Viscoelastic Coagulation Monitor (VCMVet) Reference Intervals and Sex Differences in Mature Adult Mice

2021 ◽  
pp. 1-8
Author(s):  
Robert R. Rigor ◽  
Linda M. Schutzman ◽  
Joseph M. Galante ◽  
Ian E. Brown
Keyword(s):  
Sex Differences ◽  
Molecular Mechanisms ◽  
Alpha Angle ◽  
Reference Intervals ◽  
Coagulation Test ◽  
Mature Adult ◽  
Male And Female ◽  
Female Mice ◽  
Adult Mice ◽  
Coagulation Status

<b><i>Introduction:</i></b> Viscoelastic coagulation tests are useful to assess coagulation status in the clinical setting and to aid in understanding underlying pathophysiological mechanisms that affect coagulation status. Such tests also are useful for coagulation research. Because mouse models are widely used to study molecular mechanisms in fine detail, a simple viscoelastic coagulation test requiring small blood volumes would be convenient for such studies in mice. <b><i>Methods:</i></b> We tested viscoelastic coagulation properties of normal healthy adult mice using a novel veterinary clinical point-of-care device, Viscoelastic Coagulation Monitor (VCM Vet™; Entegrion Corp.). Fresh whole blood was collected from 63 healthy mature adult C57 black 6N mice, with ultimately 54 mice, equal numbers of male and females, used to determine reference intervals (RIs) for VCM test parameters. <b><i>Results:</i></b> RIs were determined for equal numbers of male and female mice: clot time: 43.0–353.0 s; clot formation time: 49.4–137.6 s; alpha angle: 54.4–62.2°; A10: 25.0–49.6 VCM units; A20: 31.0–56.5 VCM units; maximum clot firmness: 37.6–62.8 VCM units; Lysis Index 30 (Li30): 99.8–100.0%; and Li45: 99.7–100.0%. Significant differences were found between male and female subgroups, where females had higher mean A10 and A20 and median MCF values, indicating greater clot firmness in female versus male mice. <b><i>Conclusion:</i></b> VCM Vet is a feasible viscoelastic coagulation test device for studies with mature adult mice, including studying inherent sex differences in coagulation parameters. Inherent differences in coagulability of male and female mice warrant further investigation to determine if such differences underlie greater coagulopathic, hemorrhagic, or thromboembolic risk during trauma or other pathophysiologic conditions.

scholarly journals The role of the cannabinoid system in fear memory and extinction in male and female mice

2021 ◽  
Author(s):  
Ikumi Mizuno ◽  
Shingo Matsuda ◽  
Suguru Tohyama ◽  
Akihiro Mizutani
Keyword(s):  
Sex Differences ◽  
Molecular Mechanisms ◽  
Acid Amide ◽  
Fear Memory ◽  
Fear Extinction ◽  
Male And Female ◽  
Contextual Fear ◽  
Contextual Fear Memory ◽  
Female Mice

The prevalence of post-traumatic stress disorder (PTSD) is higher in women than in men. Among both humans and mice, females exhibit higher resistance to fear extinction than males, suggesting that differences between sexes in processes of fear extinction are involved in the pathophysiology of such fear-related diseases. Sex differences in molecular mechanisms for fear memory and extinction are unclear. The cannabinoid (CB) system is well known to be involved in fear memory and extinction, but this involvement is based mainly on experiments using male rodents. It has been unclear whether there are sex differences in the role of the CB system in fear memory and extinction. To explore the possibility of such differences, we investigated the effects of pharmacological manipulations of the CB system on the retrieval and extinction of contextual fear memory in male and female mice. WIN55,212-2, a CB receptor (CBR) agonist, augmented the retrieval of fear memory in both sexes, but SR141716 (a CB1R antagonist) did not affect it in either sex. An enhancement of 2-arachidonylglycerol (2-AG, one of the two major endocannabinoids) via JZL184 [an inhibitor of the 2-AG hydrolase monoacylglycerol lipase (MAGL)], augmented the retrieval of fear memory through the activation of CB1R but not CB2R in female mice. In contrast, the enhancement of N-arachidonylethanolamine (AEA, the other major endocannabinoid) via URB597, an inhibitor of an AEA hydrolase (fatty acid amide hydrolase-1) did not show any effects on the retrieval or extinction of fear memory in either sex. WIN55,212-2, SR141716, and JZL184 inhibited fear extinction irrespective of sex. These results suggest that although the role of CB1R in the retrieval and extinction of contextual fear memory is common among males and females, the effects of an increase in the 2-AG level on the retrieval of contextual fear memory differ between the sexes.

