Browsing by Subject "mice"
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Item Binge-eating behavior in mice: influences of restriction and palatability in a limited access model(2009-05-15) Davis, Kristina W.Animal models of bingeing have typically used stress to induce bingeing. A recent model, limited-access to high-fat diet (HFD), has shown that caloric restriction and stress were not required to induce bingeing in rats. This study replicated this model in mice, explored the fat content within the model, and investigated locomotor activation associated with binge-eating. Adult mice were maintained on a restricted feeding (RF) schedule of 2 h/d of access to chow or ad lib access to chow, and then provided limited access to 45% HFD or 84% HFD for 30 min 3 d/ week for 6 total snack sessions. Circadian activity was monitored for RF animals offered 84% HFD, and after 6 snack sessions were complete, allowed continuous access to the 45% HFD or the 84% HFD for two weeks to explore rebound feeding. Bingeing, defined by increasing intakes across days, was reported for mice offered 45% HFD regardless of deprivation state (RF or ad lib), while mice offered 84% HFD only exhibited bingeing when they were restricted. Comparison of male and female mice maintained RF, offered 45% HFD snack, showed that females had higher intake (kcals/g-bw) while ad lib fed mice exhibited no sex differences. Circadian recordings for female RF mice offered 84% HFD showed shifts in activity from the first hour of dark cycle to the hour preceding the snack and supported that offering the HFD produced alterations in food-associated arousal. During rebound, female RF mice given 84% HFD showed the highest intakes in week 1, and then exhibited a marked decline in week 2. The week 1 intake for RF animals were to regain lost body weight and that homeostatic-like intake in week 2 allowed normal body weight maintenance. Results of this investigation support human data that females are more susceptible to binge-type eating disorder, shows that limited access to palatable foods for females under caloric restriction induces changes in circadian activity, and reveals that using mice in this model requires more investigation to optimize binge-behavior. Diet comparisons also suggest that homeostatic and reward mechanisms may have an additive effect on bingeing.Item Bone Canonical WNT/B-Catenin Signaling in Models of Reduced Microgravity(2012-10-25) Macias, Brandon 1979-Human exposure to reduced weightbearing results in bone loss. The rate of bone loss during microgravity exposure is similar to that of a post-menopausal women. In fact, the maintenance of bone mass is intimately dependent on exercise. Therefore, exercise associated mechanical loads to bone tissue are an important countermeasure to prevent disuse-induced bone loss. However, the types of exercise modalities required to prevent such bone loss are unclear. Moreover, how mechanical loading to bone translates into molecular osteogenic signals in bone cells is unknown. Radiation exposure is another potent inducer of bone loss, namely observed on Earth in the clinical setting following radiotherapy procedures. It is expected that long duration space missions outside the protection of Earth?s magnetosphere will result in significant galactic cosmic radiation exposure. However, the magnitude of bone loss resulting from this galactic cosmic radiation exposure is unclear. Moreover, it is unknown if radiation exposure will exacerbate disuse-induced bone loss. Therefore, a series of experiments were designed to determine: 1) Will simulated galactic cosmic radiation exacerbate reduced weightbearing-induced bone loss? 2) Will pharmacological activation of the putative mechanosensing Wnt pathway enhance exercise-induced bone mass gain? To address these questions the experimental study series employed two animal models of reduced weightbearing, hindlimb unloading and partial weightbearing. These model test-beds enabled the evaluation of two novel countermeasures (simulated resistance exercise and glycogen synthase kinase-3 (GSK-3) therapeutic) and simulated exposure to space radiation environments. To test the impact of simulated space radiation (28Si) one study of the series was conducted at Brookhaven National Laboratory. To quantify the impact of the abovementioned countermeasures and space radiation on bone, mechanical testing, peripheral quantitative computed tomography, micro-computed tomography, histomorphometry, and immunohistochemistry served as primary outcome measures. The primary findings are: 1) Low-dose high-LET radiation negativity impacts maintenance of bone mass by lowering bone formation and increasing bone resorption. This impaired bone formation response is in part due to sclerostin induced suppression of Wnt signaling. 