scholarly journals Chronic Treatment With the ACE Inhibitor Enalapril Attenuates the Development of Frailty and Differentially Modifies Pro- and Anti-inflammatory Cytokines in Aging Male and Female C57BL/6 Mice

2018 ◽  
Vol 74 (8) ◽  
pp. 1149-1157 ◽  
Author(s):  
Kaitlyn Keller ◽  
Alice Kane ◽  
Stefan Heinze-Milne ◽  
Scott A Grandy ◽  
Susan E Howlett
Keyword(s):  
Chronic Treatment ◽  
Ace Inhibitor ◽  
Frailty Index ◽  
Protective Effects ◽  
Aging Male ◽  
Male Mice ◽  
Middle Aged ◽  
Male And Female ◽  
Female Mice ◽  
Anti Inflammatory

Abstract Studies on interventions that can delay or treat frailty in humans are limited. There is evidence of beneficial effects of angiotensin converting enzyme (ACE) inhibitors on aspects related to frailty, such as physical function, even in those without cardiovascular disease. This study aimed to longitudinally investigate the effect of an ACE inhibitor on frailty in aging male and female mice. Frailty was assessed with a clinical frailty index (FI) which quantifies health-related deficits in middle-aged (9–13 months) and older (16–25 months) mice. Chronic treatment with enalapril (30 mg/kg/day in feed) attenuated frailty in middle-aged and older female mice, and older male mice, without a long-term effect on blood pressure. Enalapril treatment resulted in a reduction in the proinflammatory cytokines interleukin (IL)-1α, monocyte chemoattractant protein-1 and macrophage inflammatory protein-1a in older female mice, and an increase in the anti-inflammatory cytokine IL-10 in older male mice compared with control animals. These sex-specific effects on inflammation may contribute to the protective effects of enalapril against frailty. This is the first study to examine the longitudinal effect of an intervention on the FI in mice, and provides preclinical evidence that enalapril may delay the onset of frailty, even when started later in life.

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.

scholarly journals Gender-Specific Response to Isoflurane Preconditioning in Focal Cerebral Ischemia

2007 ◽  
Vol 27 (7) ◽  
pp. 1377-1386 ◽  
Author(s):  
Hideto Kitano ◽  
Jennifer M Young ◽  
Jian Cheng ◽  
Lan Wang ◽  
Patricia D Hurn ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Quantitative Polymerase Chain Reaction ◽  
Specific Response ◽  
Male Mice ◽  
Middle Aged ◽  
Male And Female ◽  
Akt Phosphorylation ◽  
Akt Activation ◽  
Female Mice ◽  
Middle Aged Male

Inhalation anesthetics are effective chemical preconditioning agents in experimental cerebral ischemia. However, previous work has been performed exclusively in male animals. We determined if there is a gender difference in ischemic outcome after isoflurane preconditioning (IsoPC), and if this sex-specific response is linked to differences in Akt phosphorylation or expression of neuronal inducible cell-death putative kinase (NIPK), a negative modulator of Akt activation. Young and middle-aged male and female mice were preconditioned for 4 h with air (sham PC) or 1.0% IsoPC and recovered for 24 h. Cortices were subdissected from preconditioned young male and female mice for measurement of Akt phosphorylation (Western blot) and NIPK mRNA (quantitative polymerase chain reaction). Additional cohorts underwent 2 h of reversible middle cerebral artery occlusion. Lastly, male and female Akt1+/+ and Akt1−/– mice were studied to determine if gender differences in ischemic outcome after IsoPC is Akt1-dependent. Infarction volume was determined at 22 h reperfusion (2,3,5-triphenyltetrazolium chloride). As expected, IsoPC decreased ischemic damage as compared with sham PC in young and middle-aged male mice. In contrast, IsoPC markedly increased infarction in young female mice and had no effect in middle-aged female mice. Cortical phospho-Akt was increased by IsoPC versus sham PC only in male mice. No increase was observed in IsoPC female mice. NIPK mRNA was higher in female mice than in male mice regardless of preconditioning status. Male IsoPC neuroprotection was lost in Akt1-deficient male mice. We conclude that IsoPC is beneficial only in ischemic male brain and that sex differences in IsoPC are mediated through Akt activation and basal NIPK expression.

scholarly journals NPY Deficiency Prevents Postmenopausal Adiposity by Augmenting Estradiol-Mediated Browning

