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The brain is a fundamental target of the stress response that promotes adaptation and survival but the repeated activation of the stress response has the potential alter cognition, emotion, and motivation, key functions of the limbic system. Three structures of the limbic system in particular, the hippocampus, medial prefrontal cortex

The brain is a fundamental target of the stress response that promotes adaptation and survival but the repeated activation of the stress response has the potential alter cognition, emotion, and motivation, key functions of the limbic system. Three structures of the limbic system in particular, the hippocampus, medial prefrontal cortex (mPFC), and amygdala, are of special interest due to documented structural changes and their implication in post-traumatic stress disorder (PTSD). One of many notable chronic stress-induced changes include dendritic arbor restructuring, which reflect plasticity patterns in parallel with the direction of alterations observed in functional imaging studies in PTSD patients. For instance, chronic stress produces dendritic retraction in the hippocampus and mPFC, but dendritic hypertrophy in the amygdala, consistent with functional imaging in patients with PTSD. Some have hypothesized that these limbic region's modifications contribute to one's susceptibility to develop PTSD following a traumatic event. Consequently, we used a familiar chronic stress procedure in a rat model to create a vulnerable brain that might develop traits consistent with PTSD when presented with a challenge. In adult male rats, chronic stress by wire mesh restraint (6h/d/21d) was followed by a variety of behavioral tasks including radial arm water maze (RAWM), fear conditioning and extinction, and fear memory reconsolidation to determine chronic stress effects on behaviors mediated by these limbic structures. In chapter 2, we corroborated past findings that chronic stress caused hippocampal CA3 dendritic retraction. Importantly, we present new findings that CA3 dendritic retraction corresponded with poor spatial memory in the RAWM and that these outcomes reversed after a recovery period. In chapter 3, we also showed that chronic stress impaired mPFC-mediated extinction memory, findings that others have reported. Using carefully assessed behavior, we present new findings that chronic stress impacted nonassociative fear by enhancing contextual fear during extinction that generalized to a new context. Moreover, the generalization behavior corresponded with enhanced functional activation in the hippocampus and amygdala during fear extinction memory retrieval. In chapter 5, we showed for the first time that chronic stress enhanced amygdala functional activation during fear memory retrieval, i.e., reactivation. Moreover, these enhanced fear memories were resistant to protein synthesis interference to disrupt a previously formed memory, called reconsolidation in a novel attempt to weaken chronic stress enhanced traumatic memory. Collectively, these studies demonstrated the plastic and dynamic effects of chronic stress on limbic neurocircuitry implicated in PTSD. We showed that chronic stress created a structural and functional imbalance across the hippocampus, mPFC, and amygdala, which lead to a PTSD-like phenotype with persistent and exaggerated fear following fear conditioning. These behavioral disruptions in conjunction with morphological and functional imaging data reflect a chronic stress-induced imbalance between hippocampal and mPFC regulation in favor of amygdala function overdrive, and supports a novel approach for traumatic memory processing in PTSD.
ContributorsHoffman, Ann (Author) / Conrad, Cheryl D. (Thesis advisor) / Olive, M. Foster (Committee member) / Hammer, Jr., Ronald P. (Committee member) / Sanabria, Federico (Committee member) / Arizona State University (Publisher)
Created2013
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Chronic restraint stress impairs hippocampal-mediated spatial learning and memory, which improves following a post-stress recovery period. Here, we investigated whether brain derived neurotrophic factor (BDNF), a protein important for hippocampal function, would alter the recovery from chronic stress-induced spatial memory deficits. Adult male Sprague-Dawley rats were infused into the hippocampus

Chronic restraint stress impairs hippocampal-mediated spatial learning and memory, which improves following a post-stress recovery period. Here, we investigated whether brain derived neurotrophic factor (BDNF), a protein important for hippocampal function, would alter the recovery from chronic stress-induced spatial memory deficits. Adult male Sprague-Dawley rats were infused into the hippocampus with adeno- associated viral vectors containing the coding sequence for short interfering (si)RNA directed against BDNF or a scrambled sequence (Scr), with both containing the coding information for green fluorescent protein to aid in anatomical localization. Rats were then chronically restrained (wire mesh, 6h/d/21d) and assessed for spatial learning and memory using a radial arm water maze (RAWM) either immediately after stressor cessation (Str-Imm) or following a 21-day post-stress recovery period (Str-Rec). All groups learned the RAWM task similarly, but differed on the memory retention trial. Rats in the Str-Imm group, regardless of viral vector contents, committed more errors in the spatial reference memory domain than did non-stressed controls. Importantly, the typical improvement in spatial memory following recovery from chronic stress was blocked with the siRNA against BDNF, as Str-Rec-siRNA performed worse on the RAWM compared to the non-stressed controls or Str-Rec-Scr. These effects were specific for the reference memory domain as repeated entry errors that reflect spatial working memory were unaffected by stress condition or viral vector contents. These results demonstrate that hippocampal BDNF is necessary for the recovery from stress-induced hippocampal dependent spatial memory deficits in the reference memory domain.
ContributorsOrtiz, J. Bryce (Author) / Conrad, Cheryl D. (Thesis advisor) / Olive, M. Foster (Committee member) / Taylor, Sara (Committee member) / Bimonte-Nelson, Heather A. (Committee member) / Arizona State University (Publisher)
Created2013
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Description
The RAS/MAPK (RAS/Mitogen Activated Protein Kinase) pathway is a highly conserved, canonical signaling cascade that is highly involved in cellular growth and proliferation as well as cell migration. As such, it plays an important role in development, specifically in development of the nervous system. Activation of ERK is indispensable for

