- Raloxifene Retards Cartilage Degradation and Improves Subchondral Bone Micro-architecture in Ovariectomized Rats with Patella Baja-Induced- Patellofemoral Joint Osteoarthritis. [Journal Article]
- OCOsteoarthritis Cartilage 2019 Jul 18
- CONCLUSIONS: These findings demonstrate that RAL treatment retards PFJOA progression in an ovariectomized rat model, suggesting that it may be a potential candidate for amelioration of the progression of PFJOA accompanied by postmenopausal OP.
- Sex differences and gonadal hormone regulation of brain cardiolipin, a key mitochondrial phospholipid. [Review]
- JNJ Neuroendocrinol 2019 Jul 19; :e12774
- Cardiolipin (CL) is a phospholipid almost exclusively located in the inner mitochondrial membrane of eukaryotic cells. Due to its unique structure and distribution, CL establishes non-covalent bonds …
Cardiolipin (CL) is a phospholipid almost exclusively located in the inner mitochondrial membrane of eukaryotic cells. Due to its unique structure and distribution, CL establishes non-covalent bonds with a long list of proteins involved in ATP production, mitochondria biogenesis, mitophagy and apoptosis. Thus, CL amount, fatty acid composition and location strongly impact every mitochondrial-dependent function and therefore, the metabolic homeostasis of different tissues. The brain is particularly sensitive to mitochondrial dysfunction due to its high metabolic demand. Several mitochondrial related-neurodegenerative disorders as well as physiological aging show altered CL metabolism. Furthermore, mice lacking enzymes involved in CL synthesis show cognitive impairments. CL content and metabolism, is regulated by gonadal hormones in the developing and adult brain. In neuronal cultures estradiol increases CL content, while adult ovariectomy decreases CL content and alters CL metabolism in hippocampal mitochondria. Transient sex differences in brain CL metabolism have been detected during development. At birth, brain CL had higher proportion of unsaturated fatty acids in the brain of male mice than in the brain of females. In addition, the expression of enzymes involved in CL de novo and recycling synthetic pathways was higher in males. Most of these sex differences were abolished by the neonatal androgenisation of females, suggesting a role for testosterone in the generation of sex differences in brain CL. Regulation of brain CL by gonadal hormones may be involved in their homeostatic and protective actions on neural cells and in the manifestation of sex differences in neurodegenerative disorders. This article is protected by copyright. All rights reserved.
- Effects of lipoic acid and ω-3 long-chain polyunsaturated fatty acids on the kidney in the ovariectomized rat model of menopause. [Journal Article]
- NNutrition 2019 May 29; 66:173-179
- CONCLUSIONS: The results suggest that ovariectomy did not affect the redox profile in the kidneys. LA, DHA, and EPA supplementation increased certain endogenous antioxidants; however, EPA may have a prooxidant effect on the kidneys.
- Prepubertal ovarian inhibition of Light/Dark Box exploration and novelty object investigation in juvenile Siberian hamsters. [Journal Article]
- HBHorm Behav 2019 Jul 13
- The overwhelming majority of research on the role of gonadal hormones in behavioral development has focused on perinatal, pubertal, or adult life stages. The juvenile period has been overlooked becau…
The overwhelming majority of research on the role of gonadal hormones in behavioral development has focused on perinatal, pubertal, or adult life stages. The juvenile period has been overlooked because it is thought to be a time of gonadal quiescence. In the present study, we tested whether prepubertal gonadectomy impacts the behavior of male and female juvenile hamsters on the Light/Dark Box, Novel Object, and Social Approach tests (Experiment 1) and compared these findings to those obtained after adult gonadectomy (Experiment 2). Prepubertal ovariectomy increased exploration (i.e. time spent in the light zone of the Light/Dark Box) and novel object investigation of juveniles indicating an inhibitory role for the juvenile ovary; social approach was unaffected. In contrast, adult ovariectomy and castration (both prepubertal and adult) had no effect on any behavioral measure. Experiment 3 tested whether rearing hamsters in a short day length (SD), which delays puberty in this species, extends the interval of juvenile ovarian inhibition on exploration and novelty seeking. We also tested whether provision of estradiol reverses the effects of prepubertal ovariectomy. Hormonal manipulations and behavioral tests of Experiment 3 were conducted at ages when long day-reared hamsters are adult (as in Experiment 2), but SD-reared hamsters remain reproductively immature. Ovariectomy again increased exploration in the SD-reared juveniles despite the older age of surgery and testing. Estradiol treatment had no effect. These findings reveal a novel role for the juvenile ovary in exploration and novelty seeking that is unlikely to be mediated exclusively by estradiol.