scholarly journals Androgen sulphate formation in male and female mice

1969 ◽  
Vol 115 (3) ◽  
pp. 489-493
Author(s):  
D A Lewis
Keyword(s):  
Sex Differences ◽  
Sulphuric Acid ◽  
Female Rats ◽  
Dehydroepiandrosterone Sulphate ◽  
Male And Female ◽  
Female Mice ◽  
Liver Slices ◽  
Rats And Mice

1. After the administration of large doses of androsterone, epiandrosterone, dehydroepiandrosterone and testosterone to mice, females excreted more of the dose conjugated with sulphuric acid than did males. 2. Liver slices from female mice conjugated androgens with sulphuric acid to a greater extent than did slices from males. 3. Sulphotransferase preparations from livers of female rats and mice catalysed the formation of dehydroepiandrosterone sulphate at a faster rate than preparations from livers of the male animals. 4. A possible explanation for the observed sex differences is discussed.

Sex Differences in the Relation Between Frailty and Endothelial Dysfunction in Old Mice

2021 ◽  
Author(s):  
Jazmin A Cole ◽  
Mackenzie N Kehmeier ◽  
Bradley R Bedell ◽  
Sahana Krishna Kumaran ◽  
Grant D Henson ◽  
...  
Keyword(s):  
Sex Differences ◽  
Endothelial Function ◽  
Vascular Function ◽  
Mesenteric Artery ◽  
Frailty Index ◽  
Mesenteric Arteries ◽  
Male Mice ◽  
Male And Female ◽  
Female Mice ◽  
Age Related

Abstract Vascular endothelial function declines with age on average, but there is high variability in the magnitude of this decline within populations. Measurements of frailty, known as frailty index (FI), can be used as surrogates for biological age, but it is unknown if frailty relates to the age-related decline in vascular function. To examine this relation, we studied young (4-9 months) and old (23-32 months) C57BL6 mice of both sexes. We found that FI was greater in old compared with young mice, but did not differ between old male and female mice. Middle cerebral artery (MCA) and mesenteric artery endothelium-dependent dilation (EDD) also did not differ between old male and female mice; however, there were sex differences in the relations between FI and EDD. For the MCA, FI was inversely related to EDD among old female mice, but not old male mice. In contrast, for the mesenteric artery, FI was inversely related to EDD among old male mice, but not old female mice. A higher FI was related to a greater improvement in EDD with the superoxide scavenger TEMPOL in the MCAs for old female mice and in the mesenteric arteries for old male mice. FI related to mesenteric artery gene expression negatively for extracellular superoxide dismutase (Sod3) and positively for interleukin-1β (Il1b). In summary, we found that the relation between frailty and endothelial function is dependent on sex and the artery examined. Arterial oxidative stress and pro-inflammatory signaling are potential mediators of the relations of frailty and endothelial function.

Abstract T P210: Splenectomy Attenuates Sex Differences in Infarct Volume Following Experimental Stroke in Mice

Stroke ◽  
2014 ◽  
Vol 45 (suppl_1) ◽  
Author(s):  
Jianming Wang ◽  
Sheetal Bodhankar ◽  
Halina Offner ◽  
Stephanie J Murphy
Keyword(s):  
Sex Differences ◽  
Blood Glucose ◽  
Brain Injury ◽  
Infarct Volume ◽  
Blood Gases ◽  
Experimental Stroke ◽  
Ischemic Brain Injury ◽  
Ischemic Brain ◽  
Male And Female ◽  
Female Mice

