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There has long been a link tied between obesity and such pathological conditions as nonalcoholic fatty liver disease and type two diabetes. Studies have shown that feeding rats a diet high in fat results in hepatic steatosis and steatohepatitis. Using a novel short term diet of six weeks with male

There has long been a link tied between obesity and such pathological conditions as nonalcoholic fatty liver disease and type two diabetes. Studies have shown that feeding rats a diet high in fat results in hepatic steatosis and steatohepatitis. Using a novel short term diet of six weeks with male adolescent Sprague-Dawley rats, our laboratory sought to investigate the early effects of high fat intake on the liver. Prior findings in our laboratory found that a high fat diet (HFD) leads to nonalcoholic fatty liver disease as well as other symptoms of metabolic syndrome. This study hypothesized that rats fed a 60% HFD for 6 weeks, unlike a high sucrose or standard chow diet, would have an elevated expression of pro-inflammatory cytokines associated with steatohepatitis. TNF-α, TLR4 and XBP1 were chosen for their link to hepatic inflammation. The results of this study found that contrary to the hypothesis, the high fat diet did not induce significant changes in the expression of any inflammatory marker in comparison to a high sucrose or control chow diet.
ContributorsCalhoun, Matthew (Author) / Sweazea, Karen (Thesis director) / Deviche, Pierre (Reviewer) / Barrett, The Honors College (Contributor)
Created2015-05
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Birds have unusually high plasma glucose concentrations compared to mammals of similar size despite their high metabolic rate. While birds use lipids as their main source of energy, it is still unclear how and why they maintain high plasma glucose concentrations. To investigate a potential underlying mechanism, this study looks

Birds have unusually high plasma glucose concentrations compared to mammals of similar size despite their high metabolic rate. While birds use lipids as their main source of energy, it is still unclear how and why they maintain high plasma glucose concentrations. To investigate a potential underlying mechanism, this study looks at the role of lipolysis in glucose homeostasis. The purpose of this study is to examine the effects of decreased glycerol availability (through inhibition of lipolysis) on plasma glucose concentrations in mourning doves. The hypothesis is that decreased availability of glycerol will result in decreased production of glucose through gluconeogenesis leading to reduced plasma glucose concentrations. In the morning of each experiment, mourning doves were collected at the Arizona State University Tempe campus, and randomized into either a control group (0.9% saline) or experimental group (acipimox, 50mg/kg BM). Blood samples were collected prior to treatment, and at 1, 2, and 3 hours post-treatment. At 3 hours, doves were euthanized, and tissue samples were collected for analysis. Acipimox treatment resulted in significant increases in blood glucose concentrations at 1 and 2 hours post- treatment as well as renal triglyceride concentrations at 3 hours post-treatment. Change in plasma free glycerol between 0h and 3h followed an increasing trend for the acipimox treated animals, and a decreasing trend in the saline treated animals. These results do not support the hypothesis that inhibition of lipolysis should decrease blood glycerol and blood glucose levels. Rather, the effects of acipimox in glucose homeostasis appear to differ significantly between birds and mammals suggesting differing mechanisms for glucose homeostasis.
ContributorsKouteib, Soukaina (Author) / Sweazea, Karen (Thesis director) / Deviche, Pierre (Committee member) / Chandler, Douglas (Committee member) / Barrett, The Honors College (Contributor) / School of Life Sciences (Contributor)
Created2015-05
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Description
Neuroinflammation is an important secondary injury response occurring after traumatic brain injury (TBI). Anxiety-like disorders are commonly exacerbated after TBI and are mediated through the amygdala; however, the amygdala remains understudied despite its important contribution in processing emotional and stressful stimuli. Therefore, we wanted to study neuroinflammation after experimental TBI

