Combined Effects of Exercise and Phytoanabolic Extracts in Castrated Male and Female Mice.
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ABSTRACT:
SUBMITTER: Martins JP
PROVIDER: S-EPMC8066446 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Aerobic exercise is a promising intervention to attenuate frailty, but preclinical studies have used only male animals. We investigated the impact of voluntary aerobic exercise on frailty, biological age (FRailty Inferred Geriatric Health Timeline [FRIGHT] clock), predicted life expectancy (Analysis of FRAIlty and Death [AFRAID] clock), and mortality in both sexes and determined whether exercise was associated with changes in inflammation. Older (21-23 months) male (n = 12) and female (n = 22) C57Bl/6 mice matched for baseline frailty scores were randomized into exercise (running wheel) and sedentary (no wheel) groups. Frailty index scores were measured biweekly (13 weeks), and 23 serum cytokines were measured at midpoint and end point. Exercise levels varied between mice but not between the sexes. Exercise had no effect on mortality, but it attenuated the development of frailty in both sexes (female = 0.32 ± 0.04 vs 0.21 ± 0.01; p = .005; male = 0.30 ± 0.02 vs 0.22 ± 0.02; p = .042) and reduced frailty in older females after 10 weeks. FRIGHT scores were unaffected by exercise but increased with time in sedentary males indicating increased biological age. Exercise prevented the age-associated decline in AFRAID scores in older females such that exercised females had a longer life expectancy. We investigated whether aerobic exercise was associated with changes in systemic inflammation. Cytokine levels were not affected by exercise in males, but levels of pro-inflammatory cytokines were positively correlated with the frequency of exercise in females. Despite increases in systemic inflammation, exercise reduced frailty and increased life span in older females. Thus, voluntary aerobic exercise, even late in life, has beneficial effects on health in both sexes but may be especially helpful in older females.
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Project description:Maternal obesity (MO) impairs maternal and offspring health. Mechanisms and interventions to prevent adverse maternal and offspring outcomes need to be determined. Human studies are confounded by socio-economic status providing the rationale for controlled animal data on effects of maternal exercise (MEx) intervention on maternal (F0) and offspring (F1) outcomes in MO.MO produces metabolic and endocrine dysfunction, increases maternal and offspring glucocorticoid exposure, oxidative stress and adverse offspring outcomes by postnatal day (PND) 36. MEx in part prevents these outcomes.F0 female rats ate either control or obesogenic diet from weaning through lactation. Half of each group wheel ran (from day 90 of life through pregnancy beginning day 120) providing four groups (n=8/group)--(i) controls, (ii) obese, (iii) exercised controls and (iv) exercised obese. After weaning, PND 21, F1 offspring ate a control diet. Metabolic parameters of F0 prepregnancy and end of lactation and F1 offspring at PND 36 were analyzed.Exercise did not change maternal weight. Before breeding, MO elevated F0 glucose, insulin, triglycerides, cholesterol, leptin, fat and oxidative stress. Exercise completely prevented the triglyceride rise and partially increases glucose, insulin, cholesterol and oxidative stress. MO decreased fertility, recovered by exercise. At the end of lactation, exercise returned all metabolic variables except leptin to control levels. Exercise partially prevented MO elevated corticosterone. F1 offspring weights were similar at birth. At PND 36, MO increased F1 male but not female offspring leptin, triglycerides and fat mass. In controls, exercise reduced male and female offspring glucose, prevented the offspring leptin increase and partially the triglyceride rise.MEx before and during pregnancy has beneficial effects on the maternal and offspring metabolism and endocrine function occurring with no weight change in mothers and offspring indicating the importance of body composition rather than weight in evaluations of metabolic status.
