Trends in the Use of Minimally Invasive Adnexal Surgery in the United States.

OBJECTIVE: To examine the utilization of minimally invasive adnexal surgery, including ovarian cystectomy and oophorectomy, among women with benign gynecologic diseases and compare the associated morbidity and mortality of minimally invasive and open surgery. METHODS: Women with benign ovarian pathology who underwent an ovarian cystectomy or oophorectomy from 2016 through 2018 in the Nationwide Ambulatory Surgery Sample and Nationwide Inpatient Sample databases were included. Patients with a diagnosis of gynecologic malignancy or concurrent hysterectomy were excluded. Population-level weighted estimates were developed, and perioperative morbidity, mortality, and hospital charges were examined based on surgical approach for each procedure. RESULTS: The cohort included 351,207 women who underwent oophorectomy and 220,893 women who underwent cystectomy, when weighted representing 547,836 and 328,408 patients, respectively, nationwide. A minimally invasive surgical approach was used in 294,190 (89.6%) patients who underwent ovarian cystectomy, and in 478,402 (87.3%) of patients who underwent oophorectomy. Use of minimally invasive surgery for cystectomy increased from 88.7% in 2016 to 91.0% in 2018, and the rate of minimally invasive surgery for oophorectomy increased from 85.8% to 88.7% over the same time period (P<.001 for both). The complication rates for ovarian cystectomy were 2.7% for minimally invasive surgery and 8.8% for laparotomy (P<.001); for oophorectomy the complication rate was 3.1% for minimally invasive surgery and 22.9% for laparotomy (P<.001). CONCLUSION: Minimally invasive surgery is used in the majority of women who are undergoing oophorectomy and ovarian cystectomy for benign indications. Compared with laparotomy, minimally invasive surgery is associated with fewer complications.

Lumbar Disk Degeneration in Female Patients with and without Ovariectomy: A Case-Control Study.

OBJECTIVE: We sought to provide clinical evidence of the potential influence of ovariectomy (OVX) on intervertebral disk degeneration. METHODS: We retrospectively reviewed patients with a history of OVX who visited our hospital for lower back pain. In addition, 60 age-matched patients without OVX were randomly selected as control subjects. Next, the following demographic data were recorded and compared among groups: age, body mass index, duration of OVX, history of smoking, alcohol use, hypertension, diabetes, cardiocerebrovascular disease, hyperlipemia, osteoporosis, and degenerative spondylolisthesis. Next, the severity of lumbar disk degeneration, evaluated by the modified Pfirrmann grading system, was compared between groups. Data analyses were performed with SPSS 20.0. software. RESULTS: A total of 15 OVX (unilateral, n = 10; bilateral, n = 5) patients were included with a mean age of 62.40 ± 10.64. The average durations of OVX were 21.33 ± 9.24 years. There existed no remarkable intergroup differences in the demographic data (P > 0.05). Overall, the average Pfirrmann grading scores from L1/2 to L5/S1 presented as L1/2 < L2/3 < L3/4 ≤ L5/S1 ≤ L4/5, with no marked differences between groups (P > 0.05). Nevertheless, OVX groups displayed a relatively higher score at each level than non-OVX group. Moreover, the scores from L3/4 to L5/S1 were higher in the bilateral OVX group relative to the unilateral OVX group while they were equal at L1/2 and L2/3. CONCLUSIONS: Our findings demonstrated that OVX contributed to the progression of lumbar disk degeneration to some extent, but it appeared to be a long-term event.

Inhibition of mitochondrial pyruvate carrier 1 by lapatinib ditosylate mitigates Alzheimer's-like disease in D-galactose/ovariectomized rats.