It is now increasingly clear that human stroke can have other serious consequences besides brain damage that can impact on patient survival and recovery. For example, many stroke patients succumb to CNS injury-induced immunodepression and fatal infections. Our prior work suggests that evolving cerebral ischemic injury elicits a cycle of injury from brain-to-spleen-to-brain that is strongly influenced by sex. We determined if splenic immunocytes are important in contributing to sex differences in post-ischemic brain injury. Male and female C57BL/6J mice were splenectomized 14 days before experimental stroke. Male and female mice with or without splenectomy (n=9-10 per group) then underwent 60 min of middle cerebral artery occlusion (MCAO) via intraluminal filament. Laser-Doppler flowmetry (LDF) was used to monitor cortical perfusion. All mice were euthanized and brains collected at 96 hours of reperfusion. Infarct volume (% corrected contralateral structure) was determined by image analysis of coronal brain slices stained with 2,3,5-triphenyltetrazolium chloride. Mean arterial blood pressure (MABP), blood gases (pH, P a O 2 , P a CO 2 ), and blood glucose were measured at 30 min MCAO and at 15 min of reperfusion in separate groups of male and female mice with or without splenectomy (n=5 per group). Relative LDF changes (% baseline), MABP, blood gases, and blood glucose during and after MCAO were comparable among the experimental groups. We observed that infarct volume in females (cortex, 41±4%; striatum, 55±6%) was smaller ( P <0.05) compared to males (cortex, 52±3%; striatum, 75±3%) at 96 hours of reperfusion. However, no differences (cortex, P =0.313; striatum, P =0.601) in infarct volume were seen between splenectomized male (cortex, 43±4%; striatum, 51±7%) and female (cortex, 38±4%; striatum, 46±5%) mice. Our data suggest that removal of all splenocyte lineages via splenectomy attenuates sex differences in post-ischemic brain injury. Future studies will evaluate the role of different splenic immunocyte subsets, such as T or B lymphocytes, on male vs. female ischemic brain outcomes. This study was supported by National Institutes of Health grant NS076013.

scholarly journals CBMT-45. SEX-SPECIFIC METABOLIC ADAPTIONS IN GLIOBLASTOMA

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi42-vi43
Author(s):  
Jasmin Sponagel ◽  
Shanshan Zhang ◽  
Prakash Chinnaiyan ◽  
Joshua Rubin ◽  
Joseph Ippolito
Keyword(s):  
Sex Differences ◽  
Sexual Dimorphism ◽  
Molecular Mechanisms ◽  
Treatment Strategies ◽  
Tca Cycle ◽  
Metabolic Reprogramming ◽  
Mitochondrial Activity ◽  
Male And Female ◽  
Glutamine Deprivation ◽  
Novel Treatment Strategies

Abstract Glioblastoma (GBM) is the most common and aggressive brain tumor in adults. GBM occurs more commonly in males, but female patients survive significantly longer. Understanding the molecular mechanisms that underlie those sex differences could support novel treatment strategies. In this regard, we found that male and female GBM patient samples differ in their metabolite abundance and that male patients exhibit a significantly higher abundance of TCA cycle metabolites. We confirmed those findings in a murine model of GBM, which has previously yielded important insights into sexual dimorphism in GBM. Strikingly, sex differences in TCA cycle flux were entirely driven by glutamine flux, not glucose flux, suggesting a sex-specific role for glutamine in GBM. Metabolic manipulation through glutamine deprivation resulted in a greater growth inhibition in male GBM cells. Glutamine itself can be utilized for anabolic reactions or it can be converted to glutamate by glutaminase. Only male GBM cells were sensitive to pharmacological glutaminase inhibition with BPTES or CB-839, suggesting that male GBM cells are glutamate dependent while female GBM cells are not. Concordantly, we found significantly higher glutaminase levels in male GBM cells. Furthermore, we found that numerous metabolites (including NADH, ATP, and glutathione) involved in cellular processes downstream of glutamate were more abundant in male GBM cells. In contrast, female GBM cells were resistant to low glutamine conditions and glutaminase inhibitors unless glutamine-synthase activity was disrupted, suggesting that glutamine synthesis might play a more prominent role in female GBM. Together, these data indicate that male and female GBM differ in their metabolic adaptions. Male GBM utilize glutamate to fuel the TCA cycle and mitochondrial activity while female GBM synthesize and utilize glutamine itself. This sexual dimorphism in metabolic reprogramming reveals novel sex specific metabolic targets for GBM and underlines the importance of considering sex in metabolic targeting approaches.