Neuroinflammation is an important secondary injury response occurring after traumatic brain injury (TBI). Anxiety-like disorders are commonly exacerbated after TBI and are mediated through the amygdala; however, the amygdala remains understudied despite its important contribution in processing emotional and stressful stimuli. Therefore, we wanted to study neuroinflammation after experimental TBI using midline fluid percussion in rodent models. We assessed microglia morphology over time post-injury in two circuit related nuclei of the amygdala, the basolateral amygdala (BLA) and central amygdala of the nucleus (CeA), using skeletal analysis. We also looked at silver staining and glial fibrillary acidic protein (GFAP) to evaluate the role of neuropathology and astrocytosis to evaluate for neuroinflammation in the amygdala. We hypothesized that experimental diffuse TBI leads to microglial activation in the BLA-CeA circuitry over time post-injury due to changes in microglial morphology and increased astrocytosis in the absence of neuropathology. Microglial cell count was found to decrease in the BLA at 1 DPI before returning to sham levels by 28 DPI. No change was found in the CeA. Microglial ramification (process length/cell and endpoints/cell) was found to decrease at 1DPI compared to sham in the CeA, but not in the BLA. Silver staining and GFAP immunoreactivity did not find any evidence of neurodegeneration or activated astrocytes in the respectively. Together, these data indicate that diffuse TBI does not necessarily lead to the same microglial response in the amygdala nuclei, although an alternative mechanism for a neuroinflammatory response in the CeA likely contributes to the widespread neuronal and circuit dysfunction that occurs after TBI.
ContributorsHur, Yerin (Author) / Newbern, Jason (Thesis director) / Thomas, Theresa Currier (Committee member) / Beitchman, Joshua (Committee member) / School of Molecular Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
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Vascular inflammation is a key component for cerebrovascular disease and ischemic injury is suggested to be a significant contributor, resulting in either myocardial ischemia or stroke. A strong inflammatory response is characterized by the release of inflammatory cytokines, thus producing and/or activating pro-inflammatory proteins in the cell. Our previous studies

Vascular inflammation is a key component for cerebrovascular disease and ischemic injury is suggested to be a significant contributor, resulting in either myocardial ischemia or stroke. A strong inflammatory response is characterized by the release of inflammatory cytokines, thus producing and/or activating pro-inflammatory proteins in the cell. Our previous studies have demonstrated that hypoxia plus glucose deprivation (HGD), an in vitro model of ischemia, increases the proinflammatory mediator, cyclooxygenase-2 levels (COX-2), in vascular tissues. Nuclear factor kappa B (NF-κB) activation is an upstream transcription factor of COX-2 and had been suggested to be involved in “sterile” inflammation in experimental stroke models. Mechanisms underlying the development and progression of inflammation in the cerebrovasculature following ischemic injury in human tissue has not been addressed. Thus, the purpose of this study was to examine the impact of HGD on NF-κB expression and activation in human brain vascular smooth muscle cells (HBVSMC). In addition, we assessed pro-inflammatory mediator levels of downstream NF-κB transcription products, COX-2 and iNOS, and level of its upstream receptor, TLR4. Primary HBVSMC at passage 7 were treated with normoxia (room air) or HGD (1% O2). Following exposure to HGD (3h), cells were isolated, homogenized, and total protein content determined. Lysates, either whole cell or nuclear and cytosolic fractions, were prepped for western blot and analysis. Anti-α-smooth muscle actin was used to verify HBVSMC origin and -actin was used as a loading control. NF-κBp65, phosphorylated NF-κBp65, COX-2, and TLR4 protein levels were all measured post HGD. NF-κBp65 total protein was expressed in HBVSMC and a trend for an increase in levels following HGD was observed. Indirect activation of pNF-kBp65 was assessed via nuclear fractionation studies and was increased following HGD. Lamin AC was used to verify nuclear fractionation. Additional findings suggested that HBVSMC expressed TLR4 however, total protein levels of TLR4 were not altered by HGD. COX-2 and iNOS protein levels were also increased following HGD. In conclusion, these studies indicate that HGD alters proinflammatory enzyme levels, potentially by altering NF-κBp65 activation in human vascular smooth muscle cells. Funding Support: University of Arizona Sarver Heart Center and University of Arizona Valley Research Project Grant VRP P1 (RG).
ContributorsRahman, Sanna (Author) / Sweazea, Karen (Thesis director) / Gonzales, Rayna (Committee member) / Li, Yu-Jing (Committee member) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2018-12
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Description
Vascular inflammation plays a key role in the development and progression of cardiovascular disease. High fat diet has been associated with cardiovascular risk (1). Therefore, as poor nutrition and poor diet become more widespread, the number of people at risk to cardiovascular disease increases. We hypothesized that using the cancer

