scholarly journals Membrane progesterone receptor-β, but not -α, in dorsal brain stem establishes sex-specific chemoreflex responses and reduces apnea frequency in adult mice

2016 ◽  
Vol 121 (3) ◽  
pp. 781-791 ◽  
Author(s):  
Ryma Boukari ◽  
Orlane Rossignol ◽  
Cécile Baldy ◽  
François Marcouiller ◽  
Aida Bairam ◽  
...  
Keyword(s):  
Brain Stem ◽  
Progesterone Receptors ◽  
Respiratory Control ◽  
Staining Intensity ◽  
Whole Body ◽  
Male And Female ◽  
Female Mice ◽  
Adult Mice ◽  
Specific Effects ◽  
Membrane Progesterone Receptor

We tested the hypothesis that membrane progesterone receptors (mPR) contribute to respiratory control in adult male and female mice. Mice were implanted with osmotic minipumps for continuous infusion of small interfering RNA (siRNA) directed against mPRα, mPRβ, or a control solution in the fourth ventricle (to target brain stem respiratory areas) for 14 days. We then performed respiratory and metabolic recordings by whole body plethysmography at rest and in response to hypoxia (12% O2) or hypercapnia (5% CO2, 5 min each). For each treatment, we have verified with immunohistochemistry that the staining intensity of mPRα or mPRβ in the brain stem is decreased. At rest, the siRNA against mPRα and mPRβ increased respiratory frequency in males only. The siRNA against mPRβ almost tripled the frequency of apneas in male and in female mice, while the siRNA against mPRα had no effect. Regarding respiratory chemoreflex, the siRNA against mPRβ suppressed the response to hypoxia in male and female mice and reduced by ∼50% the response to hypercapnia, while the siRNA against mPRα had more limited effects. Interestingly, control females had higher ventilatory response to hypoxia and hypercapnia than males, and these sex-specific effects were suppressed by the siRNA against mPRβ, whereas they were still present after treatment with the siRNA against mPRα. We conclude that mPRβ reduces apnea frequency in male and female mice and establishes sex-specific ventilatory chemoreflex.

Endogenous brain erythropoietin is a potent sex-specific respiratory stimulant in adult and newborn mice

2015 ◽  
Vol 118 (11) ◽  
pp. 1386-1395 ◽  
Author(s):  
Orlane Ballot ◽  
Vincent Joseph ◽  
Jorge Soliz
Keyword(s):  
Ventilatory Response ◽  
Minute Ventilation ◽  
Whole Body ◽  
Newborn Mice ◽  
Male And Female ◽  
Female Mice ◽  
Specific Effects ◽  
Respiratory Stimulant ◽  
Males And Females ◽  
Whole Body Plethysmography

We tested the hypothesis that endogenous brain Epo is a respiratory stimulant. Adult (3 mo) and newborn (10 days) male and female mice received an intracisternal (cisterna magna) injection of soluble Epo receptor (sEpoR; competes with EpoR to bind Epo; 50 μg/ml) or vehicle (0.1% BSA in PBS). Twenty-four hours after injection, we used whole body plethysmography to record minute ventilation (V̇e) tidal volume (VT), respiratory frequency ( fR), O2 consumption (V̇o2), and CO2 production (V̇co2) under normoxia and progressive exposure to hypoxia (12-10-6% O2; 10 min each). In adult male and female mice sEpoR decreased normoxic V̇e (−25%), due to a decrease of VT in males and fR in females. Moreover, sEpoR injection decreased the ventilatory response to 12% O2, assessed as V̇e/V̇o2 or V̇e/V̇co2, in male but not in female mice. In newborn male and female mice sEpoR decreased V̇e (−37% in males, −59% in females) and VT (−38% in males, −47% in females) in normoxia and fR in females. During hypoxia, sEpoR decreased V̇e/V̇o2 and V̇e/V̇co2 in mice of both sexes. Upon extreme hypoxia (6% O2), the newborn mice treated with sEpoR showed respiratory depression, signs of asphyxia (gasping) and a high mortality rate in males and females. We concluded that endogenous brain Epo is a potent respiratory stimulant under normoxia and hypoxia in adult and newborn mice. Because sex-specific effects are different in newborn male and female, sex steroids secreted at different ages mice appear to modulate the effects of Epo on respiratory regulation in normoxia and in response to hypoxia.

