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.

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.

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 Nanocarriers, Progenitor Cells, Combinational Approaches, and New Insights on the Retinal Therapy

2021 ◽  
Vol 22 (4) ◽  
pp. 1776
Author(s):  
Elham Pishavar ◽  
Hongrong Luo ◽  
Johanna Bolander ◽  
Antony Atala ◽  
Seeram Ramakrishna
Keyword(s):  
Drug Delivery ◽  
Progenitor Cells ◽  
Transfection Efficiency ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Age Related Macular Degeneration ◽  
Therapeutic Approaches ◽  
Age Related ◽  
Nanofibrous Scaffolds ◽  
The Stability

Progenitor cells derived from the retinal pigment epithelium (RPECs) have shown promise as therapeutic approaches to degenerative retinal disorders including diabetic retinopathy, age-related macular degeneration and Stargardt disease. However, the degeneration of Bruch’s membrane (BM), the natural substrate for the RPE, has been identified as one of the major limitations for utilizing RPECs. This degeneration leads to decreased support, survival and integration of the transplanted RPECs. It has been proposed that the generation of organized structures of nanofibers, in an attempt to mimic the natural retinal extracellular matrix (ECM) and its unique characteristics, could be utilized to overcome these limitations. Furthermore, nanoparticles could be incorporated to provide a platform for improved drug delivery and sustained release of molecules over several months to years. In addition, the incorporation of tissue-specific genes and stem cells into the nanostructures increased the stability and enhanced transfection efficiency of gene/drug to the posterior segment of the eye. This review discusses available drug delivery systems and combination therapies together with challenges associated with each approach. As the last step, we discuss the application of nanofibrous scaffolds for the implantation of RPE progenitor cells with the aim to enhance cell adhesion and support a functionally polarized RPE monolayer.

scholarly journals Age influences susceptibility of brain capillary endothelial cells to La Crosse virus infection and cell death

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Rahul Basu ◽  
Vinod Nair ◽  
Clayton W. Winkler ◽  
Tyson A. Woods ◽  
Iain D. C. Fraser ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Cell Death ◽  
Virus Infection ◽  
La Crosse Virus ◽  
Brain Capillary ◽  
Adult Mice ◽  
Age Related ◽  
Capillary Endothelial Cells ◽  
The Brain

Abstract Background A key factor in the development of viral encephalitis is a virus crossing the blood-brain barrier (BBB). We have previously shown that age-related susceptibility of mice to the La Crosse virus (LACV), the leading cause of pediatric arbovirus encephalitis in the USA, was associated with the ability of the virus to cross the BBB. LACV infection in weanling mice (aged around 3 weeks) results in vascular leakage in the olfactory bulb/tract (OB/OT) region of the brain, which is not observed in adult mice aged > 6–8 weeks. Thus, we studied age-specific differences in the response of brain capillary endothelial cells (BCECs) to LACV infection. Methods To examine mechanisms of LACV-induced BBB breakdown and infection of the CNS, we analyzed BCECs directly isolated from weanling and adult mice as well as established a model where these cells were infected in vitro and cultured for a short period to determine susceptibility to virus infection and cell death. Additionally, we utilized correlative light electron microscopy (CLEM) to examine whether changes in cell morphology and function were also observed in BCECs in vivo. Results BCECs from weanling, but not adult mice, had detectable infection after several days in culture when taken ex vivo from infected mice suggesting that these cells could be infected in vitro. Further analysis of BCECs from uninfected mice, infected in vitro, showed that weanling BCECs were more susceptible to virus infection than adult BCECs, with higher levels of infected cells, released virus as well as cytopathic effects (CPE) and cell death. Although direct LACV infection is not detected in the weanling BCECs, CLEM analysis of brain tissue from weanling mice indicated that LACV infection induced significant cerebrovascular damage which allowed virus-sized particles to enter the brain parenchyma. Conclusions These findings indicate that BCECs isolated from adult and weanling mice have differential viral load, infectivity, and susceptibility to LACV. These age-related differences in susceptibility may strongly influence LACV-induced BBB leakage and neurovascular damage allowing virus invasion of the CNS and the development of neurological disease.

scholarly journals Distinct Changes in Gut Microbiota Are Associated with Estradiol-Mediated Protection from Diet-Induced Obesity in Female Mice

Metabolites ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 499
Author(s):  
Kalpana D. Acharya ◽  
Hye L. Noh ◽  
Madeline E. Graham ◽  
Sujin Suk ◽  
Randall H. Friedline ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Energy Homeostasis ◽  
Whole Body ◽  
Glucose Turnover ◽  
Female Mice ◽  
Adult Mice ◽  
Diet Induced Obesity ◽  
Metabolic Dysregulation ◽  
Regulation Of Metabolism ◽  
Junction Protein

