Cardiac contraction, calcium transients, and myofilament calcium sensitivity fluctuate with the estrous cycle in young adult female mice

2014 ◽  
Vol 306 (7) ◽  
pp. H938-H953 ◽  
Author(s):  
Jennifer K. MacDonald ◽  
W. Glen Pyle ◽  
Cristine J. Reitz ◽  
Susan E. Howlett
Keyword(s):  
Estrous Cycle ◽  
Action Potentials ◽  
Ventricular Myocytes ◽  
Fold Increase ◽  
Reproductive Hormones ◽  
Cardiac Contraction ◽  
Estrous Cycles ◽  
Female Mice ◽  
Ec Coupling ◽  
The Impact

This study established conditions to induce regular estrous cycles in female C57BL/6J mice and investigated the impact of the estrous cycle on contractions, Ca2+ transients, and underlying cardiac excitation-contraction (EC)-coupling mechanisms. Daily vaginal smears from group-housed virgin female mice were stained to distinguish estrous stage (proestrus, estrus, metestrus, diestrus). Ventricular myocytes were isolated from anesthetized mice. Contractions and Ca2+ transients were measured simultaneously (4 Hz, 37°C). Interestingly, mice did not exhibit regular cycles unless they were exposed to male pheromones in bedding added to their cages. Field-stimulated myocytes from mice in estrus had larger contractions (∼2-fold increase), larger Ca2+ transients (∼1.11-fold increase), and longer action potentials (>2-fold increase) compared with other stages. Larger contractions and Ca2+ transients were not observed in estrus myocytes voltage-clamped with shorter action potentials. Voltage-clamp experiments also demonstrated that estrous stage had no effect on Ca2+ current, EC-coupling gain, diastolic Ca2+, sarcoplasmic reticulum (SR) Ca2+ content, or fractional release. Although contractions were largest in estrus, myofilament Ca2+ sensitivity was lowest (EC50 values ∼1.15-fold higher) in conjunction with increased phosphorylation of myosin binding protein C in estrus. Contractions were enhanced in ventricular myocytes from mice in estrus because action potential prolongation increased SR Ca2+ release. These findings demonstrate that cyclical changes in reproductive hormones associated with the estrous cycle can influence myocardial electrical and contractile function and modify Ca2+ homeostasis. However, such changes are unlikely to occur in female mice housed in groups under conventional conditions, since these mice do not exhibit regular estrous cycles.

Role of voltage-sensitive release mechanism in depression of cardiac contraction in myopathic hamsters

1999 ◽  
Vol 277 (5) ◽  
pp. H1690-H1700 ◽  
Author(s):  
Susan E. Howlett ◽  
Wei Xiong ◽  
Cindy L. Mapplebeck ◽  
Gregory R. Ferrier
Keyword(s):  
Voltage Clamp ◽  
Action Potentials ◽  
Ventricular Myocytes ◽  
Cardiac Contraction ◽  
Release Mechanism ◽  
Edge Detector ◽  
Ec Coupling ◽  
Hamster Heart ◽  
Isolated Ventricular Myocytes

We investigated excitation-contraction (EC) coupling in isolated ventricular myocytes from prehypertrophic cardiomyopathic (CM) hamster hearts. Conventional and voltage-clamp recordings were made with high-resistance microelectrodes, and cell shortening was measured with a video-edge detector at 37°C. Contractions were depressed in myocytes from CM hearts, whether they were initiated by action potentials or voltage-clamp steps. As in guinea pig and rat, contraction in hamster myocytes could be triggered by a voltage-sensitive release mechanism (VSRM) or Ca2+-induced Ca2+ release (CICR). Selective activation of these mechanisms demonstrated that the defect in EC coupling was primarily caused by a defect in the VSRM. However, activation and inactivation properties of the VSRM were not altered. When the VSRM was inhibited, the remaining contractions induced by CICR exhibited identical bell-shaped contraction voltage relations in normal and CM myocytes. Inward Ca2+current was unchanged. Thus a defect in the VSRM component of EC coupling precedes the development of hypertrophy and failure in CM hamster heart.