2018 ◽  
Vol 75 (6) ◽  
pp. 1042-1049
Author(s):  
Seongjoon Park ◽  
Erkhembayar Nayantai ◽  
Toshimitsu Komatsu ◽  
Hiroko Hayashi ◽  
Ryoichi Mori ◽  
...  
Keyword(s):  
Body Weight ◽  
Adipose Tissue ◽  
Fat Metabolism ◽  
Male Mice ◽  
Wild Type ◽  
Male And Female ◽  
Female Mice ◽  
Age Related ◽  
Promising Target ◽  
Intracellular Mechanism

Abstract The orexigenic hormone neuropeptide Y (NPY) plays a pivotal role in the peripheral regulation of fat metabolism. However, the mechanisms underlying the effects of sex on NPY function have not been extensively analyzed. In this study, we examined the effects of NPY deficiency on fat metabolism in male and female mice. Body weight was slightly decreased, whereas white adipose tissue (WAT) mass was significantly decreased as the thermogenic program was upregulated in NPY-/- female mice compared with that in wild-type mice; these factors were not altered in response to NPY deficiency in male mice. Moreover, lack of NPY resulted in an increase in luteinizing hormone (LH) expression in the pituitary gland, with concomitant activation of the estradiol-mediated thermogenic program in inguinal WAT, and alleviated age-related modification of adiposity in female mice. Taken together, these data revealed a novel intracellular mechanism of NPY in the regulation of fat metabolism and highlighted the sexual dimorphism of NPY as a promising target for drug development to reduce postmenopausal adiposity.

scholarly journals Gender differences in the response of CD-1 mouse bone to parathyroid hormone: potential role of IGF-I

2006 ◽  
Vol 189 (2) ◽  
pp. 279-287 ◽  
Author(s):  
Yongmei Wang ◽  
Takeshi Sakata ◽  
Hashem Z Elalieh ◽  
Scott J Munson ◽  
Andrew Burghardt ◽  
...  
Keyword(s):  
Gender Differences ◽  
Parathyroid Hormone ◽  
Cortical Bone ◽  
Mineral Apposition Rate ◽  
Mrna Levels ◽  
Male Mice ◽  
Bone Formation Rate ◽  
Male And Female ◽  
Female Mice ◽  
Igf I

Parathyroid hormone (PTH) exerts both catabolic and anabolic actions on bone. Studies on the skeletal effects of PTH have seldom considered the effects of gender. Our study was designed to determine whether the response of mouse bone to PTH differed according to sex. As a first step, we analyzed gender differences with respect to bone mass and structural properties of 4 month old PTH treated (80 μg/kg per day for 2 weeks) male and female CD-1 mice. PTH significantly increased fat free weight/body weight, periosteal bone formation rate, mineral apposition rate, and endosteal single labeling surface, while significantly decreasing medullary area in male mice compared with vehicle treated controls, but induced no significant changes in female mice. We then analyzed the gender differences in bone marrow stromal cells (BMSC) isolated from 4 month old male and female CD-1 mice following treatment with PTH (80 μg/kg per day for 2 weeks). PTH significantly increased the osteogenic colony number and the alkaline phosphatase (ALP) activity (ALP/cell) by day 14 in cultures of BMSCs from male and female mice. PTH also increased the mRNA level of receptor activator of nuclear factor κB ligand in the bone tissue (marrow removed) of both females and males. However, PTH increased the mRNA levels of IGF-I and IGF-IR only in the bones of male mice. Our results indicate that on balance a 2-weeks course of PTH is anabolic on cortical bone in this mouse strain. These effects are more evident in the male mouse. These differences between male and female mice may reflect the greater response to PTH of IGF-I and IGF-IR gene expression in males enhancing the anabolic effect on cortical bone.

scholarly journals Reevaluation of Hepatocellular Neoplasms in CD-1 Mice from a 2-year Oral Carcinogenicity Study with Permethrin

2018 ◽  
Vol 47 (1) ◽  
pp. 11-17 ◽  
Author(s):  
Erin M. Quist ◽  
Gary A. Boorman ◽  
John M. Cullen ◽  
Robert R. Maronpot ◽  
Amera K. Remick ◽  
...  
Keyword(s):  
Chronic Toxicity ◽  
Expert Panel ◽  
Biological Significance ◽  
Male Mice ◽  
Male And Female ◽  
Female Mice ◽  
Carcinogenicity Study ◽  
Dose Dependent Increase ◽  
Dose Dependent ◽  
The Continuum