The RAS/MAPK (RAS/Mitogen Activated Protein Kinase) pathway is a highly conserved, canonical signaling cascade that is highly involved in cellular growth and proliferation as well as cell migration. As such, it plays an important role in development, specifically in development of the nervous system. Activation of ERK is indispensable for the differentiation of Embryonic Stem Cells (ESC) into neuronal precursors (Li z et al, 2006). ERK signaling has also shown to mediate Schwann cell myelination of the peripheral nervous system (PNS) as well as oligodendrocyte proliferation (Newbern et al, 2011). The class of developmental disorders that result in the dysregulation of RAS signaling are known as RASopathies. The molecular and cell-specific consequences of these various pathway mutations remain to be elucidated. While there is evidence for altered DNA transcription in RASopathies, there is little work examining the effects of the RASopathy-linked mutations on protein translation and post-translational modifications in vivo. RASopathies have phenotypic and molecular similarities to other disorders such as Fragile X Syndrome (FXS) and Tuberous Sclerosis (TSC) that show evidence of aberrant protein synthesis and affect related pathways. There are also well-defined downstream RAS pathway elements involved in translation. Additionally, aberrant corticospinal axon outgrowth has been observed in disease models of RASopathies (Xing et al, 2016). For these reasons, this present study examines a subset of proteins involved in translation and translational regulation in the context of RASopathy disease states. Results indicate that in both of the tested RASopathy model systems, there is altered mTOR expression. Additionally the loss of function model showed a decrease in rps6 activation. This data supports a role for the selective dysregulation of translational control elements in RASopathy models. This data also indicates that the primary candidate mechanism for control of altered translation in these modes is through the altered expression of mTOR.
ContributorsHilbert, Alexander Robert (Author) / Newbern, Jason (Thesis director) / Olive, M. Foster (Committee member) / Bjorklund, Reed (Committee member) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2017-05
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Description

The SARS-CoV-2 (Covid-19) virus has had severe impacts on college students' ways of life. To examine how students were coping and perceiving the Covid-19 pandemic, a secondary analysis of an online survey across the three Arizona public universities investigated students’ knowledge about Covid-19, engagement with preventive strategies, pandemic preparedness and

The SARS-CoV-2 (Covid-19) virus has had severe impacts on college students' ways of life. To examine how students were coping and perceiving the Covid-19 pandemic, a secondary analysis of an online survey across the three Arizona public universities investigated students’ knowledge about Covid-19, engagement with preventive strategies, pandemic preparedness and gauged their risk perception. Results from our analysis indicate that the students were knowledgeable about Covid-19 and were changing their habits and engaging with preventive measures. Results further suggest that students were prepared for the pandemic in terms of resources and were exhibiting high-risk perceptions. The data also revealed that students who were being cautious and engaging with preventive behaviors had a higher risk-perception than individuals who were not. As for individuals who were prepared for the pandemic in terms of supplies, their risk perception was similar to those who did not have supplies. Individuals who were prepared and capable of providing a single caretaker to tend to their sick household members and isolate them in a separate room had a higher risk perception than those who could not. These results can help describe how college students will react to a future significant event, what resources students may be in need of, and how universities can take additional steps to keep their students safe and healthy. The results from this study and recommendations will provide for a stronger and more understanding campus community during times of distress and can improve upon already established university protocols for health crises and even natural disasters.

