Browsing by Subject "rodent"
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Item Comparative Neurotoxicity of Methylmercury and Mercuric Chloride In Vivo and In Vitro(2010-10-12) Thuett, Kerry A.It is impossible to remove methylmercury (MeHg) from biological systems because MeHg is found throughout our environment in many fresh and salt water fish. The consumption of fish is important to human nutrition and health. The mechanism of MeHg neurotoxicity must be understood to minimize adverse exposure consequences. The dissertation objective was to: 1) compare mechanisms of MeHg neurotoxicity between animals exposed as adults and those exposed during gestation, and 2) develop an in vitro test model of in vivo MeHg exposure. Total mercury (Hg) levels in tissue / cells were determined by combustion / trapping / atomic absorption. Cell death was determined by Fluoro-Jade histochemical staining and activated caspase 3 immunohistochemistry for in vivo studies, and Trypan blue exclusion, lactate dehydrogenase activity, and cytotoxicity assays for in vitro studies. Mitochondrial membrane potential (MMP), intracellular calcium ion concentration ([Ca2+]i), and production of reactive oxygen species (ROS) were determined using fluorescence microscopy or microplate reader assays. Young adult C57Bl/6 mice were exposed to a total dose of 0, 1.0, or 5.0 mg/kg body weight MeHg divided over postnatal days (P)35 to 39. Pregnant female mice were exposed to a total does of 0, 0.1, or 1.0 mg/kg body weight MeHg divided over gestational days (G)8 to 18. SY5Y cells were exposed to 0, 0.01, 0.1, or 1.0 ?M MeHg or HgCl2 for 24, 48, or 72 hours. Total Hg in brains of young adult mice, mouse pups, and SY5Y cells accumulated in a dose-dependent manner. Cell death increased in SY5Y cells exposed to the highest concentrations of MeHg and HgCl2 used in this study. Cell death increased in the molecular and granule cerebellar cell layers of young adult mice exposed to the highest doses of MeHg used in this study. P0 mouse pups showed no increase in cell death within the cerebellum following MeHg exposure. Cerebella of mice at P10 exhibited decreased dying cells only in the external germinal layer. Low concentrations of MeHg affected MMP in both in vivo and in vitro studies, but did not result in decreased MMP typically associated with higher MeHg concentrations. [Ca2+]i was increased throughout the in vivo experiments in an age- , sexand brain region-dependent manner. Generation of ROS was decreased in both in vivo and in vitro studies with both the MeHg and HgCl2 (in vitro) treatments. In summary, low and moderate MeHg exposure, both in vivo and in vitro, altered mitochondrial function, Ca2+ homeostasis, and ROS differently than what is reported in the literature for higher MeHg exposure concentrations. SY5Y cells were sensitive to low-levels of MeHg and HgCl2 and responded similarly to cells in the whole animal studies, thus making SY5Y cells realistic candidates for mechanistic MeHg studies. Cell culture and whole animal neuronal functional studies at chronic low-level MeHg exposure are limited. These data suggest that low-levels of MeHg may affect neuronal function. Therefore, further chronic low-level MeHg neuronal functional studies are warranted.Item Field and laboratory studies of venezuelan equine encephalitis virus ecology in Chiapas, Mexico.(2009-03-05) Eleanor Rose Deardorff; Scott WeaverThe emergence of Venezuelan equine encephalitis virus in Chiapas Mexico was examined from a field approach and from a laboratory approach. This virus was not previously associated with equine disease in Mexico. The evolution of the equine virulent phenotype was thought to have resulted in a mosquito vector switch from Culex (Melanoconion) taeniopus to Aedes (Ochlerotatus) taeniorhynchus as a result of land-use changes. Wild rodents and mosquitoes were captured over the course of one year and little evidence of virus circulation was found. Wild rodents from five species were then imported into the lab for experimental evaluation as virus amplifying hosts. It was found that a VEEV strain from the study area may use a variety of rodents as amplifying hosts in the laboratory. Lastly a breeding colony of Culex (Mel.) taeniopus mosquitoes was established and experimentally evaluated for the ability of these mosquitoes to transmit equine virulent VEEV. It was found that equine virulent