A 24-month oral carcinogenicity study of permethrin was conducted by feeding male and female CD-1 mice diets containing concentrations of 0, 20, 500, and 2,000 ppm of permethrin (males) or 0, 20, 2,500, and 5,000 ppm of permethrin (females). After approximately two years on study, surviving mice were sacrificed for the evaluation of chronic toxicity and/or carcinogenicity. An expert panel of pathologists was convened as a Pathology Working Group (PWG) to review coded liver histology sections from male and female mice and to classify all liver neoplasms according to current nomenclature and diagnostic criteria guidelines. The PWG results indicate that permethrin induced a significant dose-dependent increase in the incidence of hepatocellular neoplasms in treated female mice ( p < .01) as well as a nonstatistically significant increase in the incidence of hepatocellular tumors in treated male mice. Given the continuum of the diagnoses of adenoma and carcinoma, and the difficulty in distinguishing some of the lesions, it is appropriate to consider only the combined incidences of hepatocellular tumors (adenoma and/or carcinoma) for biological significance and risk assessment.

scholarly journals Ovarian hormones mediate the prophylactic efficacy of (R,S)-ketamine and (2R,6R)-hydroxynorketamine in female mice

2019 ◽  
Author(s):  
Briana K. Chen ◽  
Christina T. LaGamma ◽  
Xiaoming Xu ◽  
Shi-Xian Deng ◽  
Rebecca A. Brachman ◽  
...  
Keyword(s):  
Learned Helplessness ◽  
Hormone Replacement ◽  
Ovarian Hormones ◽  
Contextual Fear Conditioning ◽  
Male Mice ◽  
Prophylactic Efficacy ◽  
Male And Female ◽  
Female Mice ◽  
Learned Fear ◽  
Necessary And Sufficient

ABSTRACTBACKGROUNDFemales are more likely than males to develop major depressive disorder (MDD) after exposure to stress. We previously reported that the administration of (R,S)-ketamine before stress can prevent stress-induced depressive-like behavior in male mice but have yet to assess efficacy in female mice or for other compounds, such as the metabolites of (R,S)-ketamine.METHODSWe administered (R,S)-ketamine or its metabolites (2R,6R)-hydroxynorketamine ((2R,6R)-HNK) and (2S,6S)-HNK at various doses 1 week before one of a number of stressors, including contextual fear conditioning (CFC), learned helplessness (LH), and chronic immobilization stress (CIS), in male and female 129S6/SvEv mice. To examine the interaction between ovarian hormones and stress resilience, female mice also underwent ovariectomy surgery (OVX) and a hormone replacement protocol prior to drug administration.RESULTS(R,S)-ketamine and (2S,6S)-HNK, but not (2R,6R)-HNK, attenuated learned fear in male mice. (R,S)-ketamine and (2R,6R)-HNK, but not (2S,6S)-HNK, significantly reduced stress-induced depressive-like behavior in male and female mice. (R,S)-ketamine and (2R,6R)-HNK) were prophylactically effective at a lower dose (10 mg/kg and 0.025 mg/kg, respectively) in female mice than in male mice (30 mg/kg and 0.075 mg/kg, respectively). Moreover, ovarian-derived hormones were necessary and sufficient for prophylaxis in female mice.CONCLUSIONSOur results suggest that prophylactics against stress-induced depressive-like behavior can be developed in a sex-specific manner and that ovarian hormones mediate prophylactic efficacy in females. To our knowledge, this is the first demonstration of the prophylactic efficacy of the metabolites of (R,S)-ketamine in male and female mice.

scholarly journals Adolescent intermittent ethanol exposure induces sex-dependent divergent changes in ethanol drinking and motor activity in adulthood in C57BL/6J mice

2020 ◽  
Author(s):  
Antoniette M. Maldonado-Devincci ◽  
Joseph G. Makdisi ◽  
Andrea M. Hill ◽  
Renee C. Waters ◽  
Nzia I. Hall ◽  
...  
Keyword(s):  
Open Field ◽  
Ethanol Consumption ◽  
Ethanol Exposure ◽  
Male Mice ◽  
Open Field Behavior ◽  
Male And Female ◽  
Female Mice ◽  
Binge Ethanol Exposure ◽  
Binge Ethanol