Abstract 1330: Divergent Control of the Mitochondrial Death Gene BNIP3 by Opposing Actions of the Cellular Factors Nuclear Factor kappaB and E2F-1 in Ventricular Myocytes.

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
James Shaw ◽  
Natalia Yurkova ◽  
Kelly Regula ◽  
Tong Zhang ◽  
Floribeth Aguilar ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Death ◽  
Dna Binding ◽  
Gene Transcription ◽  
Ventricular Myocytes ◽  
Fold Increase ◽  
Genetic Ablation ◽  
The Impact ◽  
Chip Analysis ◽  
In Cells

The hypoxia-inducible death factor Bnip3 is known to provoke mitochondrial perturbations and cell death of ventricular myocytes. The transcriptional control processes that govern Bnip3 gene expression under basal and inducible conditions remain cryptic. Sequence analysis of the Bnip3 promoter revealed the presence of distinct but overlapping DNA binding elements for the cell cycle factor E2F-1 and cellular factor NF-κB. Previously, we reported a survival role for NF-κB in ventricular myocytes. As a step toward elucidating the regulation of Bnip3 gene expression in ventricular myocytes, we tested the impact of E2F-1 and NF-κB on basal and inducible expression of Bnip3. A 2.0 fold increase in Bnip3 gene transcription was observed in cells expression wild type E2F-1 but not in cells expressing an E2F-1 mutant defective for DNA binding. Interestingly, basal Bnip3 gene transcription was increased by 2.5 fold in myocytes rendered defective for NF-κB activation with a non-phosphorylatable form of IκBα. Importantly, genetic ablation of E2F-1 inhibited basal and inducible Bnip3 transcription in NF-κB defective cells. Expression of the p65 subunit of NF-κB in NF-κB defective cells inhibited E2F-1 mediated Bnip3 transcription. Western blot analysis of cardiac cell lysate revealed that p65 NF-κB immunoprecipitated with E2F-1. ChIP analysis of the Bnip3 promoter indicated that the p65 NF-κB bound DNA under normoxic conditions. During hypoxia E2F-1 activity increased where as p65 NF-κB protein levels were decreased. ChIP analysis revealed increased binding of E2F-1 to the Bnip3 promoter during hypoxia which coincided with a 3.5 fold increase in Bnip3 gene transcription. IKKβ mediated activation of NF-κB activation abrogated hypoxia-induced E2F-1 binding to the Bnip3 promoter and Bnip3 gene transcription. To our knowledge our data provide the first direct evidence that a novel relationship exists between p65 NF-κB and E2F-1 for basal and hypoxia-inducible regulation of the Bnip3 promoter. Furthermore, our data highlight a novel survival pathway by which NF-κB averts hypoxia - induced cell death by antagonizing the E2F-1 dependent transcription of Bnip3 in ventricular myocytes.

scholarly journals Pengendalian Folikulogenesis Ovarium dengan Pemberian Ekstrak Biji Kapas

2017 ◽  
Vol 35 (1) ◽  
pp. 71
Author(s):  
Siska Adelya Ramadhani ◽  
Iman Supriatna ◽  
Ni Wayan Kurniani Karja ◽  
Adi Winarto
Keyword(s):  
Body Weight ◽  
Estrous Cycle ◽  
Treatment Period ◽  
Cotton Seed ◽  
Follicular Development ◽  
Giemsa Staining ◽  
Vaginal Smear ◽  
Estrous Cycles ◽  
Dose Treatment ◽  
Female Mice