scholarly journals Sex differences in renal and metabolic responses to a high-fructose diet in mice

2015 ◽  
Vol 308 (5) ◽  
pp. F400-F410 ◽  
Author(s):  
Nikhil Sharma ◽  
Lijun Li ◽  
C. M. Ecelbarger
Keyword(s):  
Sex Differences ◽  
Glucose Transporter ◽  
Collecting Duct ◽  
Urine Volume ◽  
Thick Ascending Limb ◽  
Male Mice ◽  
Male And Female ◽  
Female Mice ◽  
High Fructose Diet ◽  
High Fructose

High fructose intake has been associated with increased incidences of renal disease and hypertension, among other pathologies. Most fructose is cleared by the portal system and metabolized in the liver; however, systemic levels of fructose can rise with increased consumption. We tested whether there were sex differences in the renal responses to a high-fructose diet in mice. Two-month-old male and female C57BL6/129/SV mice ( n = 6 mice per sex per treatment) were randomized to receive control or high-fructose (65% by weight) diets as pelleted chow ad libitum for 3 mo. Fructose feeding did not significantly affect body weight but led to a 19% and 10% increase in kidney weight in male and female mice, respectively. In male mice, fructose increased the expression (∼50%) of renal cortical proteins involved in metabolism, including glucose transporter 5 (facilitative fructose transporter), ketohexokinase, and the insulin receptor (β-subunit). Female mice had lower basal levels of glucose transporter 5, which were unresponsive to fructose. However, female mice had increased urine volume and plasma K+ and decreased plasma Na+ with fructose, whereas male mice were less affected. Likewise, female mice showed a two- to threefold reduction in the expression Na+-K+-2Cl− cotransporter 2 in the thick ascending limb and aquaporin-2 in the collecting duct with fructose relative to female control mice, whereas male mice had no change. Overall, our results support greater proximal metabolism of fructose in male animals and greater distal tubule/collecting duct (electrolyte homeostasis) alterations in female animals. These sex differences may be important determinants of the specific nature of pathologies that develop in association with high fructose consumption.

scholarly journals Sex Differences in Nociceptor Translatomes Contribute to Divergent Prostaglandin Signaling in Male and Female Mice

2020 ◽  
Author(s):  
Diana Tavares-Ferreira ◽  
Pradipta R. Ray ◽  
Ishwarya Sankaranarayanan ◽  
Galo L. Mejia ◽  
Andi Wangzhou ◽  
...  
Keyword(s):  
Sex Differences ◽  
Male And Female ◽  
Female Mice

scholarly journals Clinically Important sex differences in GBM biology revealed by analysis of male and female imaging, transcriptome and survival data

2017 ◽  
Author(s):  
Wei Yang ◽  
Nicole M. Warrington ◽  
Sara J. Taylor ◽  
Eduardo Carrasco ◽  
Kyle W. Singleton ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Sex Differences ◽  
Survival Data ◽  
Molecular Mechanisms ◽  
Quantitative Imaging ◽  
Outcome Data ◽  
Integrin Signaling ◽  
Chemotherapy Sensitivity ◽  
Male And Female

