as indicated by the elevated alkaline phosphatase activity, calcium deposition levels and decreased adipocyte number in a dose-dependent manner without cytotoxic effects. Real-time PCR analysis revealed significant increase of osteoprotegerin (OPG)-to-receptor activator for nuclear factor-κB ligand (RANKL) mRNA, indicating a decrease in osteoclastogenesis.ConclusionThe present study demonstrates the osteoprotective effects of FLL aqueous extract on aged OVX rats, stimulation of osteogenesis, inhibition of adipogenesis and osteoclastogenesis in MSCs.

Sclerostin: A gem from the genome leads to bone-building antibodies

Sclerostin: A gem from the genome leads to bone-building antibodies

Captopril improves osteopenia in ovariectomized rats and promotes bone formation in osteoblasts

The present study was designed to investigate the effects of captopril, an angiotensin-converting enzyme inhibitor (ACEI), on bone loss in aged ovariectomized (OVX) rats and its impact on the differentiation of cultured primary osteoblasts. Ten-month-old female Sprague-Dawley rats were used for the study. After 2 months post ovariectomy (OVX), the rats were treated with captopril (1 or 5 mg/kg/day, respectively) for another 2 months. At endpoint, trabecular bone of the fourth lumbar vertebrae (L4) was undecalcified and examined by bone histomorphometry; the fifth lumbar vertebrae (L5) were examined by compression test. Primary osteoblasts were isolated from the calvaria of newborn rats and treated with different concentrations of captopril in a different durations. The content of secreted alkaline phosphatase (ALP) and mRNA expression of collagen I in osteoblasts were determined to demonstrate osteoblast bone formation. In aged rats with estrogen deficiency-induced osteopenia, captopril increased the trabecular area (%BV/TV) of L4 up to 33% and improved biomechanical properties by increasing L5 break stress and elastic modulus when compared to those in the OVX group (P < 0.01). Captopril showed dose-dependent effects on promoting the secretion of ALP and increased mRNA expression of collagen I in the cultured rat osteoblasts. In summary, captopril, one of the most widely used ACEIs, has the potential effects of improving lumbar vertebral bone strength in aged OVX rats and promoting osteoblast bone formation in vitro.

Effects of growth hormone, melatonin, oestrogens and phytoestrogens on the oxidized glutathione (GSSG)/reduced glutathione (GSH) ratio and lipid peroxidation in aged ovariectomized rats

Ovariectomy constitutes a commonly used model in rats and mice for human menopause. After ovariectomy, an imbalance between oxidant production and antioxidant levels appears in favour of the former, with increased oxidative stress and consequently an acceleration of ageing. In the present work, the levels of reduced glutathione (GSH), a relevant antioxidant, and oxidized glutathione (GSSG), an oxidant compound, as well as lipid peroxidation (through malondialdehyde (MDA) levels), were studied in liver, heart, kidney and spleen homogenates of old (24 months of age) unovariectomized and ovariectomized female Wistar rats. The results showed a significant increase of the GSSG/GSH ratio, a marker of oxidative stress, and higher MDA production in all the studied organs of ovariectomized rats as compared with unovariectomized animals. These data confirm the idea that ovariectomy accelerates the ageing process. Administration of growth hormone (GH), melatonin (MEL) and oestrogens (OE), as well as soybean phytoestrogens (PE) for 10 weeks, between 22 and 24 months of age, was able to decrease oxidative stress in the investigated organs of ovariectomized old rats, therefore slowing down the ageing process in those animals.