Gosipol is a substances contained in extracted cotton seed which is thought to have the antifertility ability therefore it is often used as a herbal contraceptive. The aim of this study were to assess the folliculogenesis in mice after administrated with cottonseed extract. 60 female mice strain DDY which was 14-15 weeks old and 30-35 g body weight were divided into five groups and given cottonseed extract each 0; 1,5; 2,1 and 2,7 g/kg BW for 5, 10, 15, 24, and 24 + 10 days (without cottonseed treatment). At the end of the treatment period, mice was euthanasia to observe follicular development histomorphology (each three mice of each treatment). Mice estrous status were evaluated based on the description of the vaginal smear cells with Giemsa staining. The results showedthat the number of developing follicles was low (P < 0.05) compared with control after 5 days cottonseed extract administration at dose 2,7 g/kg BW that were 23 ± 3,6. At dose 1,5 and 2,1 g/kg BW the number of follicles was low after 24 days that were 25 ± 10,4 and 27 ± 3,5. Recovery effects of follicle number after cottonseed extract administration for 24 days was the best at a dose of 1,5 g/kg BW. Prolonge of estrous cycle occured in mice which were administrated the cottonseed extract of at all dose treatment. In conclusion, although the decrease in the number of developing follicles and prolonge of estrous cycles occurred after cottonseed extract administration, but these effects are reversible after the administration ended.

scholarly journals The impact of chronic restraint stress on the estrous cycle in NMRI female mice

2021 ◽  
Vol 72 (1) ◽  
pp. 6-11
Author(s):  
Jelena Ristić ◽  
Damir Bogdan ◽  
Pavle Banović
Keyword(s):  
Menstrual Cycle ◽  
Estrous Cycle ◽  
Chronic Stress ◽  
Restraint Stress ◽  
Adaptation Period ◽  
Chronic Restraint Stress ◽  
Nmri Mice ◽  
Female Mice ◽  
The Impact ◽  
Experimental Group

Introduction: Stress represents a set of reactions in the organism activated by external factors. In order to maintain homeostasis and protect the organism, numerous mechanisms for adaptation to stress evolved. Stressors that act in short-term period cause acute stress reaction with generally positive effect on organism. When the stressor persists, and the organism fails to respond to the challenge, chronic stress develops, leading to pathological conditions, such as women's menstrual cycle disorders. Aim: To examine the impact of chronic restraint stress on the estrous cycle in NMRI female mice. Material and methods: A number of 12 mature female NMRI mice were randomly divided into control (n = 6) and experimental (n = 6) group. The induction of stress was performed for the experimental group by using restrain chambers 2 hours daily in 14 days. From the beginning of the experiment, vaginal lavages were taken from all mice for making smears that were analyzed to determine estrous cycle stages. For analysis of chronic stress effect, the frequency of estrus stages alternation observed in experimental group compared to control was examined. Results: The estrous cycle was observed and divided into proestrus, estrus, metestrus and diestrus. During the adaptation period, prolonged diestrus was dominantly present in both groups. When stress was induced, in the experimental group animals the absence of diestrus stage and oscillation to other stages was obseved, in contrast to the control group, where the diestus stage was frequently observed. Frequency of diestrus stage deviation in stressed animals was shown to be statistically significant (p < 0.01) when compared to control. Conclusion: The induction of chronic restraint stress in female NMRI mice leads to the alternation of the estrous cycle. Considering the fact that NMRI female mice share the similar hormonal regulation of the estrous cycle with women's menstrual cycle, they could present a solid model for studying women's reproductive disorders.

scholarly journals Fluoxetine effects on behavior and adult hippocampal neurogenesis in female C57BL/6J mice across the estrous cycle

2018 ◽  
Author(s):  
Christine N. Yohn ◽  
Sophie Shifman ◽  
Alexander Garino ◽  
Emma Diethorn ◽  
Leshya Bokka ◽  
...  
Keyword(s):  
Estrous Cycle ◽  
Antidepressant Treatment ◽  
Hippocampal Neurogenesis ◽  
Adult Hippocampal Neurogenesis ◽  
List Type ◽  
Female Mice ◽  
Chronic Fluoxetine ◽  
Brain And Behavior ◽  
And Behavior ◽  
The Impact