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.

Rate of loss of radioiron from mouse and man

1960 ◽  
Vol 198 (4) ◽  
pp. 784-786 ◽  
Author(s):  
John D. Bonnet ◽  
Alan L. Orvis ◽  
Albert B. Hagedorn ◽  
Charles A. Owen
Keyword(s):  
Life Span ◽  
Half Life ◽  
Whole Body ◽  
Entire Body ◽  
Rapid Loss ◽  
Male And Female ◽  
Female Mice ◽  
Steady Rate ◽  
Normal Man ◽  
The Difference

Forty-two male and female mice, 8 weeks old, were given radioiron (Fe59) in doses of 0.006–0.1 µc, containing 0.013–0.17 µg of iron, by intraperitoneal or intravenous routes. Assays of the radioactivity of the whole body revealed an initial rapid loss of Fe59 (15–20%) lasting about 6 days. Thereafter the Fe59 left the mice at a steady rate of 0.39%/day (half-life 180 days). One 34-year-old normal man was given 10.6 µc of Fe59, containing 8.2 µg of iron, intravenously. Based on counts from the entire body, the biologic rate of loss of the Fe59 was about 0.14%/day (half-life 500 days), and there was little or no initial loss such as occurred in the mouse. The Fe59 in the circulating erythrocytes was essentially unchanged for the first 3 months. It then fell to a new level of about 90% of the previous one; the mid-point of the fall was about 120 days after the administration of the radioiron. The difference in the rates of loss of radioiron from mice and man seems to be related primarily to the life span of the circulating red cells.

scholarly journals CTRP3 deficiency reduces liver size and alters IL-6 and TGFβ levels in obese mice

2016 ◽  
Vol 310 (5) ◽  
pp. E332-E345 ◽  
Author(s):  
Risa M. Wolf ◽  
Xia Lei ◽  
Zhi-Chun Yang ◽  
Maeva Nyandjo ◽  
Stefanie Y. Tan ◽  
...  
Keyword(s):  
Serum Levels ◽  
Whole Body ◽  
Activity Levels ◽  
Loss Of Function ◽  
Physiological Control ◽  
Liver Size ◽  
Male And Female ◽  
Female Mice ◽  
Obesity And Diabetes ◽  
Similar Weight

C1q/TNF-related protein 3 (CTRP3) is a secreted metabolic regulator whose circulating levels are reduced in human and rodent models of obesity and diabetes. Previously, we showed that CTRP3 infusion lowers blood glucose by suppressing gluconeogenesis and that transgenic overexpression of CTRP3 protects mice against diet-induced hepatic steatosis. Here, we used a genetic loss-of-function mouse model to further address whether CTRP3 is indeed required for metabolic homeostasis under normal and obese states. Both male and female mice lacking CTRP3 had similar weight gain when fed a control low-fat (LFD) or high-fat diet (HFD). Regardless of diet, no differences were observed in adiposity, food intake, metabolic rate, energy expenditure, or physical activity levels between wild-type (WT) and Ctrp3-knockout (KO) animals of either sex. Contrary to expectations, loss of CTRP3 in LFD- or HFD-fed male and female mice also had minimal or no impact on whole body glucose metabolism, insulin sensitivity, and fasting-induced hepatic gluconeogenesis. Unexpectedly, the liver sizes of HFD-fed Ctrp3-KO male mice were markedly reduced despite a modest increase in triglyceride content. Furthermore, liver expression of fat oxidation genes was upregulated in the Ctrp3-KO mice. Whereas the liver and adipose expression of profibrotic TGFβ1, as well as its serum levels, was suppressed in HFD-fed KO mice, circulating proinflammatory IL-6 levels were markedly increased; these changes, however, were insufficient to affect systemic metabolic outcome. We conclude that, although it is dispensable for physiological control of energy balance, CTRP3 plays a previously unsuspected role in modulating liver size and circulating cytokine levels in response to obesity.

scholarly journals Phox2b mutation mediated by Atoh1 expression impaired respiratory rhythm and ventilatory responses to hypoxia and hypercapnia