Mitochondrial, autophagic impairment, excitotoxicity, and also neuroinflammation are implicated in Alzheimer's disease (AD) pathophysiology. We postulated that inhibiting the mitochondrial pyruvate carrier-1 (MPC-1), which inhibits the activation of the mammalian target of rapamycin (mTOR), may ameliorate the neurodegeneration of hippocampal neurons in the rat AD model. To assess this, we used lapatinib ditosylate (LAP), an anti-cancer drug that inhibits MPC-1 through suppression of estrogen-related receptor-alpha (ERR-α), in D-galactose/ovariectomized rats. AD characteristics were developed in ovariectomized (OVX) rats following an 8-week injection of D-galactose (D-gal) (150 mg/kg, i.p.). The human epidermal growth factor receptor-2 (HER-2) inhibitor, LAP (100 mg/kg, p.o.) was daily administered for 3 weeks. LAP protected against D-gal/OVX-induced changes in cortical and hippocampal neurons along with improvement in learning and memory, as affirmed using Morris water maze (MWM) and novel object recognition (NOR) tests. Furthermore, LAP suppressed the hippocampal expression of Aß1-42, p-tau, HER-2, p-mTOR, GluR-II, TNF-α, P38-MAPK, NOX-1, ERR-α, and MPC-1. Also, LAP treatment leads to activation of the pro-survival PI3K/Akt pathway. As an epilogue, targeting MPC-1 in the D-gal-induced AD in OVX rats resulted in the enhancement of autophagy, and suppression of neuroinflammation and excitotoxicity. Our work proves that alterations in metabolic signaling as a result of inhibiting MPC-1 were anti-inflammatory and neuroprotective in the AD model, revealing that HER-2, MPC-1, and ERR-α may be promising therapeutic targets for AD.

The anti-dipsogenic and anti-natriorexigenic effects of estradiol, but not the anti-pressor effect, are lost in aged female rats.

Estradiol (E2) inhibits fluid intake in several species, which may help to defend fluid homeostasis by preventing excessive extracellular fluid volume. Although this phenomenon is well established using the rat model, it has only been studied directly in young adults. Because aging influences the neuronal sensitivity to E2 and the fluid intake effects of E2 are mediated in the brain, we tested the hypothesis that aging influences the fluid intake effects of E2 in female rats. To do so, we examined water and NaCl intake in addition to the pressor effect after central angiotensin II treatment in young (3-4 months), middle-aged (10-12 months), and old (16-18 months) ovariectomized rats treated with estradiol benzoate (EB). As expected, EB treatment reduced water and NaCl intake in young rats. EB treatment, however, did not reduce water intake in old rats, nor did it reduce NaCl intake in middle-aged or old rats. The ability of EB to reduce blood pressure was, in contrast, observed in all three age groups. Next, we also measured the gene expression of estrogen receptors (ERs) and the angiotensin type 1 receptor (AT1R) in the areas of the brain that control fluid balance. ERß, G protein estrogen receptor (GPER), and AT1R were reduced in the paraventricular nucleus of the hypothalamus in middle-aged and old rats, compared to young rats. These results suggest the estrogenic control of fluid intake is modified by age. Older animals lost the fluid intake effects of E2, which correlated with decreased ER and AT1R expression in the hypothalamus.

Prolactin promotes a partial recovery from the atrophy of both male and female gerbil prostates caused by castration.

BACKGROUND: The male and female prostates are controlled by steroid hormones, suffering important morphological and physiological changes after castration. Prolactin is involved in the regulation of the male prostate, having already been identified in the tissue, acting through its receptor PRLR. In the Mongolian gerbil, in addition to the male prostate, the female prostate is also well developed and active in its secretion processes. The aim of the present study was to evaluate the effects of exposure to exogenous prolactin in the prostate of both intact and castrated male and female gerbils in order to establish if prolactin administration can sustain prostate cell activity in conditions of sexual hormone deprivation. METHODS: The morphological analyses were performed by biometric analysis, lesion histological analysis and morphometric-stereological aspects. In addition, immune-cytochemical tests were performed for prolactin and its receptor, as well as for the receptors of androgen and oestrogen and serum prolactin dosage. All data were submitted to ANOVA or Kruskal-Wallis tests for comparison between groups. P < 0.05 was considered to be statistically significant. RESULTS: The results showed a strong influence of prolactin on the morphology of the prostate, with the development of important epithelial alterations, after only 3 days of administration, and an expressive epithelial cell discard process after 30 days of administration. Prolactin acts in synergy with testosterone in males and mainly with oestrogens in females, establishing different steroid hormonal receptor immunoreactivity according to sex. It was also demonstrated that prolactin can assist in the recovery from some atrophic effects caused in the gland after castration, without causing additional tissue damage. CONCLUSIONS: The prolactin and its receptor are involved in the maintenance of the homeostasis of male and female gerbils, and also cause distinct histological alterations after exogenous exposure for 3 and 30 days. The effects of prolactin are related to its joint action on androgens and oestrogens and it can also assist in the recovery from the atrophic effects of castration.

Changing trends in Black-White racial differences in surgical menopause: a population-based study.