AbstractSome mood disorders, such as major depressive disorder, are more prevalent in women than in men. However, historically preclinical studies in rodents have a lower inclusion rate of females than males, possibly due to the fact that behavior can be affected by the estrous cycle. Several studies have demonstrated that chronic antidepressant treatment can decrease anxiety-like behaviors and increase adult hippocampal neurogenesis in male rodents. However, very few studies have conclusively looked at the effects of antidepressants on behavior and neurogenesis across the estrous cycle in naturally cycling female rodents. Here we analyze the effects of chronic treatment with the selective serotonin reuptake inhibitor (SSRI) fluoxetine (Prozac) on behavior and adult hippocampal neurogenesis in naturally cycling C57BL/6J females across all four phases of the estrous cycle. Interestingly, we find that the effects of fluoxetine on both behavior and adult hippocampal neurogenesis are driven by mice specifically in the estrus or diestrus phases of the estrous cycle. Taken together our data is the first to illustrate the impact of fluoxetine on brain and behavior across all four stages of the murine estrous cycle.HighlightsChronic fluoxetine reduces anxiety-like behaviors in naturally cycling female miceChronic fluoxetine increases adult hippocampal neurogenesis in naturally cycling female miceThe effects of chronic fluoxetine on behavior and adult hippocampal neurogenesis are driven by the estrus and diestrus phases of the estrous cycle

scholarly journals Comparison of cannabidiol to citalopram in targeting fear memory in female mice

2020 ◽  
Vol 2 (1) ◽  
Author(s):  
Zackary T. Montoya ◽  
Amy L. Uhernik ◽  
Jeffrey P. Smith
Keyword(s):  
Sexual Dimorphism ◽  
Fear Conditioning ◽  
Estrous Cycle ◽  
Selective Serotonin Reuptake Inhibitors ◽  
Fear Memory ◽  
Memory Formation ◽  
Post Traumatic Stress ◽  
Female Mice ◽  
Memory Type ◽  
The Impact

Abstract Background Cannabidiol (CBD) and selective serotonin reuptake inhibitors (SSRIs) are currently used to treat post-traumatic stress disorder (PTSD). However, these drugs are commonly studied after dosing just prior to extinction training, and there are gaps in our understanding of how they affect fear memory formation, their comparative effects on various types of memory, and of sexual dimorphisms in effects. Also, more studies involving female subjects are needed to balance the gender-inequality in the literature. Therefore, the purpose of this study was to directly compare the effects of CBD to citalopram in affecting the formation of auditory cued, contextual, and generalized fear memory, and to evaluate how extinction of these different memories was altered by pre-acquisition treatment in female mice. We also evaluated the impact of the estrous cycle on each of these. Methods Auditory-cued trace fear conditioning was conducted shortly after dosing female C57BL/6 mice, with either CBD or citalopram (10 mg/kg each), by pairing auditory tones with mild foot shocks. Auditory-cued, contextual, and generalized fear memory was assessed by measuring freezing responses, with an automated fear conditioning system, 24 h after conditioning. Each memory type was then evaluated every 24 h, over a 4-day period in total, to create an extinction profile. Freezing outcomes were statistically compared by ANOVA with Tukey HSD post hoc analysis, N = 12 mice per experimental group. Evaluation of sexual dimorphism was by comparison to historical data from male mice. Results Auditory cue-associated fear memory was not affected with CBD or citalopram; however, contextual memory was reduced with CBD by 11%, p < 0.05, but not citalopram, and generalized fear memory was reduced with CBD and citalopram, 20% and 22%, respectively, p < 0.05. Extinction learning was enhanced with CBD and citalopram, but, there was considerable memory-type variability between drug effects, with freezing levels reduced at the end of training by 9 to 17% for CBD, and 10 to 12% with citalopram. The estrous cycle did not affect any outcomes. Conclusions Both drugs are potent modifiers of fear memory formation; however, there is considerable divergence in their targeting of different memory types which, overall, could support the use of CBD as an alternative to SSRIs for treating PTSD in females, but not males. A limitation of the study was that it compared data from experiments done at different times to evaluate sexual dimorphism. Overall, this suggests that more research is necessary to guide any therapeutic approach involving CBD.