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Project description:Major depressive disorder and related illnesses are globally prevalent, with a significant risk for suicidality if untreated. Antidepressant drugs that are currently prescribed do not benefit 30% of treated individuals. Furthermore, there is a delay of 3 or more weeks before a reduction in symptoms. Results from preclinical studies have indicated an important role for trophic factors in regulating behavior. Erythropoietin (Epo), which is widely prescribed for anemia, has been shown to produce robust neurotrophic actions in the CNS. Although Epo's antidepressant activity has been successfully demonstrated in multiple clinical trials, the inherent ability to elevate RBC counts and other hematological parameters preclude its development as a mainstream CNS drug. A chemically engineered derivative, carbamoylated Epo (Cepo) has no hematological activity, but retains the neurotrophic actions of Epo. Cepo is therefore an attractive candidate to be tested as an antidepressant.ObjectiveTo evaluate the antidepressant properties of Cepo in established antidepressant-responsive rodent behavioral assays.MethodsAdult male and female BALB/c mice were used for this study. Cepo (30 ?grams/ kg BWT) or vehicle (PBS) was administered intraperitoneally for 4?days before the test of novelty induced hypophagia and subsequently at five hours before testing in forced swim test (FST), tail suspension test (TST) and open field test (OFT). To obtain mechanistic insight we examined the phosphorylation of the transcription factor cAMP response element binding protein (CREB).ResultsAdministration of Cepo at 30 ?grams/ kg BWT, for 4?days produced significant reduction in latency to consume a palatable drink in a novel environment in male and female mice. Male BALB/c mice had a significant reduction in immobility in both tail suspension and forced swim tests, and female mice exhibited lower immobility in the forced swim test.
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Project description:The optimized use of dietary nutrients and the accurate knowledge of the growth dynamics of body components is important for efficient pig production. This study aimed at evaluating the growth of carcass components and organs of Swiss Large White pigs from birth to 140 kg BW depending on the CP and amino acid (AA) supply. A total of 66 entire males (EM), 58 castrates (CA) and 66 female (FE) pigs were used. From 20 kg BW onwards, they had either ad libitum access to a control (C) or a diet (LP) with 20% lower CP, lysine, methionine + cystine, threonine and tryptophan content compared to C. The weight of organs, primal cuts and external fat were recorded in eight EM and eight FE; at 10 kg BW, on two EM, CA and FE each, and at 20 kg BW, on eight pigs from each sex. From 40 to 140 kg BW at 20 kg intervals, measurements were recorded on four pigs per sex and dietary treatment. The weight of each component was related to empty body (EB) using allometric regressions. Kidneys were heavier (P<0.05) in C- than LP-pigs and in EM than CA and FE. Above 21 kg EB weight, growth rate of LP-FE overpassed (P<0.05) the one of C-pigs. Consequently, LP-FE had heavier (P<0.05) lean cuts than C-pigs in the finisher period. However, LP-CA and LP-EM displayed lower (P<0.05) weights and growth rates of the lean cuts than C-CA and C-EM. Shoulder and loin weights and growth rates were reduced (P<0.05) in LP-pigs when compared to C-pigs. Growth rates of the ham were greater (P<0.05) in LP-FE than C-FE, whereas in LP-EM and LP-CA they were lower (P<0.05) than their C-counterparts. Total amounts of subcutaneous fat, backfat, ham fat and shoulder fat were lower (P<0.05) in C- than LP-pigs. The total amount of subcutaneous fat, backfat and shoulder fat of C-CA was, regardless of diet, greater (P<0.05) than of C-FE. In the LP group, this difference was even more pronounced. The amount of deposited ham fat was greater (P<0.05) in LP-CA than LP-FE, but not in C-CA v. C-FE. Differences in kidney weights suggested a greater nitrogen clearance required in C-pigs. Overall, dietary restriction and sex did not affect all body parts to the same extent. This study further suggests the possibility to reduce the CP and AA supply in FE without compromising the yield of primal lean cuts or increasing the amount of subcutaneous fat.