BACKGROUND: Bilateral oophorectomy before menopause, or surgical menopause, is associated with negative health outcomes, including an increased risk for stroke and other cardiovascular outcomes; however, surgical menopause also dramatically reduces ovarian cancer incidence and mortality rates. Because there are competing positive and negative sequelae associated with surgical menopause, clinical guidelines have not been definitive. Previous research indicates that White women have higher rates of surgical menopause than other racial groups. However, previous studies may have underestimated the rates of surgical menopause among Black women. Furthermore, clinical practice has changed dramatically in the past 15 years, and there are no population-based studies in which more recent data were used. Tracking actual racial differences among women with surgical menopause is important for ensuring equity in gynecologic care. OBJECTIVE: This population-based surveillance study evaluated racial differences in the rates of surgical menopause in all inpatient and outpatient settings in a large, racially diverse US state with historically high rates of hysterectomy. STUDY DESIGN: We evaluated all inpatient and outpatient surgeries in North Carolina from 2011 to 2014 for patients aged between 20 and 44 years. Surgical menopause was defined as a bilateral oophorectomy, with or without an accompanying hysterectomy, among North Carolina residents. International Classification of Diseases, Ninth Revision, and Current Procedural Terminology codes were used to identify inpatient and outpatient procedures, respectively, and diagnostic indications. We estimated age-, race-, and ethnicity-specific rates of surgical menopause using county-specific population estimates based on the 2010 United States census. We used Poisson regression with deviance-adjusted residuals to estimate the incidence rate ratios in the entire state population. We tested changes in surgery rates over time (reference year, 2011), differences by setting (reference, inpatient), and differences by race and ethnicity (reference, non-Hispanic White). We then described the surgery rates between non-Hispanic White and non-Hispanic Black patients. RESULTS: Between 2011 and 2014, 11,502 surgical menopause procedures for benign indications were performed in North Carolina among reproductive-aged residents. Most (95%) of these surgeries occurred concomitant with a hysterectomy. Over the 4-year study period, there was a 39% reduction in inpatient surgeries (incidence rate ratio, 0.61) and a 100% increase in outpatient surgeries (incidence rate ratio, 2.0). Restricting the analysis to surgeries among non-Hispanic White and Black patients, the increase in outpatient surgeries was significantly higher among non-Hispanic Black women (P<.01) for year-race interaction (reference, 2011 and non-Hispanic White). The overall rates of bilateral oophorectomy for non-Hispanic Black women rose more quickly than for non-Hispanic White women (P<.01). In 2011, the rate of surgical menopause was greater among White women than among Black women (17.7 vs 13.2 per 10,000 women). By 2014, the racial trends were reversed (rate, 24.8 per 10,000 for non-Hispanic White women and 28.4 per 10,000 for non-Hispanic Black women). CONCLUSION: Our findings suggest that the rates of surgical menopause increased in North Carolina in the early 2010s, especially among non-Hispanic Black women. By 2014, the rates of surgical menopause among non-Hispanic Black women had surpassed that of non-Hispanic White women. Given the long-term health consequences associated with surgical menopause, we propose potential drivers for the racially-patterned increases in the application of bilateral oophorectomy before the age of 45 years.

Preliminary study of ovariectomy and chronic losartan-induced alterations in brain AT1 receptors.

Women who undergo oophorectomy prior to the age of natural menopause have a higher risk of neurological and psychological impairment. Treatment with the angiotensin receptor blocker (ARB) losartan for 10 weeks following ovariectomy of Long-Evans rats at 3 months of age reduced the ovariectomy-induced cognitive decrements. Following completion of the behavioral experiments, (Campos et al., 2019), the brains were harvested for preliminary receptor autoradiographic studies of AT1 receptor (AT1R) binding in selected brain regions using quantitative densitometric analysis of autoradiograms of 125I-sarcosine1, isoleucine8 angiotensin II binding. Four of the brain regions (amygdala, ventral subiculum, piriform cortex, and cingulate cortex) are associated with cognitive and emotional behavior while one (lateral hypothalamus) is associated with homeostasis. The density of AT1R varied by region: ventral subiculum > amygdala and cingulate cortex, and piriform cortex > cingulate cortex. Losartan treatment decreased AT1R binding in the ventral subiculum of sham and ovariectomized rats by 41.6%, and 46% in the piriform cortex of the sham rats, but tended to increase AT1R binding in the piriform cortex and cingulate cortex 77% and 107%, respectively, in the ovariectomized rats. AT1R binding did not differ significantly between intact male and sham-vehicle female rats among surveyed brain regions. These results suggest that losartan-induced changes in brain AT1R expression may contribute to the reduced anxiety-like behavior and memory impairments seen in ovariectomized rats, but replication of these observations will be needed to determine the extent to which brain AT1R changes mediate the adverse behavioral effects of ovariectomy.