The Protective Effect of Pre-Moxibustion on Reproductive Hormones Profile of Rats with Tripterygium Glycosides-Induced Ovarian Damage

2020 ◽  
Vol 27 (6) ◽  
pp. 401-409
Author(s):  
Shipeng Zhu ◽  
Yaoshuai Wang ◽  
Xiaoxia Chang ◽  
Huan Chen ◽  
Xun Jin
Keyword(s):  
Protective Effect ◽  
Estrous Cycle ◽  
Ovarian Reserve ◽  
Follicular Development ◽  
Control Model ◽  
Reproductive Hormones ◽  
Female Rats ◽  
Estrous Cycles ◽  
Time Points ◽  
Ovarian Damage

<b><i>Background:</i></b> Acupuncture and moxibustion have been proven to be conducive to improving the ovarian reserve. However, the mechanism of pre-moxibustion on <i>Tripterygium</i> glycosides (TG)-induced ovarian damage has not been previously reported. <b><i>Method:</i></b> Female rats were randomly divided into 5 groups: control, model (75 mg/kg TG, 14 days), preventive moxibustion 1 (PM1, receiving moxibustion for 4 weeks before TG administration), preventive moxibustion 2 (PM2, receiving moxibustion for 2 weeks before TG administration and another 2 weeks during TG administration), and preventive moxibustion 3 (PM3, receiving 4 weeks of moxibustion during TG administration). The estrous cycle of the animal was recorded after TG administration. Rats were sacrificed 14 days after TG administration. The reproductive hormones profiles in serum, ovary, and hypothalamic tissues were analyzed. <b><i>Result:</i></b> Pre-moxibustion could revert abnormal estrous cycles, relieve follicle damage, and improve abnormal secretion of reproductive hormones resulting from ovarian damage. However, both PM2 and PM3 were more effective than PM1. In addition, PM2 disclosed more advantages in regulating reproductive hormones abnormalities, while PM3 performed better in follicular development. <b><i>Conclusion:</i></b> In combination, the findings of this study suggest that pre-moxibustion is effective in protecting the ovary from damage in TG-induced ovarian damage rats. But different time points correspond to different modulation targets and mechanisms.

Cardiac excitation-contraction coupling is altered in myocytes from aged male mice but not in cells from aged female mice

2006 ◽  
Vol 291 (5) ◽  
pp. H2362-H2370 ◽  
Author(s):  
Scott A. Grandy ◽  
Susan E. Howlett
Keyword(s):  
Young Adult ◽  
Ventricular Myocytes ◽  
Female Mice ◽  
Ec Coupling ◽  
Age Related ◽  
Intracellular Ca ◽  
Effects Of Aging ◽  
Cardiac Excitation ◽  
Fractional Shortening ◽  
In Cells

This study characterized age-related alterations in excitation-contraction (EC)-coupling in ventricular myocytes and investigated whether these alterations are affected by the sex of the animal. Voltage-clamp experiments were conducted in myocytes from young adult (∼7 mo) and aged (∼24 mo) male and female mice. Intracellular Ca2+ concentrations and unloaded cell shortening were measured at 37°C with fura-2 and a video edge detector. Fractional shortening and Ca2+ current density were significantly reduced in aged male myocytes compared with those in young adult male cells. In addition, Ca2+ transients were significantly smaller in aged male myocytes. Sarcoplasmic reticulum (SR) content, assessed by rapid application of 10 mM caffeine, declined with age in male myocytes. However, EC coupling gain and fractional release of SR Ca2+ were similar in young adult and aged male cells. In contrast to results in male animals, fractional shortening and Ca2+ current densities were similar in young adult and aged myocytes isolated from female hearts. Furthermore, Ca2+ transient amplitudes were unaffected by age in female cells. Interestingly, SR Ca2+ content was elevated in aged female myocytes, and fractional SR Ca2+ release declined with age in females. However, the gain of EC coupling was not different in myocytes from young adult and aged female mice. These data demonstrate that age-related alterations in EC coupling are more prominent in myocytes from male hearts than in cells from female hearts and suggest that it is important to consider sex as a variable in studies of the effects of aging on cardiac EC coupling.