Acute effects of 17β-estradiol and genistein on insulin sensitivity and spatial memory in aged ovariectomized female rats

Aging is characterized by decline in metabolic function and insulin resistance, and both seem to be in the basis of neurodegenerative diseases and cognitive dysfunction. Estrogens prevent age-related changes, and phytoestrogens influence learning and memory. Our hypothesis was that estradiol and genistein, using rapid-action mechanisms, are able to modify insulin sensitivity, process of learning, and spatial memory. Young and aged ovariectomized rats received acute treatment with estradiol or genistein. Aged animals were more insulin-resistant than young. In each age, estradiol and genistein-treated animals were less insulin-resistant than the others, except in the case of young animals treated with high doses of genistein. In aged rats, no differences between groups were found in spatial memory test, showing a poor performance in the water maze task. However, young females treated with estradiol or high doses of genistein performed well in spatial memory task like the control group. Only rats treated with high doses of genistein showed an optimal spatial memory similar to the control group. Conversely, acute treatment with high doses of phytoestrogens improved spatial memory consolidation only in young rats, supporting the critical period hypothesis for the beneficial effects of estrogens on memory. Therefore, genistein treatment seems to be suitable treatment in aged rats in order to prevent insulin resistance but not memory decline associated with aging. Acute genistein treatment is not effective to restore insulin resistance associated to the early loss of ovarian function, although it can be useful to improve memory deficits in this condition.

Effects of bovine colostrum acid protein on bone loss and hemobiochemistry indexes in rats

At present, researchers all over the world focus on the methods to prevent and cure osteoporosis. Many reports have shown that bovine milk and its basic proteins, and bovine colostrums (BC) and their extracts have positive effects on bone growth of human beings or experimental rats, such as increasing bone mineral density (BMD) and promoting calcium absorption. However, to our best knowledge, the effects of acid proteins from BC (BCAP) on bone properties have not been reported, and the effect on the potential hazard on blood lipids of rats has not been reported. This study investigated the effect of BCAP on bone loss in aged ovariectomized (OVX) rats and the hemobiochemistry parameters (HP) in serum. Forty-eight female Sprague-Dawley rats of clean grade were ovariectomized and another 12 rats received a sham operation. The OVX rats were randomly separated into four groups, i.e. OVX control, OVX low dose (0.04 g·d−1), OVX medium dose (0.20 g·d−1), and OVX high dose (0.40 g·d−1). BCAP were applied in rat diet for 12 weeks and the rats were gavaged once a day. The effects of BCAP on HP, calcium content (CC), and BMD of femur were determined using biochemical analysis, atomic absorption spectrophotometry, and dual-energy X-ray absorptiometry. Results showed that BCAP could increase the femur weight/length. CC of femurs in rats with BCAP were significantly higher than those of shamoperated group and model control group. BCAP increased the BMD of femur. However, BCAP at a low dosage exhibited higher activity than that at a medium or high dosage. BCAP had no particular effects on the HP of rats. It is concluded that BCAP at dose < 0.04 g·d−1 can prevent osteoporosis caused by bone loss due to estrogen reduction in OVX rats, and BCAP (0.04–0.40 g·d−1) has no potential hazard on blood lipids of rats under present experimental condition.

Estradiol Reverses a Calcium-Related Biomarker of Brain Aging in Female Rats

An increase in L-type voltage-gated calcium channel (LTCC) current is a prominent biomarker of brain aging and is believed to contribute to cognitive decline and vulnerability to neuropathologies. Studies examining age-related changes in LTCCs have focused primarily on males, although estrogen (17beta-estradiol, E2) affects calcium-dependent activities associated with cognition. Therefore, to better understand brain aging in females, the effects of chronic E2 replacement on LTCC current activity in hippocampal neurons of young and aged ovariectomized rats were determined. The zipper slice preparation was used to expose cornu ammonis 1 (CA1) pyramidal neurons for recording LTCC currents using the cell-attached patch-clamp technique. We found that an age-related increase in LTCC current in neurons from control animals was prevented by E2 treatment. In addition, in situ hybridization revealed that within stratum pyramidale of the CA1 area, mRNA expression of the Ca(v)1.2 LTCC subunit, but not the Ca(v)1.3 subunit, was decreased in aged E2-treated rats. Thus, the reported benefits of E2 on cognition and neuronal health may be attributed, at least in part, to its age-related decrease in LTCC current.