Polyphenol-rich leaf of Aphanamixis polystachya averts liver inflammation, fibrogenesis and oxidative stress in ovariectomized Long-Evans rats.

Aphanamixis polystachya (Wall.) R.Parker, locally known as Pithraj, is a medicinal herb having enormous traditional applications. However, the scientific rationale underlying the ethnomedicinal claims was not well-founded. The current investigation aimed to explore the mechanistic insights of protective effects of ethanol extract of A. polystachya leaf (PT), given orally, on the chemical-intoxicated hepatic inflammation and fibrosis in Long-Evans female overiectomized rats. The GC-MS and HPLC-DAD analysis of PT revealed the presence of several bioactive metabolites, including polyphenolic compounds. Catechin hydrate, caffeic acid, syringic acid, epicatechin and p-coumaric acid have been identified and quantified in the ethanol extract of PT leaf. Intoxication with CCl4 developed the oxidative stress, fibrosis and inflammation in liver of rats. Moreover, thiobarbituric acid reactive substances (TBARS), nitric oxide (NO), advanced protein oxidation product (APOP) level were found increased; whereas superoxide dismutase (SOD) and catalase activities in the plasma and liver were decreased in CCl4 administered rats. Treatment with PT prominently mitigated the oxidative stress (TBARS, NO, APOP), and inflammatory (MPO) markers and improved the endogenous antioxidant enzymes (catalase and SOD) activities in CCl4-intoxicated rats. Additionally, histological assessment confirmed the clear manifestation of inflammation and fibrosis in the liver of CCl4-intoxicated rats, which was prevented by PT and silymarin treatment. In conclusion, PT treatment may protect the liver in CCl4-administered rats, probably by mitigating oxidative stress, inflammation and fibrosis, and also augmenting the function of the antioxidant enzymes.

Cajanolactone A, a stilbenoid from Cajanus cajan, inhibits energy intake and lipid synthesis/storage, and promotes energy expenditure in ovariectomized mice.

BACKGROUND: We had reported that cajanolactone A (CLA) from Cajanus cajan dose-dependently inhibited ovariectomy-induced obesity and liver steatosis in mice, showing potential to prevent postmenopausal obesity and fatty liver. In this study, the role of CLA in the regulation of energy and lipid homeostasis was investigated. METHODS: Ovariectomized mice treated with CLA or vehicle for 12 weeks were performed a 48 h monitoring for energy metabolism and food uptake. After that, hypothalami, perigonadal (pWATs), inguinal (iWATs) and brown (BATs) adipose tissues, livers, sera, and fecal and cecal contents were collected and analyzed. FINDINGS: In CLA-treated mice, we observed reduced food uptake; increased energy expenditure; inhibited expression of orexigenic genes (ORX, ORXR2, pMCH and Gal) in the hypothalami, of lipogenic genes (CD36, SREBP-1c, ChREBP, PPARγ) in the livers, and of lipid storage proteins in the WATs (FSP27, MEST and caveolin-1) and livers (FSP27, Plin2 and Plin5); stimulated expression of metabolism-related proteins (pATGL and Echs1) in the adipose tissues and of thermogenic protein (UCP1) in the inguinal WATs; increased BAT content; increased mitochondria in the pWATs and livers; inhibited angiogenesis in the pWATs; and altered gut microbiome diversity with an increased abundance of Bacteroides. INTERPRETATION: CLA prevents ovariectomy-induced obesity and liver steatosis via regulating energy intake and lipid synthesis/storage, promoting UCP1-dependent heat production, and protecting the mitochondrial function of hepatocytes and adipocytes. The improved gut microecology and inhibited angiogenesis may also contribute to the anti-obese activity of CLA.

Effects of ovariectomy on the inputs from the medial nucleus of the amygdala to the ventromedial nucleus of the hypothalamus in young adult rats.