AbstractWith alcohol readily accessible to adolescents, its consumption leads to many adverse effects, including impaired learning, attention, and behavior. Adolescents report higher rates of binge drinking compared to adults. Adolescents are also more prone to substance use disorder during adulthood due to physiological changes during the adolescent developmental period. We used C57BL/6J male and female mice to investigate the long-lasting impact of binge ethanol exposure during adolescence on voluntary ethanol intake and open field behavior during later adolescence and in young adulthood. The present set of experiments were divided into four stages: (1) chronic intermittent vapor inhalation exposure, (2) abstinence, (3) voluntary ethanol intake, and (4) open field behavioral testing. During adolescence, male and female mice were exposed to air or ethanol using an intermittent vapor inhalation with repeated binge pattern ethanol exposure from postnatal day (PND) 28–42. Following this, mice underwent abstinence during late adolescence from PND 43–49 (Experiment 1) or PND 43–69 (Experiment 2). Beginning on PND 49–76 (Experiment 1) or PND 70–97 (Experiment 2), mice were assessed for intermittent voluntary ethanol consumption using a two-bottle drinking procedure over 28 days. Male mice that were exposed to ethanol during adolescence showed increased ethanol consumption during later adolescence (Experiment 1) and in emerging adulthood (Experiment 2), while the female mice showed decreased ethanol consumption. These data demonstrate a sexually divergent shift in ethanol consumption following binge ethanol exposure during adolescence and differences in open field behavior. These data highlight sex-dependent vulnerability to developing substance use disorders in adulthood.Significance StatementCurrently, it is vital to determine the sex-dependent impact of binge alcohol exposure during adolescence, given that until recently females have largely been ignored. Here we show that adolescent male mice that are exposed to binge ethanol during adolescence show long-term changes in behavior in adulthood. In contrast, female mice show a transient decrease in ethanol consumption in adulthood and decreased motor activity spent in the center zone of the open field test. Male mice appear to be more susceptible to the long-term changes in ethanol consumption following binge ethanol exposure during adolescence.

Certain aspects of the host-parasite relationship of Nematospiroides dubius (Baylis). I. Resistance of male and female mice to experimental infections

Parasitology ◽  
1961 ◽  
Vol 51 (1-2) ◽  
pp. 173-179 ◽  
Author(s):  
Colin Dobson
Keyword(s):  
Relative Length ◽  
Industrial Research ◽  
Male Mice ◽  
Male And Female ◽  
Female Mice ◽  
Host Parasite Relationship ◽  
Parasite Relationship ◽  
Nematospiroides Dubius ◽  
Host Parasite ◽  
Relationship Of

1. It has been shown that there is a difference between the resistance of male and female mice to infection with Nematospiroides dubius.2. More parasites were harboured, during both the larval and adult parasitic phases, by male mice.3. These worms were found to occupy a similar relative length of the intestine between the stomach and the caecum in male and female mice infected for either 5 or 10 days.4. The relative length of the intestine infected on the fifth day was significantly greater than that infected on the tenth day.This investigation was carried out during the tenure of a Research Studentship from the Department of Scientific and Industrial Research. I should like to thank Professor I. Chester Jones, in whose department the work was done, for the facilities provided and Dr E. T. B. Francis for his helpful and critical supervision.

Protective Effect of Calcium Dobesilate Administration Against Hepatorenal Damage Induced By CCL4 In Male Mice

2021 ◽  
Author(s):  
Elham Hakimizadeh ◽  
Ayat Kaeidi ◽  
Mohammadreza Rahmani ◽  
Mohammad Allahtavakoli ◽  
Jalal Hassanshahi
Keyword(s):  
Protective Effect ◽  
Antioxidant Properties ◽  
Group Versus ◽  
Histopathological Change ◽  
Renal Tissue ◽  
Protective Effects ◽  
Male Mice ◽  
Calcium Dobesilate ◽  
Liver And Kidney ◽  
Anti Inflammatory

Abstract Purpose: Calcium dobesilate (CaD) has antioxidant and anti-inflammatory properties. In this study, the protective effects of CaD against hepatorenal damage induced by CCL4 in male mice were evaluated. Methods: Thirty male mice randomly were divided into five groups: Control, CaD 100 mg/kg, CCL4, CCL4+CaD 50 mg/kg, and CCL4+CaD 100 mg/kg. Drugs were administered orally once a day for 4-weeks. The liver and kidney indices (serum creatinine, blood urine nitrogen, alanine aminotransferase and aspartate aminotransferase levels) were determined. Also, hepatic and renal tissue oxidant/antioxidant markers (glutathione peroxidase, malondialdehyde, total antioxidant capacity, and superoxide dismutase) were measured. Cleaved caspase-3, Bax, and Bcl-2 protein levels were measured by immunoblotting method. The liver and kidney histopathological changes were evaluated by H&E staining.Results: CCL4 induces significant oxidative stress in the kidney and liver that was concomitant with functional and histopathological abnormalities in these organs in the CCL4 group versus the control (P<0.05). CaD could significantly improve the histopathological change in the liver and kidney tissues of CCL4+CaD 100 mg/kg mice versus the CCL4 group (P<0.05). In addition, CaD attenuated apoptosis in the liver and kidney tissues (P<0.05).Conclusion: The protective effect of CaD may be related to its anti-inflammatory and antioxidant properties.

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