Sclerostin Antibody Treatment Increases Bone Formation, Bone Mass, and Bone Strength in a Rat Model of Postmenopausal Osteoporosis

The development of bone-rebuilding anabolic agents for potential use in the treatment of bone loss conditions, such as osteoporosis, has been a long-standing goal. Genetic studies in humans and mice have shown that the secreted protein sclerostin is a key negative regulator of bone formation, although the magnitude and extent of sclerostin's role in the control of bone formation in the aging skeleton is still unclear. To study this unexplored area of sclerostin biology and to assess the pharmacologic effects of sclerostin inhibition, we used a cell culture model of bone formation to identify a sclerostin neutralizing monoclonal antibody (Scl-AbII) for testing in an aged ovariectomized rat model of postmenopausal osteoporosis. Six-month-old female rats were ovariectomized and left untreated for 1 yr to allow for significant estrogen deficiency-induced bone loss, at which point Scl-AbII was administered for 5 wk. Scl-AbII treatment in these animals had robust anabolic effects, with marked increases in bone formation on trabecular, periosteal, endocortical, and intracortical surfaces. This not only resulted in complete reversal, at several skeletal sites, of the 1 yr of estrogen deficiency-induced bone loss, but also further increased bone mass and bone strength to levels greater than those found in non-ovariectomized control rats. Taken together, these preclinical results establish sclerostin's role as a pivotal negative regulator of bone formation in the aging skeleton and, furthermore, suggest that antibody-mediated inhibition of sclerostin represents a promising new therapeutic approach for the anabolic treatment of bone-related disorders, such as postmenopausal osteoporosis.

Effects of long-term ovariectomy on anxiety and behavioral despair in rats

Clinical and pre-clinical findings point to the critical role of ovarian hormones in modulating anxiety and depressive symptoms in female. However, few studies investigated the effects of long-term ovarian hormones withdrawal on animal behavior. The current study evaluated the behavioral effects of long-term ovariectomy (performed at 3 months of life) in adult (6 months old) and aged (18 months old) rats subjected to the elevated plus-maze and forced swimming tests. A substantial reduction in the time spent in open arms in adult and aged ovariectomized rats was observed compared to intact animal from the same age. A significant increase in the immobility time was observed in aged rats, ovariectomized or not, compared to adult rats. It should be noted that no alterations in the spontaneous locomotion were detected among groups. In addition, a reduction in serum concentrations of 17β-estradiol was observed in adult ovariectomized and aged sham and ovariectomized rats compared to adult intact animals. Taken together, these findings suggest that anxiety-related behaviors were affected by ovariectomy, but not aging. However, the depressive-like behavior observed in aged rats seems to be much more influenced by senescence than ovarian hormones withdrawal. The presented results are discussed considering the effects of gradual and abrupt reduction of ovarian steroids concentrations, and the influence of aging on behavior of female rats.

Donepezil treatment restores the ability of estradiol to enhance cognitive performance in aged rats: Evidence for the cholinergic basis of the critical period hypothesis

Recent studies suggest that the ability of estradiol to enhance cognitive performance diminishes with age and/or time following loss of ovarian function. We hypothesize that this is due, in part, to a decrease in basal forebrain cholinergic function. This study tested whether donepezil, a cholinesterase inhibitor, could restore estradiol effects on cognitive performance in aged rats that had been ovariectomized as young adults. Rats were ovariectomized at 3 months of age, and then trained on a delayed matching to position (DMP) T-maze task, followed by a configural association (CA) operant condition task, beginning at 12–17 or 22–27 months of age. Three weeks prior to testing, rats started to receive either donepezil or vehicle. After one week, half of each group also began receiving estradiol. Acclimation and testing began seven days later and treatment continued throughout testing. Estradiol alone significantly enhanced DMP acquisition in middle-aged rats, but not in aged rats. Donepezil alone had no effect on DMP acquisition in either age group; however, donepezil treatment restored the ability of estradiol to enhance DMP acquisition in aged rats. This effect was due largely to a reduction in the predisposition to adopt a persistent turn strategy during acquisition. These same treatments did not affect acquisition of the CA task in middle-aged rats, but did have small but significant effects on response time in aged rats. The data are consistent with the idea that estrogen effects on cognitive performance are task specific, and that deficits in basal forebrain cholinergic function are responsible for the loss of estradiol effect on DMP acquisition in aged ovariectomized rats. In addition, the data suggest that enhancing cholinergic function pharmacologically can restore the ability of estradiol to enhance acquisition of the DMP task in very old rats following long periods of hormone deprivation. Whether donepezil has similar restorative effects on other estrogen-sensitive tasks needs to be explored.