During puberty, sexual hormones induce crucial changes in neural circuit organization, leading to significant sexual dimorphism in adult behaviours. The ventrolateral division of the ventromedial nucleus of the hypothalamus (VMHvl) is the major neural site controlling the receptive component of female sexual behaviour, which is dependent on ovarian hormones. The inputs to the VMHvl, originating from the medial nucleus of the amygdala (MeA), transmit essential information to trigger such behaviour. In this study, we investigated the projection pattern of the MeA to the VMHvl in ovariectomized rats at early puberty. Six-week-old Sprague-Dawley rats were ovariectomized (OVX) and, upon reaching 90 days of age, were subjected to iontophoretic injections of the neuronal anterograde tracer Phaseolus vulgaris leucoagglutinin into the MeA. Projections from the MeA to the VMHvl and to other structures included in the neural circuit responsible for female sexual behaviour were analysed in the Control and OVX groups. The results of the semi-quantitative analysis showed that peripubertal ovariectomy reduced the density of intra-amygdalar fibres. The stereological estimates, however, failed to find changes in the organization of the terminal fields of nerve fibres from the MeA to the VMHvl in the adult. The present data show that ovariectomized rats during the peripubertal phase did not undergo significant changes in MeA fibres reaching the VMHvl; however, they suggest a possible effect of ovariectomy on MeA connectivity under amygdalar subnuclei.

Fever Induced by Zymosan A and Polyinosinic-Polycytidylic Acid in Female Rats: Influence of Sex Hormones and the Participation of Endothelin-1.

Sex differences in the immune response can also affect the febrile response, particularly the fever induced by lipopolysaccharide (LPS). However, other pathogen-associated molecular patterns, such as zymosan A (Zym) and polyinosinic-polycytidylic acid (Poly I:C), also induce fever in male rats with a different time course of cytokine release and different mediators such as endothelin-1 (ET-1). This study investigated whether female sex hormones affect Zym- and Poly I:C-induced fever and the involvement of ET-1 in this response. The fever that was induced by Zym and Poly I:C was higher in ovariectomized (OVX) female rats compared with sham-operated female rats. Estrogen replacement in OVX females reduced Zym- and Poly I:C-induced fever. The ETB receptor antagonist BQ788 reversed the LPS-induced fever in cycling females but not in OVX females. BQ788 did not alter the fever that was induced by Zym or Poly I:C in either cycling or OVX females. These findings suggest that the febrile response in cycling females is lower, independently of the stimulus that is inducing it and is probably controlled by estrogen. Also, ET-1 seems to participate in the febrile response that was induced by LPS in males and cycling females but not in the LPS-induced fever in OVX females. Additionally, ET-1 was not involved in the febrile response that was induced by Zym or Poly I:C in females.

The Role of Estrogen in Anxiety-Like Behavior and Memory of Middle-Aged Female Rats.

Aging in women is associated with low estrogen, but also with cognitive decline and affective disorders. Whether low estrogen is causally responsible for these behavioral symptoms is not clear. Thus, we aimed to examine the role of estradiol in anxiety-like behavior and memory in rats at middle age. Twelve-month old female rats underwent ovariectomy (OVX) or were treated with 1 mg/kg of letrozole-an aromatase inhibitor. In half of the OVX females, 10 µg/kg of 17ß-estradiol was supplemented daily for 4 weeks. Vehicle-treated sham-operated and OVX females served as controls. For behavioral assessment open field, elevated plus maze and novel object recognition tests were performed. Interaction between ovarian condition and additional treatment had the main effect on anxiety-like behavior of rats in the open field test. In comparison to control females, OVX females entered less frequently into the center zone of the open field (p < 0.01) and showed lower novel object discrimination (p = 0.05). However, estradiol-supplemented OVX rats had higher number of center-zone entries (p < 0.01), spent more time in the center zone (p < 0.05), and showed lower thigmotaxis (p < 0.01) when compared to OVX group. None of the hormonal manipulations affected anxiety-like behavior in the elevated plus maze test significantly, but a mild effect of interaction between ovarian condition and treatment was shown (p = 0.05). In conclusion, ovariectomy had slight negative effect on open-field ambulation and short-term recognition memory in middle-aged rats. In addition, a test-specific anxiolytic effect of estradiol supplementation was found. In contrast, letrozole treatment neither affected anxiety-like behavior nor memory.

Decreased bone mineral density in ovariectomized mice is ameliorated after subsequent repeated intermittent administration of (R)-ketamine, but not (S)-ketamine.