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Project description:In drug self-administration procedures, extended-access test sessions allow researchers to model maladaptive patterns of excessive and escalating drug intake that are characteristic of human substance-abusing populations.The purpose of the present study was to examine the ability of aerobic exercise to decrease excessive and escalating patterns of drug intake in male and female rats responding under extended-access conditions.Male and female Long-Evans rats were obtained at weaning and divided into sedentary (no running wheel) and exercising (running wheel) groups immediately upon arrival. After 6 weeks, rats were surgically implanted with intravenous catheters and allowed to self-administer cocaine under positive reinforcement contingencies. In experiment 1, cocaine self-administration was examined during 23-h test sessions that occurred every 4 days. In experiment 2, the escalation of cocaine intake was examined during daily 6-h test sessions over 14 consecutive days.In experiment 1, sedentary rats self-administered significantly more cocaine than exercising rats during uninterrupted 23-h test sessions, and this effect was apparent in both males and females. In experiment 2, sedentary rats escalated their cocaine intake to a significantly greater degree than exercising rats over the 14 days of testing. Although females escalated their cocaine intake to a greater extent than males, exercise effectively attenuated the escalation of cocaine intake in both sexes.These data indicate that aerobic exercise decreases maladaptive patterns of excessive and escalating cocaine intake under extended-access conditions.
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Project description:Long-term consumption of a diet with excessive fat and sucrose (Western diet, WD) leads to an elevated risk of obesity and metabolic syndrome in both males and females. However, there are sexual dimorphisms in metabolism which are apparent when considering the prevalence of complications of metabolic syndrome, such as non-alcoholic fatty liver disease. This study aimed to elucidate the impact of a WD on the metabolome and the gut microbiota of male and female mice at 5, 10, and 15 months to capture the dynamic and comprehensive changes brought about by diet at different stages of life. Here we show that there are important considerations of age and sex that should be considered when assessing the impact of diet on the gut microbiome and health.
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Project description:BackgroundAcute and chronic alcohol use can cause skeletal muscle myopathy in concert with impairments in skeletal muscle strength, function and fatigue resistance. However, the fundamental contractile deficits induced in the presence of alcohol versus those observed in the recovery period following the clearance of alcohol have not yet been characterized nor is it known whether sex influences these outcomes.MethodsMale and female mice received an intraperitoneal injection of either saline (Control) or ethanol (EtOH; 5g/kg body weight). Muscle force, fatigue, fatigue recovery and twitch characteristics of the posterior crural muscle complex were measured in situ 1 hour and 24 hours post alcohol.ResultsIn the presence of alcohol (1-hour post treatment) absolute and normalized force generated at 80-150 Hertz was decreased in male and female mice with concurrent reductions in the rate of force development and increases in ½ relaxation time. When expressed as a percentage of maximum force, both males and females also displayed an alcohol-induced leftward shift in the force frequency curve indicative of a type I contractile phenotype. Alcohol enhanced fatigue in both males and females but had no effect on force recovery. Following clearance of alcohol (24-hour post treatment), contractile function was completely restored in females while alcohol treated males experienced sustained reductions in absolute force and had enhanced fatigue compared with male controls.ConclusionsIn the presence of alcohol, both males and females exhibited significant declines in muscle force production and enhanced fatigue; however, following complete clearance of the alcohol, females recovered all functional parameters, while males did not.
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Project description:Bovine male castration increases the levels of serum branched chain amino acids via small intestinal amino acid metabolism.
| PRJEB19502 | ENA
Project description:Olfactory experience can alter the molecular and cellular composition of chemosensory neurons within the olfactory sensory epithelia of mice. We sought to investigate the scope of cellular and molecular changes within a mouse's olfactory system as a function of its exposure to complex and salient sets of odors: those emitted from members of the opposite sex. We housed mice either separated from members of the opposite sex (sex-separated) or together with members of the opposite sex (sex-combined) until six months of age, resulting in the generation of four cohorts of mice. From each mouse, the main olfactory epithelium (MOE), vomeronasal organ (VNO), and olfactory bulb (OB) were removed and RNA-extracted. A total of 36 RNA samples, representing three biological replicates per sex/condition/tissue combination, were analyzed for integrity and used to prepare RNA-seq libraries, which were subsequently analyzed via qPCR for the presence of tissue- or sex-specific markers. Libraries were paired-end sequenced to a depth of ~20 million fragments per replicate and the data were analyzed using the Tuxedo suite.
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