Effects of 17&amp;beta;-estradiol treatment over memory of young, adult and aged ovariectomized female Wistar rats

Event Abstract Back to Event Effects of 17β-estradiol treatment over memory of young, adult and aged ovariectomized female Wistar rats Anete Curte-Ferraz1*, Agata Kiss1, Marcela Cordellini1, Giovana Piazzetta1, Ana Marcia-Delattre1 and Karin Cristine-Pinto1 1 Federal University of Parana, Brazil Clinical and experimental evidences suggest that estrogens have a great impact over cognitive function, since they show signs of neurotrophic and neuroprotective effect in certain brain regions, such as the hippocampus. However, a recent large scale study (Women’s Health Initiative Memory Study-WHIMS) surprisingly indicated that certain hormonal treatments could have no effect over cognition and dementia in women. The relatively limited number of studies comparing estrogenic treatment at different ages raises the question whether age alters the response to the hormonal treatment. For that matter, our study aims to analyze the possible effects of 17â-estradiol treatment over spatial reference memory of female Wistar young (2 months), adult (7 months) and aged (11 months) ovariectomized rats in the Morris water maze, as well as latent behavioral implications of such treatment over animals’ emotionality through the open field test. The ovariectomized animals were subdivided according to the therapy into estrogen and corn oil groups. Also, a third non-ovariectomized group served as control. In the young rats, no significantly results were found in any behavioral and cognitive test, indicating that estrogen therapy has no influence over such age. On the other hand, although no difference was found among the adult groups in the open field, rats treated with estrogen demonstrated enhanced memory performance in the Morris water maze when compared to the corn oil and control groups. Aged animals results are still being processed, but our final objective is to consider plausible relations between the aforementioned treatment and different ages, shedding light to many raised questions. This topic represents a promising area for biomedical research, since potential utilization of such molecules is related to new therapeutic strategies to combat aging and neurodegenerative events. Conference: 41st European Brain and Behaviour Society Meeting, Rhodes Island, Greece, 13 Sep - 18 Sep, 2009. Presentation Type: Poster Presentation Topic: Poster presentations Citation: Curte-Ferraz A, Kiss A, Cordellini M, Piazzetta G, Marcia-Delattre A and Cristine-Pinto K (2009). Effects of 17β-estradiol treatment over memory of young, adult and aged ovariectomized female Wistar rats. Conference Abstract: 41st European Brain and Behaviour Society Meeting. doi: 10.3389/conf.neuro.08.2009.09.122 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 08 Jun 2009; Published Online: 08 Jun 2009. * Correspondence: Anete Curte-Ferraz, Federal University of Parana, Curitiba, Brazil, anete@ufpr.br Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Anete Curte-Ferraz Agata Kiss Marcela Cordellini Giovana Piazzetta Ana Marcia-Delattre Karin Cristine-Pinto Google Anete Curte-Ferraz Agata Kiss Marcela Cordellini Giovana Piazzetta Ana Marcia-Delattre Karin Cristine-Pinto Google Scholar Anete Curte-Ferraz Agata Kiss Marcela Cordellini Giovana Piazzetta Ana Marcia-Delattre Karin Cristine-Pinto PubMed Anete Curte-Ferraz Agata Kiss Marcela Cordellini Giovana Piazzetta Ana Marcia-Delattre Karin Cristine-Pinto Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Progesterone decreases cortical and sub-cortical edema in young and aged ovariectomized rats with brain injury