AIM: Depression is a common symptom in people with osteoporosis. (R)-ketamine produced greater potency and longer-lasting antidepressant-like actions than (S)-ketamine in rodents. Here, we examined the effects of two ketamine enantiomers on the reduced bone mineral density (BMD) in the ovariectomized (OVX) mice which is an animal model of postmenopausal osteoporosis. METHODS: Female ddY mice were OVX or sham-operated. Subsequently, saline (10 mL/kg/d, twice weekly), (R)-ketamine (10 mg/kg/d, twice weekly), or (S)-ketamine (10 mg/kg/d, twice weekly) was administered intraperitoneally into OVX or sham mice for the 6 weeks. The femur from all mice was collected 3 days after the final injection, and BMD in the femur was measured. RESULTS: The reduction of cortical BMD and total BMD in the OVX mice was significantly ameliorated after subsequent repeated intermittent administration of (R)-ketamine, but not (S)-ketamine. CONCLUSION: The study shows that (R)-ketamine can ameliorate the reduced cortical BMD and total BMD in OVX mice. Therefore, (R)-ketamine would be a novel therapeutic drug for women with osteoporosis.

Tempe, Tofu, and Amyloid-ß 1-40 Serum Levels in Ovariectomized Rats.

BACKGROUND: Estrogens have been found to reduce amyloid-ß (Aß) levels, a risk factor associated with dementia. We hypothesized that phytoestrogenic soybean products such as tempe and tofu might show similar effects. OBJECTIVE: The aim of this study were to analyze the effect of tempe and tofu flour on Aß1-40 serum levels in ovariectomized rats. METHODS: This research was conducted on female Sprague Dawley rats, aged 12 months. Before the intervention rats underwent ovariectomy (OVx) and were grouped into 5 intervention groups which were given tempe flour, tofu flour, estradiol, or casein as an active control. There was also a non-OVx control group which was fed a normal diet. RESULTS: The intake of tempe and tofu flour decreased Aß serum levels in all estrogen and phytoestrogenic treatment groups, offsetting effects of OVx (but not in the casein group, where Aß levels rise). CONCLUSION: The tempe flour group showed the strongest decrease in serum Aß levels compared to the other groups. Future studies should investigate whether tempe can reduce Aß levels in patients with dementia.

Optimized integration of fluoxetine and 7, 8-dihydroxyflavone as an efficient therapy for reversing depressive-like behavior in mice during the perimenopausal period.

Fluoxetine (FLX) has been considered as an effective anti-depressant drug. Besides, previous studies reported reasonable anti-depressant effects for 7, 8-dihydroxyflavone (7, 8 DHF). However, the combination of FLX and 7, 8 DHF in a well-established depression model has not been explored. In this study, we demonstrate that the 7, 8 DHF can improve the anti-depressant efficacy of FLX in a chronic unpredictable mild stress (CUMS)-induced depression during the perimenopausal period. The corresponding mechanism of FLX+7, 8 DHF therapy and the effect of ANA-12 are also investigated. Moreover, the influences of 7, 8 DHF (5 mg/kg/day), FLX (18 mg/kg/day), and ANA-12 (0.5 mg/kg/day) on a depressive-like behavior are displayed. Inflammatory, autophagic and apoptotic changes of hippocampus and cortex are examined by using western blot, immunofluorescence, and Real-Time Quantitative reverse transcription-polymerase chain reaction (RT-qPCR) techniques. The protein levels of phosphatidylinositol 3 kinase (PI3K)/ protein kinase B (Akt)/mechanistic target of rapamycin (mTOR)/phosphorylated extracellular signal-regulated kinase1/2 (p-ErK 1/2)/brain-derived neurotrophic factor (BDNF)/tropomyosin-related kinase B (TrkB) of hippocampus and cortex are assessed by western blot. The combined FLX and 7, 8 DHF treatment can significantly improve depressive-like behavior in sucrose preference and forced swimming tests accompanied by a noticeable upregulation of autophagy, neuronal nuclei (NeuN), ionized calcium-binding adaptor molecule 1 (Iba1) expressions, and PI3K/Akt/ mTOR/ p-ErK 1/2 signaling pathways. Besides, an obvious increase of the brain-derived neurotrophic factor (BDNF) and TrkB levels are observed with down-regulated inflammation and apoptosis. These findings suggest that the integrated FLX and 7, 8 DHF holds a potential as an efficient treatment to ameliorate depressive-like behavior in perimenopausal patients.