AbstractSex differences in the incidence and outcome of human disease are broadly recognized but in most cases not adequately understood to enable sex-specific approaches to treatment. Glioblastoma (GBM), the most common malignant brain tumor, provides a case in point. Despite well-established differences in incidence, and emerging indications of differences in outcome, there are few insights that distinguish male and female GBM at the molecular level, or allow specific targeting of these biological differences. Here, using a quantitative imaging-based measure of response, we found that temozolomide chemotherapy is more effective in female compared to male GBM patients. We then applied a novel computational algorithm to linked GBM transcriptome and outcome data, and identified novel sex-specific molecular subtypes of GBM in which cell cycle and integrin signaling were identified as the critical determinants of survival for male and female patients, respectively. The clinical utility of cell cycle and integrin signaling pathway signatures was further established through correlations between gene expression and in vitro chemotherapy sensitivity in a panel of male and female patient-derived GBM cell lines. Together these results suggest that greater precision in GBM molecular subtyping can be achieved through sex-specific analyses, and that improved outcome for all patients might be accomplished via tailoring treatment to sex differences in molecular mechanisms.One Sentence SummaryMale and female glioblastoma are biologically distinct and maximal chances for cure may require sex-specific approaches to treatment.

scholarly journals Prepubertal gonadectomy reveals sex differences in approach-avoidance behavior in adult mice

2019 ◽  
Author(s):  
Kristen Delevich ◽  
Christopher Hall ◽  
Josiah R. Boivin ◽  
David Piekarski ◽  
Yuting Zhang ◽  
...  
Keyword(s):  
Sex Differences ◽  
Adult Male ◽  
Gonadal Hormones ◽  
Gonadal Hormone ◽  
Opposite Pattern ◽  
Male And Female ◽  
Female Mice ◽  
Puberty Onset ◽  
Approach Avoidance ◽  
Foraging Task

AbstractAdolescence is a developmental period that is associated with physical, cognitive, and affective maturation and a time when sex biases in multiple psychiatric diseases emerge. While puberty onset marks the initiation of adolescence, it is unclear whether the pubertal rise in gonadal hormones generates sex differences in approach-avoidance behaviors that may impact psychiatric vulnerability. To examine the influence of peripubertal gonadal hormone exposure on adult behavior, we removed the gonads or performed sham surgery in male and female mice just prior to puberty onset and assessed performance in an odor-guided foraging task and anxiety-related behaviors in adulthood. We observed no significant sex differences in foraging or anxiety-related behaviors between intact adult male and female mice but found significant differences between adult male and female mice that had been gonadectomized (GDX) prior to puberty. GDX males failed to acquire the odor-guided foraging task, showed reduced locomotion, and exhibited increased anxiety-like behavior, while GDX females showed the opposite pattern of behavior. These data suggest that similar approach-avoidance phenotypes are achieved in male and female mice via different mechanisms mediated by the sex-specific hormonal milieus during pubertal maturation.

scholarly journals Ablation of AMPK-related kinase MPK38/MELK leads to male-specific obesity in aged mature adult mice

2020 ◽  
Author(s):  
Ada Admin ◽  
Hyun-A Seong ◽  
Hyunjung Ha
Keyword(s):  
Leucine Zipper ◽  
Physiological Role ◽  
Serum Testosterone ◽  
Standard Diet ◽  
Mature Adult ◽  
Female Mice ◽  
Adult Mice ◽  
Serum Luteinizing Hormone ◽  
Age Related ◽  
The Stability

Murine protein serine-threonine kinase 38 (MPK38)/maternal embryonic leucine zipper kinase (MELK) is implicated in diverse biological processes, including the cell cycle, apoptosis, and tumorigenesis; however, its physiological role is unknown. Using mice lacking MPK38 (MPK38<sup>−/−</sup>), we found that MPK38<sup>−/−</sup> male, but not female, mice (7 months of age) became obese while consuming a standard diet, displayed impairments in metabolism and inflammation, became obese than wild-type mice while consuming a high-fat diet (HFD), and exhibited no castration/testosterone (T) replacement-induced metabolic changes. The adenoviral restoration of MPK38 ameliorated the obesity-induced adverse metabolic profile of the obese male, but not female, mice. Seven-month-old MPK38<sup>−/−</sup> males displayed typical post-castration concentrations of serum testosterone with an accompanying decrease in serum luteinizing hormone (LH) levels, suggesting a role for MPK38 in the age-related changes in serum testosterone in aged mature adult male mice. The stability and activity of MPK38 were increased by dihydrotestosterone (DHT) but reduced by estradiol (E2). These findings suggest MPK38 as a therapeutic target for obesity-related metabolic disorders in males.

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