Progesterone decreases cortical and sub-cortical edema in young and aged ovariectomized rats with brain injury

In vitro and in vivo evidence for stimulation of bone resorption by an EP4 receptor agonist and basic fibroblast growth factor: Implications for their efficacy as bone anabolic agents

Prostaglandin E2 receptor subtype 4 agonists (EP4A) and basic fibroblast growth factor (FGF2) stimulate bone formation, but their effects on bone resorption are controversial. To provide additional insight into the skeletal effects of EP4A and FGF2, their regulation of expression of genes associated with bone formation and resorption in aged ovariectomized (OVX) rats and in cultured mouse bone marrow cells was determined. RNA was isolated from lumbar vertebrae of OVX rats (16 months of age) treated daily for 3 weeks with FGF2 or EP4A and processed for quantitative real time-PCR analyses. mRNA expression for the receptor activator of NF-κB ligand (RANKL) and cathepsin K (CTSK), but not osteoprotegerin (OPG), were upregulated by both FGF2 and EP4A. Addition of FGF2 and EP4A to the medium of cultured mouse bone marrow cells increased the formation of tartrate resistant acid phosphatase (TRAP) positive cells, upregulated the expression of RANKL and CTSK, and downregulated expression for OPG. EP4A also increased the formation of actin rings, an indicator of osteoclast activation, in a dose dependent manner in osteoclasts cultured on bone slices and triggered the formation of pits as revealed by a pitting assay. Gene expression for osterix (OSX) and IGF-2, genes associated with bone formation, was significantly greater in FGF2-treated OVX rats compared with EP4A-treated OVX rats. These findings at the molecular level are consistent with previous tissue-level histomorphometric findings, and at the doses tested, support the contention that FGF2 has a stronger bone anabolic effect than EP4A. The results of these in vivo and in vitro analyses clarify the effects of FGF2 and EP4A on bone formation and resorption, and provide insight into differences in the efficacy of two potential bone anabolic agents for restoration of lost bone mass in the osteopenic, estrogen-deplete skeleton.

Sevelamer Restores Bone Volume and Improves Bone Microarchitecture and Strength in Aged Ovariectomized Rats

Sevelamer hydrochloride, a noncalcium phosphate binder, has been shown to reduce coronary artery and aortic calcification, and to improve trabecular bone mineral density in hemodialysis patients with chronic kidney disease. Here, we examined whether sevelamer given orally for 12 wk with normal food could restore bone volume (BV) and strength in aged ovariectomized (OVX) rats starting at 4 wk after OVX. Dual-energy x-ray absorptiometry, microcomputerized tomography, and bone histomorphometry analyses showed that OVX animals receiving sevelamer had increased trabecular BV (51%), trabecular number (43%), trabecular thickness (9%), cortical thickness (16%), mineral apposition rate (103%), bone formation rate (25%), and enhanced cortical and trabecular bone mechanical strength as compared with OVX rats. Sevelamer decreased collagen C telopeptide, increased osteocalcin levels, and decreased phosphate and magnesium levels without affecting calcium levels in the blood. Although sevelamer was not absorbed systemically, it stimulated osteoblast differentiation in BM-derived mesenchymal stem cell cultures, as evaluated by alkaline phosphatase positive colony-forming units, and inhibited recombinant human soluble receptor activator of nuclear factor-kappaB ligand-induced osteoclast differentiation, as evaluated by tartrate-resistant acid phosphatase positive cells in bone mineral-hematopoietic stem cell cultures. Surface enhanced laser desorption/ionization time-of-flight mass spectrometry analysis revealed that 69 proteins were differently expressed after OVX, of which 30% (20 of 69) were reversed to sham activity after sevelamer intake. PTH, fibroblast growth factor-23, and cytokine profile in serum were not significantly changed. Together, these results suggest that sevelamer in food increases the BV and improves biomechanical properties of bone in OVX rats.