Overexpression of corticotropin-releasing factor in the nucleus accumbens enhances the reinforcing effects of nicotine in intact female versus male and ovariectomized female rats.

This study assessed the role of stress systems in the nucleus accumbens (NAc) in promoting sex differences in the reinforcing effects of nicotine. Intravenous self-administration (IVSA) of various doses of nicotine was compared following overexpression of corticotropin-releasing factor (CRF) in the NAc of female and male rats. Ovariectomized (OVX) females were also included to assess the role of ovarian hormones in promoting nicotine reinforcement. Rats received intra-NAc administration of an adeno-associated vector that overexpressed CRF (AAV2/5-CRF) or green fluorescent protein (AAV2/5-GFP). All rats were then given extended access (23 h/day) to an inactive and an active lever that delivered nicotine. Separate groups of rats received intra-NAc AAV2/5-CRF and saline IVSA. Rats were also allowed to nose-poke for food and water during IVSA testing. At the end of the study, the NAc was dissected and rt-qPCR methods were used to estimate CRF overexpression and changes in CRF receptors (CRFr1, CRFr2) and the CRF receptor internalizing protein, ß-arrestin2 (Arrb2). Overexpression of CRF in the NAc increased nicotine IVSA to a larger extent in intact female versus male and OVX females. Food intake was increased to a larger extent in intact and OVX females as compared to males. The increase in CRF gene expression was similar across all groups; however, in females, overexpression of CRF resulted in a larger increase in CRFr1 and CRFr2 relative to males. In males, overexpression of CRF produced a larger increase in Arrb2 than females, suggesting greater CRF receptor internalization. Our results suggest that stress systems in the NAc promote the reinforcing effectiveness of nicotine in female rats in an ovarian hormone-dependent manner.

Changes in Inflammatory Response, Redox Status and Na+, K+-ATPase Activity in Primary Astrocyte Cultures from Female Wistar Rats Subject to Ovariectomy.

Astrocytes are dynamic glial cells that maintain brain homeostasis, particularly metabolic functions, inflammatory response, and antioxidant defense. Since menopause may be associated with brain dysfunction, in the present study, we evaluated anti- and proinflammatory cytokine release in cortical and hippocampal astrocyte cultures obtained from adult female Wistar rats subjected to ovariectomy, a known experimental model of menopause. We also tested some parameters of metabolic functionality (Na+, K+-ATPase activity) and cellular redox status, such as antioxidant enzyme defenses (superoxide dismutase and catalase) and the intracellular production of reactive oxygen species in this experimental model. Female adult Wistar rats (180 days-age) were assigned to one of the following groups: sham (submitted to surgery without removal of the ovaries) and ovariectomy (submitted to surgery to removal of the ovaries). Thirty days after ovariectomy or sham surgery, we prepared astrocyte cultures from control and ovariectomy surgery animals. Ovariectomized rats presented an increase in pro-inflammatory cytokines (tumor necrosis factor α, interleukins 1ß, 6, and 18) and a decrease in interleukin 10 release, an anti-inflammatory cytokine, in cortical and hippocampal astrocytes, when compared to those obtained from sham group (control). In addition, Na+,K+-ATPase activity decreased in hippocampal astrocytes, but not in cortical astrocyte cultures. In contrast, antioxidant enzymes did not alter in cortical astrocyte cultures, but increased in hippocampal astrocytes. In summary, our findings suggest that ovariectomy is able to induce an inflammatory response in vivo, which could be detected in in vitro astrocytes after approximately 4 weeks.

Bone mesenchymal stem cell therapy for ovariectomized osteoporotic rats: a systematic review and meta-analysis.

BACKGROUND: Previous studies have found that bone mesenchymal stem cells (BMSCs) were capable of self-replication, multi-differentiation, and regeneration. The aim of this study was to carry out a systematic review and meta-analysis of the efficacy of BMSC therapy for ovariectomized rats. METHODS: The PubMed, Embase, Web of Science, China National Knowledge Infrastructure, VIP, and Chinese Sinomed databases were searched systematically from their initiation date to October 5, 2018. Two researchers independently screened the literatures, which used the bone mineral density (BMD), total bone volume by total tissue volume (BV/TV) (%), and trabecular thickness/spacing (Tb/Sp) as the outcome measures. RESULTS: Five eligible studies were selected. In the BMSC treatment groups, the BMD values and normalized BV/TV values remarkably increased. In addition, in the BMSCs plus other treatment groups, the BMD and Tb/Sp values significantly increased. CONCLUSION: This study showed that BMSCs could accelerate callus maturity, ossification and restore mechanical properties of bones in osteoporotic fractures.