Novel Applications of Nanotechnology in Controlling HIV and HSV Infections

2020 ◽  
Vol 12 ◽  
Author(s):  
Sai Akilesh M ◽  
Ashish Wadhwani
Keyword(s):  
Drug Delivery ◽  
Viral Infections ◽  
Polymeric Nanoparticles ◽  
Volume Ratio ◽  
Fold Increase ◽  
Multi Drug Resistance ◽  
Health Crisis ◽  
Pharmaceutical Properties ◽  
Simplex Virus ◽  
The Impact

: Infectious diseases have been prevalent since many decades and viral pathogens have caused global health crisis and economic meltdown on a devastating scale. High occurrence of newer viral infections in the recent years, in spite of the progress achieved in the field of pharmaceutical sciences defines the critical need for newer and more effective antiviral therapies and diagnostics. The incidence of multi-drug resistance and adverse effects due to the prolonged use of anti-viral therapy is also a major concern. Nanotechnology offers a cutting edge platform for the development of novel compounds and formulations for biomedical applications. The unique properties of nano-based materials can be attributed to the multi-fold increase in the surface to volume ratio at the nano-scale, tunable surface properties of charge and chemical moieties. Idealistic pharmaceutical properties such as increased bioavailability and retention times, lower toxicity profiles, sustained release formulations, lower dosage forms and most importantly, targeted drug delivery can be achieved through the approach of nanotechnology. The extensively researched nano-based materials are metal and polymeric nanoparticles, dendrimers and micelles, nano-drug delivery vesicles, liposomes and lipid based nanoparticles. In this review article, the impact of nanotechnology on the treatment of Human Immunodeficiency Virus (HIV) and Herpes Simplex Virus (HSV) viral infections during the last decade are outlined.

scholarly journals Characterizing the Role of HMG-CoA Reductase in Aryl Hydrocarbon Receptor-Mediated Liver Injury in C57BL/6 Mice

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Peter Dornbos ◽  
Amanda Jurgelewicz ◽  
Kelly A. Fader ◽  
Kurt Williams ◽  
Timothy R. Zacharewski ◽  
...  
Keyword(s):  
Liver Injury ◽  
Aryl Hydrocarbon Receptor ◽  
Cholesterol Biosynthesis ◽  
Competitive Inhibitor ◽  
Cholesterol Homeostasis ◽  
Hepatic Glycogen ◽  
Alcoholic Fatty Liver ◽  
Female Mice ◽  
Aryl Hydrocarbon ◽  
The Impact

Abstract The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor. The prototypical ligand of the AHR is an environmental contaminant called 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). TCDD exposure is associated with many adverse health outcomes in humans including non-alcoholic fatty liver disease (NAFLD). Previous studies suggest that AHR ligands alter cholesterol homeostasis in mice through repression of genes involved in cholesterol biosynthesis, such as Hmgcr, which encodes the rate-limiting enzyme of cholesterol biosynthesis called 3-hydroxy-3-methyl-glutaryl coenzyme A reductase (HMGCR). In this study, we sought to characterize the impact of HMGCR repression in TCDD-induced liver injury. C57BL/6 mice were exposed to TCDD in the presence or absence of simvastatin, a competitive inhibitor of HMGCR. Simvastatin exposure decreased TCDD-induced hepatic lipid accumulation in both sexes, but was most prominent in females. Simvastatin and TCDD (S + T) co-treatment increased hepatic AHR-battery gene expression and liver injury in male, but not female, mice. In addition, the S + T co-treatment led to an increase in hepatic glycogen content that coincides with heavier liver in female mice. Results from this study suggest that statins, which are amongst the most prescribed pharmaceuticals, may protect from AHR-mediated steatosis, but alter glycogen metabolism and increase the risk of TCDD-elicited liver damage in a sex-specific manner.

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