virus infects and is transmitted by this mosquito with high efficiency and is likely maintained in transmission foci by Culex (Mel) taeniopus during inter-epizootic periods.Item HABITAT SUITABILITY MODELING OF PEROMYSCUS PECTORALIS (WHITE-ANKLED MOUSE) IN VAL VERDE CO., TEXASMorgan, Clint Newman; Dowler, Robert C; Ammerman, Loren K; Negovetich, Nicholas J; Dickison, James WThe goal of this work was to utilize habitat suitability modeling and spool-and-line tracking to delineate habitat use and distribution of the White-ankled mouse (Peromyscus pectoralis), within the Devils River State Natural Area – Big Satan Unit (DRSNA - BSU), in Val Verde County, Texas. Using trapping data from a 21 month period (February 2013 - October 2014), MaxEnt modeling was used to determine which of 7 environmental variables contributed the most to the species distribution at DRSNA - BSU, and a species distribution map was generated. A jackknife test of variable importance determined vegetation series and slope as the highest contributing variables in isolation. Generalized linear modeling was then used to compare trap-line abundance indices to the percentages of individual vegetation series within a buffered area around the trap-line. Positive correlations with higher abundance indices were observed in winter, spring, and fall among a variety of vegetation series. Using spool-and-line tracking, P. pectoralis was determined to be highly mobile indicating that this species is capable of dispersing to areas of greater resource availability. Data suggest that vegetative habitat selection of this species varies seasonally and is likely dependent on the degree of seasonal resource availability within each vegetation type and the trophic ecology of P. pectoralis.Item Mitigating Disuse Bone Loss: Role of Resistance Exercise and Beta-Adrenergic Signaling(2011-08-08) Swift, Joshua MichaelMechanical loading is an integral component to maintaining bone mass during periods of disuse (i.e. bedrest or casting) or reduced weightbearing activity. Recent data has shown a direct relation between the sympathetic nervous system (SNS) and bone metabolism, however the underlying mechanisms responsible for this relationship are unknown. Furthermore, the role that beta adrenergic stimulation during disuse has on cancellous bone mass and microarchitecture have yet to be defined. The central hypothesis of this research is that resistance exercise and beta-1 adrenergic (Adrb1) receptor agonist administration attenuate disuse-associated reductions in metaphyseal bone during 28 days of rodent hindlimb unloading (HU). Study one determined whether an eccentric- (ECC) or combined isometric+eccentric- (ISO+ECC) based contraction paradigm, engaged during hindlimb unloading (HU), mitigates losses in musculoskeletal mass and strength. Both simulated resistance training (SRT) protocols inhibited reductions in disuse-sensitive cancellous bone mass and maintained plantarflexor muscle strength. Study two determined whether combining the anabolic effects of SRT with the anti-resorptive effects of alendronate (ALEN) during HU positively impacts cancellous bone in an additive or synergistic fashion. ALEN significantly inhibited the anabolic response of cancellous bone to SRT during HU. Study three determined whether an Adrb1 receptor agonist (dobutamine; DOB) mitigates disuse-associated losses in bone mass and formation rate (BFR) during HU. DOB administration significantly blunted reductions in bone mineral density (vBMD) by maintaining cancellous BFR. Study four determined if Adrb1 receptor agonist administration during HU results in an attenuation of osteocyte apoptosis within cancellous bone and whether this relates to a decrease in Bax/Bcl-2 mRNA content ratio (pro- and anti-apoptotic proteins). HU significantly increased cancellous bone osteocyte apoptosis and Bax/Bcl-2 mRNA content ratio, which was reduced by the administration of DOB. Collectively, these are the first studies to assess the role of beta-1 adrenergic signaling and resistance exercise in mitigating disuse-induced loss of cancellous bone mass in rodents. The long term goals of this research are to understand the exact molecular mechanisms by which both Adrb1 signaling and high intensity resistance exercise provide beneficial bone effects during prolonged periods of disuse and to apply these findings to current osteoporosis research.