A decrease in ovarian estrogens in postmenopausal women increases the risk of weight gain, cardiovascular disease, type 2 diabetes, and chronic inflammation. While it is known that gut microbiota regulates energy homeostasis, it is unclear if gut microbiota is associated with estradiol regulation of metabolism. In this study, we tested if estradiol-mediated protection from high-fat diet (HFD)-induced obesity and metabolic changes are associated with longitudinal alterations in gut microbiota in female mice. Ovariectomized adult mice with vehicle or estradiol (E2) implants were fed chow for two weeks and HFD for four weeks. As reported previously, E2 increased energy expenditure, physical activity, insulin sensitivity, and whole-body glucose turnover. Interestingly, E2 decreased the tight junction protein occludin, suggesting E2 affects gut epithelial integrity. Moreover, E2 increased Akkermansia and decreased Erysipleotrichaceae and Streptococcaceae. Furthermore, Coprobacillus and Lactococcus were positively correlated, while Akkermansia was negatively correlated, with body weight and fat mass. These results suggest that changes in gut epithelial barrier and specific gut microbiota contribute to E2-mediated protection against diet-induced obesity and metabolic dysregulation. These findings provide support for the gut microbiota as a therapeutic target for treating estrogen-dependent metabolic disorders in women.

scholarly journals Preconceptional Resveratrol Supplementation Partially Counteracts Age-Related Reproductive Complications in C57BL/6J Female Mice

Molecules ◽  
2021 ◽  
Vol 26 (7) ◽  
pp. 1934
Author(s):  
Marta Ziętek ◽  
Katarzyna Barłowska ◽  
Barbara Wijas ◽  
Ewa Szablisty ◽  
Atanas G. Atanasov ◽  
...  
Keyword(s):  
Drinking Water ◽  
Animal Models ◽  
Mating Success ◽  
Pregnancy Outcomes ◽  
Pregnancy Complications ◽  
Polyphenolic Compound ◽  
Female Mice ◽  
Age Related ◽  
Increased Risk ◽  
Anti Oxidant

Aging is associated with a drastic decline in fertility/fecundity and with an increased risk of pregnancy complications. Resveratrol (RES), a natural polyphenolic compound, has shown anti-oxidant and anti-inflammatory activities in both human and animal models, thus representing a potential therapeutic and prophylactic anti-aging supplement. Here, we investigated whether preconceptional resveratrol supplementation improved reproductive outcomes in mid-aged (8-month-old) and old (12-month-old) C57BL/6J female mice. Female siblings were cohoused and assigned to either RES or vehicle supplementation to drinking water for 10 consecutive weeks. Subsequently, females were mated with non-supplemented males and their pregnancy outcomes were monitored. RES improved mating success in old, but not in mid-aged females, and prevented the occurrence of delivery complications in the latter. These results indicate that preconceptional RES supplementation could partially improve age-related reproductive complications, but it was not sufficient to restore fecundity in female mice at a very advanced age.

EFFECTS OF GENERAL ANAESTHESIA AND SEVERITY OF SURGICAL STRESS ON SERUM LH AND TESTOSTERONE IN MALES

1975 ◽  
Vol 78 (2) ◽  
pp. 258-269 ◽  
Author(s):  
A. Nakashima ◽  
K. Koshiyama ◽  
T. Uozumi ◽  
Y. Monden ◽  
Y. Hamanaka ◽  
...  
Keyword(s):  
General Anaesthesia ◽  
Surgical Stress ◽  
Fiberoptic Bronchoscopy ◽  
Serum Testosterone ◽  
Major Surgery ◽  
Succinylcholine Chloride ◽  
Serum Luteinizing Hormone ◽  
Serum Lh ◽  
Rate Of Increase ◽  
Male Patients

ABSTRACT Significantly decreased levels of serum testosterone from the pre-anaesthesia level were found during and up to 7 days following major surgery under general anaesthesia (nitrous oxide, oxygen and halothane following induction with thiopental and succinylcholine chloride) in 18 male patients. On the other hand, in the same patients, the serum luteinizing hormone (LH) increased significantly from the pre-anaesthesia level 30 min and 1 h after the beginning of anaesthesia. A slight increase in LH level was also noted on the 7th post-operative day. The determinations of serum testosterone and LH in fiberoptic bronchoscopy under the same general anaesthesia as that used in surgery or local anaesthesia in 26 male patients, revealed that the change in the serum LH during and following surgery seemed to be mainly induced by the general anaesthesia and that the rate of decrease in the serum testosterone may be related to the severity of surgical stress including the anaesthesia. The rate of increase in serum testosterone following the injection of gonadotrophin in 20 males on the 6th post-operative day was similar to that in 10 pre-operative males. The effects of pulmonary lobectomy on serum testosterone and urinary steroids were also studied in 6 males under adrenal suppression with dexamethasone. On the 6th post-operative day, the urinary aetiocholanolone plus androsterone and serum testosterone were found to be half the level of those on the pre-operative day, while the urinary 5β-pregnane-3α,17α,20α-triol remained unchanged. These observations in human are not inconsistent with the report of Tcholakian & Eik-Nes (1971) in dogs namely that a shift in androgen biosynthetic pathway is present in the testis under surgical stress.

scholarly journals Age-Related Association of Calcitonin with Parameters of Anthropometry, Bone and Calcium Metabolism during Childhood

