ASU Electronic Theses and Dissertations
This collection includes most of the ASU Theses and Dissertations from 2011 to present. ASU Theses and Dissertations are available in downloadable PDF format; however, a small percentage of items are under embargo. Information about the dissertations/theses includes degree information, committee members, an abstract, supporting data or media.
In addition to the electronic theses found in the ASU Digital Repository, ASU Theses and Dissertations can be found in the ASU Library Catalog.
Dissertations and Theses granted by Arizona State University are archived and made available through a joint effort of the ASU Graduate College and the ASU Libraries. For more information or questions about this collection contact or visit the Digital Repository ETD Library Guide or contact the ASU Graduate College at gradformat@asu.edu.
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- All Subjects: Biology
- Creators: Neisewander, Janet L
- Creators: Robert, Jason
Description
This study aims to unearth monological and monocultural discourses buried under the power of the dominant biomedical model governing the HIV/AIDS debate. The study responds to an apparent consensus, rooted in Western biomedicine and its "standardizations of knowledge," in the production of the current HIV/AIDS discourse, especially in Sub-Saharan Africa. As a result, biomedicine has become the dominant actor (in) writing and rewriting discourse for the masses while marginalizing other forms of medical knowledge. Specifically, in its development, the Western biomedical model has arguably isolated the disease from its human host and the social experiences that facilitate the disease's transmission, placing it in the realm of laboratories and scientific experts and giving full ownership to Western medical discourse. Coupled with Western assumptions about African culture that reproduce a one-sided discourse informing the social construction of HIV/AIDS in Africa, this Western monopoly thus constrained the extent and efficacy of international prevention efforts. In this context, the goal for this study is not to demonize the West and biomedicine in general. Rather, this study seeks an alternative and less monolithic understanding currently absent in scientific discourses of HIV/AIDS that frequently elevates Western biomedicine over indigenous medicine; the Western expert over the local. The study takes into account the local voices of Sub-Saharan Africa and how the system has affected them, this study utilizes a Foucauldian approach to analyze discourse as a way to explore how certain ways of knowledge are formed in relation to power. This study also examines how certain knowlege is maintaned and reinforced within specific discourses.
ContributorsAbdalla, Mohamed (Author) / Jacobs, Bertram (Thesis advisor) / Robert, Jason (Committee member) / Klimek, Barbara (Committee member) / Arizona State University (Publisher)
Created2014
Description
Cognitive function is multidimensional and complex, and research indicates that it is impacted by age, lifetime experience, and ovarian hormone milieu. One particular domain of cognitive function that is susceptible to age-related decrements is spatial memory. Cognitive practice can affect spatial memory when aged in both males and females, and in females alone ovarian hormones have been found to alter spatial memory via modulating brain microstructure and function in many of the same brain areas affected by aging. The research in this dissertation has implications that promote an understanding of the effects of cognitive practice on aging memory, why males and females respond differently to cognitive practice, and the parameters and mechanisms underlying estrogen's effects on memory. This body of work suggests that cognitive practice can enhance memory when aged and that estrogen is a probable candidate facilitating the observed differences in the effects of cognitive practice depending on sex. This enhancement in cognitive practice effects via estrogen is supported by data demonstrating that estrogen enhances spatial memory and hippocampal synaptic plasticity. The estrogen-facilitated memory enhancements and alterations in hippocampal synaptic plasticity are at least partially facilitated via enhancements in cholinergic signaling from the basal forebrain. Finally, age, dose, and type of estrogen utilized are important factors to consider when evaluating estrogen's effects on memory and its underlying mechanisms, since age alters the responsiveness to estrogen treatment and the dose of estrogen needed, and small alterations in the molecular structure of estrogen can have a profound impact on estrogen's efficacy on memory. Collectively, this dissertation elucidates many parameters that dictate the outcome, and even the direction, of the effects that cognitive practice and estrogens have on cognition during aging. Indeed, many parameters including the ones described here are important considerations when designing future putative behavioral interventions, behavioral therapies, and hormone therapies. Ideally, the parameters described here will be used to help design the next generation of interventions, therapies, and nootropic agents that will allow individuals to maintain their cognitive capacity when aged, above and beyond what is currently possible, thus enacting lasting improvement in women's health and public health in general.