- Protective and therapeutic effects of Pilose antler against kidney deficiency-induced osteoporosis. [Journal Article]
- CMCell Mol Biol (Noisy-le-grand) 2019 Jun 30; 65(5):24-31
- This study was carried out to evaluate the preventive and curative effects of Pilose antler against osteoporosis due to kidney deficiency, and investigate its potential mechanism of action. A model o…
This study was carried out to evaluate the preventive and curative effects of Pilose antler against osteoporosis due to kidney deficiency, and investigate its potential mechanism of action. A model of osteoporosis due to kidney deficiency was established in rats using bilateral ovariectomy. Pilose antler polypeptide (PAP), Pilose antler polysaccharide (PAP'), and their mixture (PAP+PAP') were separately administered to the rats for 12 weeks, with progynova and xianlingubao tablets (XLGB) as the positive control groups. We determined the bone mineral density (BMD) and uterus Index of the rats. Osteoblastic bone metabolism-related indices in serum and bone tissue were measured with ELISA. Western blotting and RT-PCR were used to investigate the protein and mRNA expressions of Bmp-2, Smad1, Smad5, Runx2 in bone tissue. The morphology of bone tissue was determined using immunohistochemical methods. Compared with control group, PAP, PAP', PAP+PAP' increased BMD and regulated bone metabolism indices in serum and bone tissue. Treatment with Pilose antler up-regulated the mNRA and protein expressions of Bmp-2, Smad1, Smad5 and Runx2. Immunohistochemical staining showed that Bmp-2, Smad1, Smad5 and Runx2 were stained brown, indicating that all of them were positive. There were abnormal changes in the protein expressions of Bmp-2, Smad1, Smad5 and Runx2 in bone tissue, which may be an important mechanism underlying the development of kidney deficiency osteoporosis. Moreover, PAP, PAP' and PAP+PAP' had some preventive effects on osteoporosis, probably via the activation of the Bmp-2/Smad1 and Smad5/Runx2 signaling pathways through induction of high expressions of their mRNAs and proteins.
- Luteolin reduces adipose tissue macrophage inflammation and insulin resistance in postmenopausal obese mice. [Journal Article]
- JNJ Nutr Biochem 2019 Jun 20; 71:72-81
- Previously, we showed that loss of ovarian function in mice fed high-fat diet exacerbated insulin resistance and adipose tissue inflammation. In the current study, we tested whether consumption of lu…
Previously, we showed that loss of ovarian function in mice fed high-fat diet exacerbated insulin resistance and adipose tissue inflammation. In the current study, we tested whether consumption of luteolin, an anti-inflammatory flavonoid, could mitigate adipose tissue inflammation and insulin resistance in obese ovariectomized mice. Nine-week-old ovariectomized C57BL/6 mice were fed a low-fat diet, high-fat diet (HFD) or HFD supplemented with 0.005% luteolin (HFD+L) for 16 weeks. Results showed no difference in body weight or fat mass between mice fed HFD+L and those fed HFD. However, luteolin supplementation resulted in lower CD11c+ macrophages in gonadal adipose tissue, as well as a trend toward lower macrophage infiltration. Luteolin supplementation also significantly lowered mRNA expression of inflammatory and M1 markers MCP-1, CD11c, TNF-α and IL-6, while maintaining expression of M2 marker MGL1. Consistent with this, the in vitro luteolin treatment, with or without the presence of estrogen, inhibited lipopolysaccharide-induced polarization of RAW 264.7 cells toward M1 phenotype. We further found that luteolin supplementation protected mice from insulin resistance induced by HFD consumption; this improved insulin resistance was correlated with reductions in CD11c+ adipose tissue macrophages. Taken together, these findings indicate that dietary luteolin supplementation attenuates adipose tissue inflammation and insulin resistance found in mice with loss of ovarian function coupled with an HFD intake, and this effect may be partly mediated through suppressing M1-like polarization of macrophages in adipose tissue. These results have clinical implication in implementing dietary intervention for prevention of metabolic syndrome associated with postmenopause and obesity.
- Oestrogen-deficiency induces bone loss by modulating CD14+ monocyte and CD4+ T cell DR3 expression and serum TL1A levels. [Journal Article]
- BMBMC Musculoskelet Disord 2019 Jul 12; 20(1):326
- CONCLUSIONS: Our results reveals for the first time that loss of oestrogen has a significant effect on DR3; decreasing expression on CD14+ monocytes and increasing expression on CD4+ T cells. These data suggest that while oestrogen-deficiency induced changes in DR3 expression do not affect late post-menopausal bone loss they could potentially have an indirect role in early menopausal bone loss through the modulation of T cell activity.