ContributorsNaqvi, Avina Itrat (Co-author) / Shaikh, Sara (Co-author) / Jehn, Megan (Thesis director) / Adams, Marc (Committee member) / School of Life Sciences (Contributor) / School of Human Evolution & Social Change (Contributor) / Barrett, The Honors College (Contributor)
Created2021-05
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Due to the COVID-19 pandemic, declared in March of 2020, there have been many lifestyle changes which have likely influenced tobacco smoking behavior. Such lifestyle changes include lockdowns, stay at home orders, reduction in social cues related to smoking, increased stress, and boredom among other things. This study utilized a

Due to the COVID-19 pandemic, declared in March of 2020, there have been many lifestyle changes which have likely influenced tobacco smoking behavior. Such lifestyle changes include lockdowns, stay at home orders, reduction in social cues related to smoking, increased stress, and boredom among other things. This study utilized a cross-sectional survey which looked into these behaviors, primarily perceived risk to COVID-19, and determined if there is an association between perceived risk and education level/race. Education level is a proxy for income and material resources, therefore making it more likely that people with lower levels of education have fewer resources and higher perceived risk to negative effects of COVID-19. Additionally, people of color are often marginalized in the medical community along with being the target of heavy advertising by tobacco companies which have likely impacted risk to COVID-19 as well.

ContributorsLodha, Pratishtha (Author) / Leischow, J. Scott (Thesis director) / Pearson, Jennifer (Committee member) / School of Life Sciences (Contributor) / School of Human Evolution & Social Change (Contributor) / Barrett, The Honors College (Contributor)
Created2021-05
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In the United States, clinical testing is monitored by the federal and state governments, held to standards to ensure the safety and efficacy of these tests, as well as maintaining privacy for patients receiving a test. In order for the ABCTL to lawfully operate in the state of Arizona, it

In the United States, clinical testing is monitored by the federal and state governments, held to standards to ensure the safety and efficacy of these tests, as well as maintaining privacy for patients receiving a test. In order for the ABCTL to lawfully operate in the state of Arizona, it had to meet various legal criteria. These major legal considerations, in no particular order, are: Clinical Laboratory Improvement Amendments compliance; FDA Emergency Use Authorization (EUA); Health Insurance Portability and Accountability Act compliance; state licensure; patient, state, and federal result reporting; and liability. <br/>In this paper, the EUA pathway will be examined and contextualized in relation to the ABCTL. This will include an examination of the FDA regulations and policies that affect the laboratory during its operations, as well as a look at the different authorization pathways for diagnostic tests present during the COVID-19 pandemic.

ContributorsJenkins, Landon James (Co-author) / Espinoza, Hale Anna (Co-author) / Filipek, Marina (Co-author) / Ross, Nathaniel (Co-author) / Salvatierra, Madeline (Co-author) / Compton, Carolyn (Thesis director) / Rigoni, Adam (Committee member) / Stanford, Michael (Committee member) / School of Life Sciences (Contributor) / School of Politics and Global Studies (Contributor) / Barrett, The Honors College (Contributor)
Created2021-05
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Description

This thesis project is the result of close collaboration with the Arizona State University Biodesign Clinical Testing Laboratory (ABCTL) to document the characteristics of saliva as a test sample, preanalytical considerations, and how the ABCTL utilized saliva testing to develop swift COVID-19 diagnostic tests for the Arizona community. As of

This thesis project is the result of close collaboration with the Arizona State University Biodesign Clinical Testing Laboratory (ABCTL) to document the characteristics of saliva as a test sample, preanalytical considerations, and how the ABCTL utilized saliva testing to develop swift COVID-19 diagnostic tests for the Arizona community. As of April 2021, there have been over 130 million recorded cases of COVID-19 globally, with the United States taking the lead with approximately 31.5 million cases. Developing highly accurate and timely diagnostics has been an important need of our country that the ABCTL has had tremendous success in delivering. Near the start of the pandemic, the ABCTL utilized saliva as a testing sample rather than nasopharyngeal (NP) swabs that were limited in supply, required highly trained medical personnel, and were generally uncomfortable for participants. Results from literature across the globe showed how saliva performed just as well as the NP swabs (the golden standard) while being an easier test to collect and analyze. Going forward, the ABCTL will continue to develop high quality diagnostic tools and adapt to the ever-evolving needs our communities face regarding the COVID-19 pandemic.

ContributorsSmetanick, Jennifer (Author) / Compton, Carolyn (Thesis director) / Magee, Mitch (Committee member) / School of Life Sciences (Contributor) / Harrington Bioengineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2021-05
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Description

The ASU Biodesign Clinical Testing Laboratory began in March 2020 after the severe acute respiratory syndrome, coronavirus 2, began spreading throughout the world. ASU worked towards implementing  its own efficient way of testing for the virus, in order to assist the university but also keep the communities around it safe.