ContributorsTalboom, Joshua S (Author) / Bimonte-Nelson, Heather A. (Thesis advisor) / Conrad, Cheryl D. (Committee member) / Neisewander, Janet L (Committee member) / West, Stephen G. (Committee member) / Arizona State University (Publisher)
Created2011
Description
Greater than 11% of the total population of Americans age 12 and older were illicit drug users with close to 1 million suffering from cocaine use disorder in 2017 alone (SAMHSA, 2017), yet there are no effective pharmacological treatments for this disorder. Previous research from the Neisewander Laboratory in male rats found that administration of a 5-HT1BR agonist facilitates cocaine intake when given prior to a daily self-administration session, while inhibiting cocaine intake and attenuating drug-seeking behavior following 21 days of protracted abstinence, yet it is not known whether such effects are observed in female rats. Women face unique challenges in all phases of the drug addiction cycle. With respect to active drug-taking (i.e., the maintenance phase), women tend to increase their rate of consumption more rapidly than men, and female rats acquire cocaine self-administration faster than males. In part, this is due to ovarian hormone influences on the reinforcing properties of cocaine, where peak levels of endogenous estrogen hormones correspond to an increase in cocaine intake. In this study, we investigated the effects of CP94253, a selective 5HT1BR agonist, on cocaine intake across all phases of the estrous cycle in female rats. The rats were trained to self-administer cocaine (0.75 mg/kg, IV) on a fixed ratio (FR) 5 schedule of reinforcement and daily vaginal smears were taken after each session to monitor the estrous cycle. Rats were pretreated with CP 94,253 (5.6 mg/kg, IP) or vehicle prior to separate tests during each estrous cycle phase and were then either given 1-h access to 0.75 mg/kg cocaine followed by 1-h access to 0.375 mg/kg cocaine or 1-h access to 0.1875 mg/kg cocaine followed by 1-h access to 0.075 mg/kg cocaine. Similar to males, CP 94,253 decreased cocaine intake in females at intermediate doses, however, the estrous cycle phase did not alter this effect.
ContributorsScott, Samantha Nicola (Author) / Neisewander, Janet L (Thesis advisor) / Olive, Michael F (Committee member) / Orchinik, Miles (Committee member) / Arizona State University (Publisher)
Created2019
Description
Cocaine induces long-lasting changes in mesolimbic ‘reward’ circuits of the brain after cessation of use. These lingering changes include the neuronal plasticity that is thought to underlie the chronic relapsing nature of substance use disorders. Genes involved in neuronal plasticity also encode circular RNAs (circRNAs), which are stable, non-coding RNAs formed through the back-splicing of pre-mRNA. The Homer1 gene family, which encodes proteins associated with cocaine-induced plasticity, also encodes circHomer1. Based on preliminary evidence from shows cocaine-regulated changes in the ratio of circHomer1 and Homer1b mRNA in the nucleus accumbens (NAc), this study examined the relationship between circHomer1 and incentive motivation for cocaine by using different lengths of abstinence to vary the degree of motivation. Male and female rats were trained to self-administer cocaine (0.75 mg/kg/infusion, IV) or received a yoked saline infusion. Rats proceeded on an increasingly more difficult variable ratio schedule of lever pressing until they reached a variable ratio 5 schedule, which requires an average of 5 lever presses, and light and tone cues were delivered with the drug infusions. Rats were then tested for cocaine-seeking behavior in response to cue presentations without drug delivery either 1 or 21 days after their last self-administration session. They were sacrificed immediately after and circHomer1 and Homer1b expression was then measured from homogenate and synaptosomal fractions of NAc shell using RT-qPCR. Lever pressing during the cue reactivity test increased from 1 to 21 days of abstinence as expected. Results showed no group differences in synaptic circHomer1 expression, however, total circHomer1 expression was downregulated in 21d rats compared to controls. Lack of change in synaptic circHomer1 was likely due to trends toward different temporal changes in males versus females. Total Homer1b expression was higher in females, although there was no effect of cocaine abstinence. Further research investigating the time course of circHomer1 and Homer1b expression is warranted based on the inverse relationship between total circHomer1and cocaine-seeking behavior observed in this study.