- Bone protective effects of purified extract from Ruscus aculeatus on ovariectomy-induced osteoporosis in rats. [Journal Article]
- FCFood Chem Toxicol 2019 Jul 09; 132:110668
- Ruscus aculeatus is a source of steroidal saponins that could mimic sex hormones and could help alleviate the risk of fracture in osteoporotic patients. The aim of the present study was to evaluate t…
Ruscus aculeatus is a source of steroidal saponins that could mimic sex hormones and could help alleviate the risk of fracture in osteoporotic patients. The aim of the present study was to evaluate the in vitro effects of an extract from R. aculeatus (ERA) on the proliferation of human osteoblast-like SaOS-2 cell line and to investigate the effects of the ERA administered orally for 10 weeks at three doses (50, 100 and 200 mg/kg) on the bone structure of rats with estrogen deficiency induced by bilateral ovariectomy. Bone turnover markers, hormones, histopathological and radiological disturbances were evidenced in the ovariectomized rats. ERA recovered most of the affected parameters in a dose-dependent manner similar to diosgenin and alendronate used as positive comparators. The main active compounds of ERA (ruscogenin and neoruscogenin) were docked into the Vit. D receptor and oestrogen receptors alpha and beta, and stable complexes were found with binding scores equal to those of estradiol and diosgenin. The findings of this study provide for the first time an insight into the effects of ERA on bone structure and suggest that ERA could be developed as a potential candidate for the prevention of postmenopausal osteoporotic complications.
- Escitalopram Ameliorates Cognitive Impairment in D-Galactose-Injected Ovariectomized Rats: Modulation of JNK, GSK-3β, and ERK Signalling Pathways. [Journal Article]
- SRSci Rep 2019 Jul 11; 9(1):10056
- Though selective serotonin reuptake inhibitors (SSRIs) have been found to increase cognitive performance in some studies on patients and animal models of Alzheimer's disease (AD), other studies have …
Though selective serotonin reuptake inhibitors (SSRIs) have been found to increase cognitive performance in some studies on patients and animal models of Alzheimer's disease (AD), other studies have reported contradictory results, and the mechanism of action has not been fully described. This study aimed to examine the effect of escitalopram, an SSRI, in an experimental model of AD and to determine the involved intracellular signalling pathways. Ovariectomized rats were administered D-galactose (150 mg/kg/day, i.p) over ten weeks to induce AD. Treatment with escitalopram (10 mg/kg/day, p.o) for four weeks, starting from the 7th week of D-galactose injection, enhanced memory performance and attenuated associated histopathological changes. Escitalopram reduced hippocampal amyloid β 42, β-secretase, and p-tau, while increasing α-secretase levels. Furthermore, it decreased tumor necrosis factor-α, nuclear factor-kappa B p65, and NADPH oxidase, while enhancing brain-derived neurotrophic factor, phospho-cAMP response element binding protein, and synaptophysin levels. Moreover, escitalopram diminished the protein expression of the phosphorylated forms of c-Jun N-terminal kinase (JNK)/c-Jun, while increasing those of phosphoinositide 3-kinase (PI3K), protein kinase B (Akt), glycogen synthase kinase-3β (GSK-3β), extracellular signal-regulated kinase (ERK) and its upstream kinases MEK and Raf-1. In conclusion, escitalopram ameliorated D-galactose/ovariectomy-induced AD-like features through modulation of PI3K/Akt/GSK-3β, Raf-1/MEK/ERK, and JNK/c-Jun pathways.
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- High Fat Diet Triggers a Reduction in Body Fat Mass in Female Mice Deficient for Utx demethylase. [Journal Article]
- SRSci Rep 2019 Jul 11; 9(1):10036
- Obesity increases the risk of metabolic disorders like diabetes mellitus and dyslipidemia. However, how metabolic status is sensed and regulates cellular behavior is unclear. Utx is an H3K27 demethyl…
Obesity increases the risk of metabolic disorders like diabetes mellitus and dyslipidemia. However, how metabolic status is sensed and regulates cellular behavior is unclear. Utx is an H3K27 demethylase that influences adipocyte function in vitro. To examine its role in vivo, we generated mice lacking Utx in adipocytes (UtxAKO). Although all UtxAKO mice grew normally on a normal chow diet (NCD), female UtxAKO mice on a high fat diet (HFD) showed striking reductions in body fat compared to control mice (Ctrl). Gene expression profiling of adipose tissues of HFD-fed UtxAKO female mice revealed decreased expression of rate-limiting enzymes of triacylglycerol synthesis but increased expression of those of cholesterol/steroid hormone synthesis. Moreover, these animals resisted adiposity induced by ovariectomy and exhibited increased estrogen in visceral adipose tissues. Thus, upon HFD feeding, Utx regulates lipid metabolism in adipose tissues by influencing the local hormonal microenvironment. Conversely, Utx deficiency skews lipid catabolism to enhance cholesterol/steroid hormone production and repress obesity.