The ASU Biodesign Clinical Testing Laboratory began in March 2020 after the severe acute respiratory syndrome, coronavirus 2, began spreading throughout the world. ASU worked towards implementing  its own efficient way of testing for the virus, in order to assist the university but also keep the communities around it safe. By developing its own strategy for COVID-19 testing, ASU was on the forefront of research by developing new ways to test for the virus. This process began when research labs at ASU were quickly converted into clinical testing laboratories, which used saliva testing to develop swift COVID-19 diagnostic tests for the Arizona community. The lab developed more accurate and time efficient results, while also converting Nasopharyngeal tests to saliva tests. Not only did this allow for fewer amounts of resources required, but more individuals were able to get tested at faster rates. The ASU Biodesign Clinical Testing Laboratory (ABCTL) was able to accomplish this through the adaptation of previous machines and personnel to fit the testing needs of the community. In the future, the ABCTL will continue to adapt to the ever-changing needs of the community in regards to the unprecedented COVID-19 pandemic. The research collected throughout the past year following the breakout of the COVID-19 pandemic is a reflection of the impressive strategy ASU has created to keep its communities safe, while continuously working towards improving not only the testing sites and functions, but also the ways in which an institution approaches and manages an unfortunate impact on diverse communities.

ContributorsMajhail, Kajol (Co-author) / Smetanick, Jennifer (Co-author) / Anderson, Laura (Co-author) / Ruan, Ellen (Co-author) / Shears, Scott (Co-author) / Compton, Carolyn (Thesis director) / Magee, Mitch (Committee member) / School of Life Sciences (Contributor) / School of Human Evolution & Social Change (Contributor) / Barrett, The Honors College (Contributor)
Created2021-05
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Since the start of the COVID 19 pandemic there has undoubtedly been an increase in social distancing orders, isolation, and overall general stress. The current outbreak has been proven to have a heavy impact on issues involving mental health. Social distancing mandates contributed to isolation, which in turn caused a

Since the start of the COVID 19 pandemic there has undoubtedly been an increase in social distancing orders, isolation, and overall general stress. The current outbreak has been proven to have a heavy impact on issues involving mental health. Social distancing mandates contributed to isolation, which in turn caused a surge in psychiatric disorders, either newly onset or exacerbating preexisting conditions (Torales, et al, 2020). Due to significant alterations in daily life, an increase in physical inactivity has already been proven to lead to deterioration of cardiovascular health (Pecanha et al, 2020). Stay at home orders have prevented otherwise healthy people from keeping up their daily exercise and eating habits, contributing to a heightened amount of mental health and hypertensive related issues.<br/>In addition to these health concerns, the pandemic has put stress upon pharmaceutical management practices. Drug utilization surges have led to an impact on patient care and management which requires careful measures to be taken to reduce the inflow of sick patients (Badreldin and Atallah, 2020). A global drug shortage has been a result of these drug utilizations. Understanding the alterations in the usage of specific medications such as prescription psychotropics, antihypertensive drugs, and antidiabetic agents can aid in population management and drug shortages.

ContributorsCastro, Ana Maria (Author) / Martin, Thomas (Thesis director) / Nunez, Diane (Committee member) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2021-05
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This thesis project is part of a larger collaboration documenting the history of the ASU Biodesign Clinical Testing Laboratory (ABCTL). There are many different aspects that need to be considered when transforming to a clinical testing laboratory. This includes the different types of tests performed in the laboratory. In addition

This thesis project is part of a larger collaboration documenting the history of the ASU Biodesign Clinical Testing Laboratory (ABCTL). There are many different aspects that need to be considered when transforming to a clinical testing laboratory. This includes the different types of tests performed in the laboratory. In addition to the diagnostic polymerase chain reaction (PCR) test that is performed detecting the presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), antibody testing is also performed in clinical laboratories. Antibody testing is used to detect a previous infection. Antibodies are produced as part of the immune response against SARS-CoV-2. There are many different forms of antibody tests and their sensitives and specificities have been examined and reviewed in the literature. Antibody testing can be used to determine the seroprevalence of the disease which can inform policy decisions regarding public health strategies. The results from antibody testing can also be used for creating new therapeutics like vaccines. The ABCTL recognizes the shifting need of the community to begin testing for previous infections of SARS-CoV-2 and is developing new forms of antibody testing that can meet them.

ContributorsRuan, Ellen (Co-author) / Smetanick, Jennifer (Co-author) / Majhail, Kajol (Co-author) / Anderson, Laura (Co-author) / Breshears, Scott (Co-author) / Compton, Carolyn (Thesis director) / Magee, Mitch (Committee member) / School of Life Sciences (Contributor, Contributor) / School of Mathematical and Statistical Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2021-05