ContributorsJohnson, Michael Christian (Author) / Neisewander, Janet L (Thesis advisor) / Perrone-Bizzozero, Nora (Thesis advisor) / Mangone, Marco (Committee member) / Arizona State University (Publisher)
Created2022
Description
Prior to the first successful allogeneic organ transplantation in 1954, virtually every attempt at transplanting organs in humans had resulted in death, and understanding the role of the immune mechanisms that induced graft rejection served as one of the biggest obstacles impeding its success. While the eventual achievement of organ transplantation is touted as one of the most important success stories in modern medicine, there still remains a physiological need for immunosuppression in order to make organ transplantation work. One such solution in the field of experimental regenerative medicine is interspecies blastocyst complementation, a means of growing patient-specific human organs within animals. To address the progression of immune-related constraints on organ transplantation, the first part of this thesis contains a historical analysis tracing early transplant motivations and the events that led to the discoveries broadly related to tolerance, rejection, and compatibility. Despite the advancement of those concepts over time, this early history shows that immunosuppression was one of the earliest limiting barriers to successful organ transplantation, and remains one of the most significant technical challenges. Then, the second part of this thesis determines the extent at which interspecies blastocyst complementation could satisfy modern technical limitations of organ transplantation. Demonstrated in 2010, this process involves using human progenitor cells derived from induced pluripotent stem cells (iPSCs) to manipulate an animal blastocyst genetically modified to lack one or more functional genes responsible for the development of the intended organ. Instead of directly modulating the immune response, the use of iPSCs with interspecies blastocyst complementation could theoretically eliminate the need for immunosuppression entirely based on the establishment of tolerance and elimination of rejection, while also satisfying the logistical demands imposed by the national organ shortage. Although the technology will require some further refinement, it remains a promising solution to eliminate the requirement of immunosuppression after an organ transplant.
ContributorsDarby, Alexis Renee (Author) / Maienschein, Jane (Thesis advisor) / Robert, Jason (Thesis advisor) / Ellison, Karin (Committee member) / Arizona State University (Publisher)
Created2020
Description
This thesis reviews the initial cases of fetal surgery to correct myelomeningocele, a severe form of spina bifida, and discusses the human and social dimensions of the procedure. Myelomeningocele is a fetal anomaly that forms from improper closure of the spinal cord and the tissues that surround it. Physicians perform fetal surgery on a developing fetus, while it is in the womb, to mitigate its impacts. Fetal surgery to correct this condition was first performed experimentally in the mid-1990and as of 2020, it is commonly performed. The initial cases illuminated important human and social dimensions of the technique, including physical risks, psychological dimensions, physician bias, and religious convictions, which affect decision-making concerning this fetal surgery. Enduring questions remain in 2020. The driving question for this thesis is: given those human and social dimensions that surround fetal surgery to correct myelomeningocele, whether and when is the surgery justified? This thesis shows that more research is needed to answer or clarify this question.
ContributorsEllis, Brianna (Author) / Maienschein, Jane (Thesis advisor) / Ellison, Karin (Thesis advisor) / Robert, Jason (Committee member) / Arizona State University (Publisher)
Created2020
Description
Serotonin 1B receptors (5-HT1BRs) are involved in cocaine reward via regulating activity of dopamine neurons. The 5-HT1BR agonist CP-94,253 or 5-HT1BR overexpression in the nucleus accumbens shell (NAcSh) enhances cocaine intake during maintenance of daily self-administration (SA) but inhibits intake after 21 days of abstinence in male rats. My central hypothesis is that CP-94,253 acts at 5-HT1BRs located on the terminals of NAcSh GABA neurons that undergo regulatory changes in response to cocaine SA and subsequent abstinence resulting in an abstinence-induced switch in the functional effects of CP-94,253 in both male and female rats. In the first series of experiments, I compared the functional effects of CP-94,253 in female rats to male rats: 1) during maintenance of daily cocaine SA, 2) after 21-60 days abstinence, and 3) during the resumption of cocaine SA after abstinence (i.e. model of relapse). I found that CP-94,253 enhanced cocaine intake and breakpoints on a high-effort progressive ratio schedule of cocaine reinforcement during maintenance regardless of sex. By contrast, CP-94,253 attenuated cocaine intake after 21 days of abstinence and during the relapse test, regardless of sex. These findings suggest: 1) an abstinence-induced inhibitory effect of the 5-HT1BR agonist occurs in both sexes, 2) these inhibitory effects are long-lasting, and 3) the agonist may provide a novel therapeutic for cocaine use disorders. I next used RNAscope in situ hybridization to measure regulatory changes in 5-HT1BR mRNA expression and its co-expression with GABAergic and glutamatergic cell markers in the lateral and medial NAcSh subregions after abstinence from cocaine. I found no significant changes in these measures in either subregion of NAcSh after prolonged abstinence in either sex; however, I did observe that 95% of 5-HT1BR mRNA is co-localized in GABAergic neurons, whereas <2% is co-localized in glutamatergic cells. Future research investigating abstinence-induced, functional changes in 5-HT1BRs in subregions of the NAcSh is an alternate approach to further test my hypothesis. This research is important for the development of 5-HT1BR agonists as putative treatments of cocaine use disorders.
ContributorsScott, Samantha N (Author) / Neisewander, Janet L (Thesis advisor) / Newbern, Jason (Committee member) / Olive, Michael F (Committee member) / Sanabria, Federico (Committee member) / Arizona State University (Publisher)
Created2024