Bone microarchitectural parameters can detect oxytocin induced changes prior to bone density on mitigating bone deterioration in rabbit osteoporosis model using micro-CT.

BACKGROUND: This study is aimed to determine the efficacy of X-Ray Microtomography (micro-CT) in predicting oxytocin (OT) treatment response in rabbit osteoporosis(OP) model. METHODS: Sixty-five rabbits were randomly divided into three groups: control group, ovariectomy (OVX) -vehicle and OVX-oxytocin group. The controls underwent sham surgery. OVX-vehicle and OVX-oxytocin groups were subjected to bilateral OVX. The rabbits in OVX-oxytocin group were injected with oxytocin. In the 0th, 4th, 8th, 10th and 12th weeks post OVX operation, bone mineral density (BMD) and bone micro-architectural parameters were measured in three groups. RESULTS: Bone mineral density (BMD), bone volume fraction (BV/TV), Trabecular Number (Tb.N), and Trabecular Thickness (Tb.Th) decreased, while Trabecular Spacing (Tb.Sp) and Structure Model Index (SMI) increased overtime in all the three groups. In OVX-oxytocin group, the bone deterioration tendency is slowing down compared with that of the OVX-vehicle group. The BMD of the OVX-oxytocin group was significantly lower than those in the OVX-vehicle group at 12th week (P = 0.017). BV/TV and Tb.Sp in OVX-oxytocin group changed significantly from 8th week (P = 0.043) and 12th week (P = 0.014), which is earlier than that of BMD and other bone micro-architectural parameters. CONCLUSION: BV/TV and Tb.Sp changed prior to BMD and other bone micro-architectural parameters with oxytocin intervention, which indicate that they are more sensitive markers for predicting early osteoporosis and treatment monitoring when using micro-CT to evaluate osteoporosis rabbit model.

Acute body sodium depletion induces skin sodium mobilization in female Wistar rats.

NEW FINDINGS: What is the central question of this study? Can Na+ depletion mobilize Na+ from the skin reservoir in ovariectomized rats? Does oestrogen replacement change the amount and the dynamics of skin Na+ storage? Is the reduced salt appetite after Na+ depletion in ovariectomized rats with oestrogen replacement related to changes in the skin Na+ ? What is the main finding and its importance? This work demonstrated that acute body Na+ depletion induced by frusemide mobilized the osmotically inactive skin Na+ reservoir to become osmotically active. Oestrogen treatment decreased the induced Na+ intake in ovariectomized rats but did not modulate the inactive Na+ reservoir in control conditions or its mobilization induced by Na+ depletion. ABSTRACT: Oestradiol, which is an important hormone for water and electrolyte balance, also has a role in the inhibition of induced Na+ appetite. Sodium can be stored in the skin in osmotically active or inactive forms, and this skin Na+ reservoir may be involved in the control of body Na+ levels during physiopathological challenges. In this study, we investigated whether the effect of sodium depletion by frusemide can mobilize Na+ from the skin reservoir and whether oestradiol replacement changes or mobilizes the Na+ reserves in the skin. Ovariectomized Wistar rats were treated with vehicle or oestradiol for 7 days to evaluate the effects of oestrogen on the hydroelectrolyte balance, intake responses and skin Na+ and water content in basal conditions. Furthermore, the effects of oestrogen were evaluated after 24 h frusemide-induced whole-body Na+ depletion. Oestradiol-replaced rats exhibited reduced water intake without any significant changes in salt intake, Na+ excretion or water and Na+ skin content in basal conditions. After sodium depletion, both vehicle- and oestradiol-treated rats exhibited an increase in the osmotically active skin Na+ , which was associated with a decrease of the inactive skin Na+ reservoir. Oestrogen decreased the hypertonic saline intake induced by Na+ depletion, but it was not associated with any significant changes in the skin Na+ reservoir. Thus, sodium depletion is able to change the inactive-active skin Na+ reservoir balance. However, the oestrogenic modulation of sodium appetite after Na+ depletion is probably not related to the action of this hormone in the skin Na+ reservoir balance.