Vascular inflammation plays a key role in the development and progression of cardiovascular disease. High fat diet has been associated with cardiovascular risk (1). Therefore, as poor nutrition and poor diet become more widespread, the number of people at risk to cardiovascular disease increases. We hypothesized that using the cancer drug lenalidomide would reverse the inflammation caused by high fat conditions. Human aortic vascular smooth muscle cells were used as an in vitro model to analyze the effect of lenalidomide on high fat diet induced inflammation. Palmitate, a saturated fatty acid was used to induce inflammation. Since lenalidomide has been shown to inhibit cytokine production and attenuate oxidative stress, we investigated whether lenalidomide alters select markers of vascular inflammation in vascular smooth muscle treated with high fat exposure using palmitate. These markers were cyclooxygenase-2 (COX-2) protein levels, TNF-α pro-inflammatory cytokine levels, and superoxide ions. Lenalidomide (5 µM) reversed COX-2 protein expression in cells exposed to high fat conditions (100 µM palmitate). In conclusion, high fat exposure elicits an inflammatory response in cultured primary human vascular smooth muscle, but this response appears to be independent of local cytokine or ROS production. Lenalidomide, although effective at reversing palmitate-induced COX-2, alone augments the pro-inflammatory mediators, COX-2 and TNF-α as well as promotes oxidative stress independent of high fat exposure in human vascular smooth muscle cells.
ContributorsBartel, Robyn Katherine (Author) / Sweazea, Karen (Thesis director) / DeCourt, Boris (Committee member) / Gonzales, Rayna (Committee member) / Department of Psychology (Contributor) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2017-12
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Description
Proper developmental fidelity ensures uninterrupted progression towards sexual maturity and species longevity. However, early development, the time-frame spanning infancy through adolescence, is a fragile state since organisms have limited mobility and responsiveness towards their environment. Previous studies have shown that damage during development leads to an onset of developmental delay

Proper developmental fidelity ensures uninterrupted progression towards sexual maturity and species longevity. However, early development, the time-frame spanning infancy through adolescence, is a fragile state since organisms have limited mobility and responsiveness towards their environment. Previous studies have shown that damage during development leads to an onset of developmental delay which is proportional to the extent of damage accrued by the organism. In contrast, damage sustained in older organisms does not delay development in response to tissue damage. In the fruit fly, Drosophila melanogaster, damage to wing precursor tissues is associated with developmental retardation if damage is sustained in young larvae. No developmental delay is observed when damage is inflicted closer to pupariation time. Here we use microarray analysis to characterize the genomic response to injury in Drosophila melanogaster in young and old larvae. We also begin to develop tools to examine in more detail, the role that the neurotransmitter dopamine might play in mediating injury-induced developmental delays.
ContributorsContreras Rodriguez, Jesus (Co-author) / Lupone, Teresa (Co-author) / Beckett, Chaz (Co-author) / Almajan, Ashley (Co-author) / Leek, Ty (Co-author) / Hussain, Sabahat (Co-author) / Marsh, Tyler (Co-author) / Broatch, Jennifer (Co-author) / Hackney Price, Jennifer (Thesis director) / Sandrin, Todd (Committee member) / School of Molecular Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
Description

In intracranial aneurysms, multiple factors and biochemical pathways are believed to be involved in the event of a rupture. The epidermal growth factor receptor (EGFR) activation pathway is of particular interest as a way to understand and target the mechanism of rupture due to its established role in cellular proliferation

In intracranial aneurysms, multiple factors and biochemical pathways are believed to be involved in the event of a rupture. The epidermal growth factor receptor (EGFR) activation pathway is of particular interest as a way to understand and target the mechanism of rupture due to its established role in cellular proliferation and inflammation. Furthermore, unfolded protein responses in vascular cells’ endoplasmic reticulum (ER), known as ER stress, have emerged as a potential downstream mechanism by which inflammatory EGFR activation may lead to aneurysm rupture. The purpose of this project was to investigate the role of EGFR inhibition on the aneurysm rupture rate in a preclinical model, investigate the role of ER stress induction on the aneurysm rupture rate, and confirm which cellular phenomenon lies upstream in this mechanistic cascade. Based on analyses of aneurysm rupture rate and gene expression in the Circle of Willis, ER stress and inflammatory unfolded protein responses were found to be downstream of initial EGFR activation, which may be an effective therapeutic target for preventing aneurysm rupture in a clinical setting.

ContributorsPolen, Kyle (Author) / Van Horn, Wade (Thesis director) / Martin, Thomas (Committee member) / Hashimoto, Tomoki (Committee member) / Barrett, The Honors College (Contributor) / School of Molecular Sciences (Contributor) / School of Human Evolution & Social Change (Contributor)
Created2022-12