2) Combining GSK-3 inhibition with high intensity exercise mitigates cancellous bone loss and restores cortical periosteal growth during disuse.Item Comparison of cecal colonization of Salmonella enterica serotype Typhimurium in white leghorn chicks and Salmonella-resistant mice(2009-05-15) Sivula, Christine PatriciaSalmonellosis is one of the most important bacterial food borne illnesses worldwide. Among the many Salmonella serotypes, Typhimurium is the most commonly implicated serotype in human disease in the United States. A major source of infection for humans is consumption of chicken or egg products that have been contaminated with S. Typhimurium. The breadth of knowledge regarding colonization and persistence factors in the chicken is small when compared to our knowledge of factors that are important for these processes in other species used in Salmonella research, such as cattle and mice. Defining the factors important for these processes in the chick is the first step in decreasing the transmission of Salmonella between animal and human hosts. In this work, we developed a chicken model to identify and study intestinal colonization and persistence factors of Salmonella enterica serovar Typhimurium. We studied the degree of enteric and systemic colonization of wild type S. Typhimurium ATCC14028, one of the most widely studied Typhimurium isolates, in White Leghorn chicks and in Salmonella-resistant CBA/J mice during infection. Furthermore, we determined the distribution of wild type S. Typhimurium and a SPI-1 mutant (invA) during competitive infection in the cecum of 1-week-old chicks and 8-week-old mice. Cell associated, intracellular and luminal distributions of these strains in the cecum were analyzed as total counts in each compartment and also as a competitive index. Localization of S. Typhimurium ATCC14028 and the role of SPI-1 in colonization are well studied in murine models of infection, but comparative infection in chicks with the same strain has not been undertaken previously. We show that the cecal contents are the major site for recovery of S. Typhimurium in the cecum of 1-week-old chicks and Salmonella-resistant mice. We also show that while SPI-1 is important for successful infection in the murine model, it is important only for cell association in the cecum of 1-week-old chicks. Finally, we found that in chicks infected at 1 week of age, bacterial counts in the feces do not reflect those seen in the cecum as they do in mice.Item Contour Collimation Systems to be Used for Murine Irradiation(2013-05-06) Uhlemeyer, James RichardThree collimators were designed and built with mouse irradiation in mind. They were made to have a shapeable aperture that could deliver strange or complex dose shapes to spots on the animals. Current collimators are either custom-built, expensive, or only provide limited dose shapes. These provide self-customizable collimation at a minimum of cost. A mouse holder was also devised to reproducibly hold a mouse under the collimator. Construction of the holder and of each collimator is also covered. Each collimator was analyzed for flaws, holes, and penumbral width across various shapes of interest. A Norelco MG300 X-ray generator at the Texas A&M Nuclear Science Center was used in these tests. The lead collimator had a radial penumbra of 1.2 mm. The clay / lead shot collimator had a radial penumbra of 1.6 mm. The brass collimator had a radial penumbra of 1.75 mm. Vertical and horizontal penumbras are dependent on distance from the center of the beam. All readings are + 0.3 mm according to the resolution of the scanner used in this experiment. Each collimator is useful for different purposes.Item Effects of Bioactive Compounds from Different Potato Genotypes on Prostate Cancer Development in Athymic Nude Mice(2012-07-16) Turner, SarahPhytochemicals are widely noted for their role in chemoprevention. Potato (Solanum tuberosum L.) is the third most important food crop worldwide and is considered a significant source of antioxidants, providing an ideal delivery system for beneficial compounds. The anti-proliferative and pro-apoptotic properties of potato bioactive compounds have been reported in vitro on human prostate cancer cell lines. However, in vivo studies are limited, and more information is needed to determine the chemopreventive properties of potato in the diet. The objective of this study was to evaluate the effects of potato bioactives on prostate cancer in vivo using a mouse model. Athymic nude mice received xenografts of human prostate cancer cells (PC-3) and were administered extracts of potato bioactives from either the white flesh Solanum bulbocastanum (PI243510) or CO112F2-2P/P (purple-flesh Colorado selection), while control mice received water. Neither potato extract provided a significant reduction in tumor growth nor reduced levels of the pro-angiogenic protein VEGF, but the S. bulbocastanum extract reduced expression of metastasis associated protein 1 (MTA1) in tumors, and both potato extracts reduced MTA1 expression in lungs, suggesting the need for further research on the potential chemopreventive or chemotherapeutic properties of potato bioactives.Item Incorporation of analgesics into rodent embryo transfer protocols: assessing the effects on reproductive outcomes(2009-05-15) Burckhardt, Heather AnnSurgical embryo transfer in rodents is a common procedure in today?s research laboratory, although little is known of the effect analgesics may have on not only the recipient female but also the embryos. Two perioperative analgesics, ketoprofen and buprenorphine, were evaluated against a saline control in terms of number of pups born, number of pups weaned, and whether or not a litter was born. Both a uterine approach and an oviduct approach were evaluated. Post-surgical behavior was compared among the three surgical animals in each group, and between the non-surgical analgesic control and its surgical counterpart. Results indicated that ketoprofen and buprenorphine have no effect on the number of pups born, weaned, or litters born when compared to a saline control. Significant differences were found between the non-surgical analgesic control and its surgical counterpart in two behavioral categories; once for ketoprofen (behavior) and once for buprenorphine (physical condition). No other differences were found.Item Prenatal exposure to maternal obesity and SFLT-1 overexpression