2020 ◽  
pp. 1-10
Author(s):  
Juliane Sonntag ◽  
Mandy Vogel ◽  
Mandy Geserick ◽  
Felix Eckelt ◽  
Antje Körner ◽  
...  
Keyword(s):  
Bone Formation ◽  
Bone Growth ◽  
Venous Blood ◽  
Physiological Role ◽  
Blood Levels ◽  
Childhood And Adolescence ◽  
Procollagen Type ◽  
Child Study ◽  
Age Related ◽  
High Bone

<b><i>Introduction:</i></b> The thyroid parafollicular hormone calcitonin (CT) shows particularly high blood levels in early childhood, a period of high bone turnover, which decrease with increasing age. Data about the physiological role of CT during infancy, childhood, and adolescence are contradictory or lacking. <b><i>Objective:</i></b> We hypothesize that CT demonstrates age-related correlations with parameters of bone growth and turnover as well as with parameters of calcium homeostasis. <b><i>Methods:</i></b> 5,410 measurements of anthropometric data and venous blood samples were collected from 2,636 participants of the LIFE Child study, aged 2 months–18 years. Univariate correlations and multiple regression analysis were performed between serum CT and anthropometric indicators (height standard deviation scores [SDS] and BMI-SDS), markers of calcium (Ca) homeostasis (Ca, parathyroid hormone, 25-OH vitamin D, and phosphate [P]), bone formation (procollagen type 1 N-terminal propeptide [P1NP], osteocalcin), and bone resorption (β-CrossLaps). <b><i>Results:</i></b> CT was significantly associated with Ca (β = 0.26, <i>p</i> &#x3c; 0.05) and P1NP/100 (β = 0.005, <i>p</i> &#x3c; 0.05) in children aged 2 months–1.1 years. These relations were independent of age and sex and could not be confirmed in children aged 1.1–8 years. Independent of age, sex, puberty, P, and height SDS CT showed a significant positive relation to Ca (β = 0.26; <i>p</i> &#x3c; 0.001) in children aged 8–18 years. <b><i>Conclusions:</i></b> Our findings suggest a unique association between CT and Ca in periods of rapid bone growth and point to a possible involvement of CT in promoting bone formation during the first year of life.

Abstract 3426: Myostatin Deletion Preserves Cardiac Function in Senescent Mice

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Michael R Morissette ◽  
Janelle C Stricker ◽  
Anthony Rosenzweig
Keyword(s):  
Cardiac Function ◽  
Rhode Island ◽  
Cardiac Fibrosis ◽  
Physiological Role ◽  
Heart Association ◽  
Negative Regulator ◽  
Heart Weight ◽  
Cardiomyocyte Hypertrophy ◽  
Mrna Levels ◽  
Age Related

Myostatin (MSTN) is a well-known negative regulator of skeletal muscle mass, and MSTN inhibition is being considered as therapy for multiple conditions associated with muscle wasting, including sarcopenia of aging. We have previously shown that MSTN inhibits phenylephrine-induced cardiomyocyte hypertrophy, however whether MSTN has a physiological role in regulating cardiac hypertrophy or function at baseline or with aging remains unclear. To determine if MSTN is dynamically regulated with aging, we performed QRT-PCR on hearts from male wild-type (WT) senescent mice (24 months old (mos)) and rats (32 mos). MSTN mRNA levels were increased in old versus young (4 mos) hearts (2.5- and 4-fold respectively, p<0.05). To study the functional significance of MSTN in aging, we maintained germline MSTN-knockout mice (MSTN −/− ) and their WT littermates for 24 –27 months. We found no difference in heart weight of aged male MSTN −/− compared to WT mice (162.5±17.0 (n=4) vs 153.2±4.2 (n=4) mg, p=0.51), which would argue against an inhibitory role for MSTN in age-related increases in cardiac mass. We also performed echocardiography on unanesthetized senescent MSTN −/− and WT mice. MSTN −/− mice had better fractional shortening (58.1±2.0 (n=7) vs 49.4±1.2 (n=8) %, p=0.002) and smaller LV end-diastolic diameter (3.41±0.19 vs 2.71±0.14 mm, p=0.012) compared to WT. The decreased cardiac function seen in aged WT mice was associated with increased cardiac fibrosis on Masson-Trichrome stained sections. Western blot analysis also demonstrated a 3.3-fold increase in phospholamban phosphorylation in MSTN −/− hearts (p<0.05), compared to WT, while no differences in SERCA2a or calsequestrin protein levels were seen. We conclude that MSTN increases in the heart with aging, and that genetic deletion of MSTN results in improved cardiac function without a difference in heart mass in senescent mice. Decreased cardiac fibrosis and increased inhibition (phosphorylation) of phospholamban likely contribute to the better cardiac function seen in senescent MSTN −/− mice. These results suggest that inhibiting MSTN for sarcopenia in the elderly may also benefit cardiac function and could represent a novel therapeutic approach for ameliorating cardiac dysfunction and/or fibrosis. This research has received full or partial funding support from the American Heart Association, AHA Founders Affiliate (Connecticut, Maine, Massachusetts, New Hampshire, New Jersey, New York, Rhode Island, Vermont).

Sign in / Sign up

Export Citation Format

Share Document