2021 ◽  
Author(s):  
Caroline B Ferreira ◽  
Talita M Silva ◽  
Phelipe E Silva ◽  
Catherine Czeisler ◽  
Jose J Otero ◽  
...  
Keyword(s):  
Respiratory Rhythm ◽  
Adult Life ◽  
Respiratory Control ◽  
Lineage Tracing ◽  
Whole Body ◽  
Transgenic Mouse Line ◽  
Ventilatory Responses ◽  
Retrotrapezoid Nucleus ◽  
Adult Mice ◽  
Hypoventilation Syndrome

Retrotrapezoid nucleus (RTN) neurons are involved in central chemoreception and respiratory control. Lineage tracing studies demonstrate RTN neurons to be derived from Phox2b and Atoh1 expressing progenitor cells in rhombere 4. Phox2b exon 3 mutations cause congenital central hypoventilation syndrome (CCHS), producing an impaired respiratory response to hypercapnia and hypoxia. Our goal was to investigate the extent to which a conditional mutation of Phox2b within Atoh1-derived cells might affect a) respiratory rhythm; b) ventilatory responses to hypercapnia and hypoxia and c) number of RTN-chemosensitive neurons. Here, we used a transgenic mouse line carrying a conditional Phox2bΔ8 mutation activated by cre-recombinase. We crossed them with Atoh1Cre mice. Ventilation was measured by whole body plethysmograph during neonate and adult life. In room air, experimental and control groups showed similar basal ventilation; however, Atoh1Cre/Phox2bΔ8 increased breath irregularity. The hypercapnia and hypoxia ventilatory responses were impaired in neonates. In contrast, adult mice recovered ventilatory response to hypercapnia, but not to hypoxia. Anatomically, we observed a reduction of the Phox2b+/TH- expressing neurons within the RTN region. Our data indicates that conditionally expression of Phox2b mutation by Atoh1 affect development of the RTN neurons and are essential for the activation of breathing under hypoxic and hypercapnia condition, providing new evidence for mechanisms related to CCHS neuropathology

scholarly journals Cerebral Erythropoietin Prevents Sex-Dependent Disruption of Respiratory Control Induced by Early Life Stress

2021 ◽  
Vol 12 ◽  
Author(s):  
Elizabeth Elliot-Portal ◽  
Christian Arias-Reyes ◽  
Sofien Laouafa ◽  
Rose Tam ◽  
Richard Kinkead ◽  
...  
Keyword(s):  
Life Stress ◽  
Early Life ◽  
Maternal Separation ◽  
Stress Hormones ◽  
Respiratory Control ◽  
Early Life Stress ◽  
Whole Body ◽  
Wild Type ◽  
Adult Mice ◽  
Respiratory Disturbance

Injuries that occur early in life are often at the root of adult illness. Neonatal maternal separation (NMS) is a form of early life stress that has persistent and sex-specific effects on the development of neural networks, including those that regulate breathing. The release of stress hormones during a critical period of development contributes to the deleterious consequences of NMS, but the role of increased corticosterone (CORT) in NMS-induced respiratory disturbance is unknown. Because erythropoietin (EPO) is a potent neuroprotectant that prevents conditions associated with hyperactivation of the stress neuroaxis in a sex-specific manner, we hypothesized that EPO reduces the sex-specific alteration of respiratory regulation induced by NMS in adult mice. Animals were either raised under standard conditions (controls) or exposed to NMS 3 h/day from postnatal days 3–12. We tested the efficacy of EPO in preventing the effects of NMS by comparing wild-type mice with transgenic mice that overexpress EPO only in the brain (Tg21). In 7-days-old pups, NMS augmented CORT levels ~2.5-fold by comparison with controls but only in males; this response was reduced in Tg21 mice. Respiratory function was assessed using whole-body plethysmography. Apneas were detected during sleep; the responsiveness to stimuli was measured by exposing mice to hypoxia (10% O2; 15 min) and hypercapnia (5% CO2; 10 min). In wild-type, NMS increased the number of apneas and the hypercapnic ventilatory response (HcVR) only in males; with no effect on Tg21. In wild-type males, the incidence of apneas was positively correlated with HcVR and inversely related to the tachypneic response to hypoxia. We conclude that neural EPO reduces early life stress-induced respiratory disturbances observed in males.