and cardiovascular function in the adult offspring(2010-03-11) Egle Bytautiene; George R. Saade; Sean Blackwell; Laura Rudkin; Gary D.V. Hankins; Daniel Freeman; Cristianna RastelliniCardiovascular disease is the leading cause of death in the United States. Adult smoking, type II diabetes, and other environments and conditions, have been identified as risk factors for cardiovascular diseases; however, the effects of prenatal development cannot be overlooked. In the 1980s Barker proposed a hypothesis that poor nutrition in the fetal or early neonatal period increases susceptibility to the negative effects of an affluent diet during adulthood. Overall, there is little understanding of the exact mechanisms of the developmental origin of adult disease, but it is recognized that adult disease occur when postnatal environment is considerable different from what fetus experienced while in utero. The obesity epidemic has led to the evaluation of the effect of a high fat nutritional environment on fetal programming. Conversely, recent studies have shown that the maternal prepregnancy weight is a strong independent risk factor for preeclampsia. Preeclampsia by itself has a negative effect on offspring’s future cardiovascular function. It is possible that maternal obesity in conjunction with preeclampsia may emerge as one of the risk for impairment of cardiovascular function in adult life. \r\nThese studies were performed to determine the effect of prepregnancy obesity and sFlt1-induced preeclampsia on cardiovascular function in the offspring in a small animal model. A link between increased blood pressure and amplified vascular reactivity was revealed in offspring born to mothers fed high fat diet and with or without sFlt1 overexpression during pregnancy. In addition, investigation of metabolic, inflammatory and atherosclerotic profiles and determination protein expressions of angiotensin II, as well as its receptors, lead to a conclusion that maternal obesity is a much stronger negative factor influencing offspring’s cardiovascular function than pregnancy complications. Though, if combined together, obesity and preeclampsia have even more detrimental effect. Study also identified possible mechanisms and indicated several directions for therapeutical approaches. \r\nItem Social environment modulates morphine sensitivity: A partial role of vasopressin V1b receptor(2012-08-31) Hofford, Rebecca 1983-Social factors influence drug abuse in adolescents; this is partially attributed to peer pressure in humans. Similarly, using rodent models, some research suggests that social housing condition can influence rodents' drug taking behavior. Despite this, few studies have examined the role that intoxicated peers have on drug-naive cage-mates. This dissertation examined how social environment affects opioid sensitivity and hormone production. This was accomplished by comparing the opioid sensitivity of mice housed in mixed cages (some animals received opioids and some were drug-naive) to cages where all the mice were treated with the same drug (all saline or all morphine). These studies identified an adolescent-specific vulnerability to social environment-induced alteration of morphine sensitivity. Interaction with drug-intoxicated cage-mates enhanced locomotor sensitivity in previously drug-naive males and altered their production of testosterone. Conversely, interaction of morphine experienced mice with drug-naive cage-mates afforded protection from the rewarding properties of morphine. In other words, morphine-treated mice housed with drug-naive cage-mates demonstrated attenuated reward compared to morphine-treated mice housed with other morphine-treated mice. In addition, part of the neurobiological basis of the social-environment effect was identified. Antagonism of V1b receptors decreased morphine reward in morphine-treated mice housed only with other morphine-treated mice. These results suggest a role of vasopressin in the peer influence on drug sensitivity observed in adolescents. This body of work further elucidates the role of peer influence on opioid sensitivity. Future studies should further reveal the role of healthy peer relationships and should aid in combating drug abuse in this at-risk demographic.Item The impact of social stress on acute Theiler's murine encephalitis virus infection.(Texas A&M University, 2004-09-30) Johnson, Robin RaneeStress is known to alter immune function, both in positive and negative ways. The disparate effects of stress on immune function remains an active area of investigation. This thesis investigates how the application of social disruption stress either prior to or concurrent with infection alters the neuropathogenesis of Theiler's murine encephalitis virus. Experiment 1 verified that social disruption prior to infection exacerbated the course of infection. Experiment 2 examined application of social disruption concurrent with infection, and found that this may produce a delay in symptom onset, and possibly a protective effect. Experiment 3 directly compared the two schedules to each other. The previous findings were replicated and expanded with additional measures (both behavioral and physiological) that further verified the earlier findings. Social disruption applied prior to infection resulted in greater behavioral and physiological exacerbation of the disease. Concurrently applied stress remained protective or inhibitory in the disease progression. Timing of stress is one of several quantitative aspects of stress that has been found to impact the stress-immune interaction and should be further investigated.