Lead in the Water Supply Alters Swimming-Maze Behavior in Adult Mice

1982 ◽  
Vol 55 (2) ◽  
pp. 507-512 ◽  
Author(s):  
K. Mc Lean ◽  
G. H. Parker ◽  
M. A. Persinger
Keyword(s):  
Drinking Water ◽  
Water Supply ◽  
Tap Water ◽  
Test Block ◽  
Food Regime ◽  
Male And Female ◽  
Female Mice ◽  
Adult Mice ◽  
Body Weights ◽  
Ad Libitum

After about two weeks of exposure to either 20 ppm or approximately 2000 ppm of lead in the drinking water or tap water only and under an ad libitum or restricted food regime, albino male and female mice ( N = 48) were tested for three consecutive days (3 blocks of 3 trials per day) in a swimming maze. Body weights were not altered by lead treatments significantly. The mice treated with the lead displayed longer escape latencies and more errors than the controls on tap water. Statistically significant interactions of lead treatment by test day by test block were also apparent.

Abstract 628: Efficient Excretion of Xenosterols in the Absence of Abcg5/Abcg8

2016 ◽  
Vol 36 (suppl_1) ◽  
Author(s):  
Shailendra B Patel
Keyword(s):  
Body Weight ◽  
Plant Sterols ◽  
Whole Body ◽  
Pathological Changes ◽  
Rapid Loss ◽  
Male And Female ◽  
Female Mice ◽  
Kinetics Of ◽  
Sterol Trafficking

Hypothesis: Xenosterol excretion by the mammalian body is wholly dependent on Abcg5/Abcg8 function. Methods: To test our hypothesis, we loaded Abcg8-/- mice with dietary plant sterols until they manifested biochemical (elevated plant sterols) and pathological changes (poor body weight, macrothrombocytopenia). All dietary xenosterols were eliminated from the diet and kinetics of xenosterol loss monitored over the ensuing 16 days, monitoring plasma, bile, and stool losses, as well as whole body sterol determinations. Results: After loading Abcg8-/- mice with plant sterols, plasma sitosterol levels in both male and female mice averaged 80mg/dL. Surprisingly, there was rapid loss of xenosterols from blood as well as tissues (liver, whole body), with losses of xenosterols detected in bile and feces. By day 16, stool xenosterols were almost undetectable and reflected the dramatic loss of whole body xenosterols. Conclusions: Our data refute our hypothesis. Although loss of sterolin function leads to severe xenosterolemia in both humans and mice, at least in mice, there appears to be a pathway(s) for elimination via the biliary/intestinal route. Characterization of the transporters involved may shed further light on sterol trafficking.

Effects of Neonatal Caffeine Administration on Vessel Reactivity in Adult Mice

2020 ◽  
Author(s):  
Ajay Pratap Singh ◽  
Praveen Chandrasekharan ◽  
Sylvia Gugino ◽  
Sara Berkelhamer ◽  
Huamei Wang ◽  
...  
Keyword(s):  
Chronic Stress ◽  
Systemic Blood Pressure ◽  
Systemic Hypertension ◽  
Male Mice ◽  
Treated Male ◽  
Female Mice ◽  
Adult Mice ◽  
Specific Effects ◽  
Lower Body Weight ◽  
The Impact

Abstract Objective The effects of neonatal caffeine therapy in adults born preterm are uncertain. We studied the impact of neonatal caffeine on systemic blood pressure, vessel reactivity, and response to stress in adult mice. Study Design Mice pups were randomized to caffeine (20 mg/kg/d) or saline by intraperitoneal injection for 10 days after birth. We performed tail-cuff BP (8/12 weeks), urinary 8-hydroxydeoxyguanosine and fecal corticosterone (14 weeks), and vessel reactivity in aortic rings (16 weeks) in adult mice. Results No differences were noted in systolic, diastolic, and mean blood pressures between the two groups at 8 and 12 weeks of age. However, norepinephrine-induced vasoconstriction was substantially higher in aortic rings in CAF-treated male mice. More significant vasodilator responses to nitric oxide donors in aortic rings in female mice may suggest gender-specific effects of caffeine. Female mice exposed to caffeine had significantly lower body weight over-time. Caffeine-treated male mice had substantially higher fecal corticosterone and urinary 8-hydroxydeoxyguanosine at 14 weeks, suggestive of chronic stress. Conclusion We conclude sex-specific vulnerability to the heightened vascular tone of the aorta in male mice following neonatal caffeine therapy. Altered vessel reactivity and chronic stress in the presence of other risk factors may predispose to the development of systemic hypertension in adults born preterm.

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