Matching Items (994)
Description
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
Description
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
Description
Females are highly vulnerable to the effects of methamphetamine, and understanding the mechanisms of this is critical to addressing methamphetamine use as a public health issue. Hormones may play a role in methamphetamine sensitivity; thus, the fluctuation of various endogenous peptides during the postpartum experience is of interest. This honors thesis project explored the relation between anxiety-like behavior, as measured by activity in an open field, and conditioned place preference to methamphetamine in female versus male rats. The behavior of postpartum as well as virgin female rats was compared to that of male rats. There was not a significant difference between males and females in conditioned place preference to methamphetamine, yet females showed higher locomotor activity in response to the drug as well as increased anxiety-like behavior in open field testing as compared to males. Further study is vital to comprehending the complex mechanisms of sex differences in methamphetamine addiction.
ContributorsBaker, Allison Nicole (Author) / Olive, M. Foster (Thesis director) / Presson, Clark (Committee member) / Hansen, Whitney (Committee member) / Department of Psychology (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
Description
Introduction: Human papillomavirus (HPV) infection is seen in up to 90% of cases of cervical cancer, the third leading cancer cause of death in women. Current HPV screening focuses on only two HPV types and covers roughly 75% of HPV-associated cervical cancers. A protein based assay to test for antibody biomarkers against 98 HPV antigens from both high and low risk types could provide an inexpensive and reliable method to screen for patients at risk of developing invasive cervical cancer. Methods: 98 codon optimized, commercially produced HPV genes were cloned into the pANT7_cGST vector, amplified in a bacterial host, and purified for mammalian expression using in vitro transcription/translation (IVTT) in a luminescence-based RAPID ELISA (RELISA) assay. Monoclonal antibodies were used to determine immune cross-reactivity between phylogenetically similar antigens. Lastly, several protein characteristics were examined to determine if they correlated with protein expression. Results: All genes were successfully moved into the destination vector and 86 of the 98 genes (88%) expressed protein at an adequate level. A difference was noted in expression by gene across HPV types but no correlation was found between protein size, pI, or aliphatic index and expression. Discussion: Further testing is needed to express the remaining 12 HPV genes. Once all genes have been successfully expressed and purified at high concentrations, DNA will be printed on microscope slides to create a protein microarray. This microarray will be used to screen HPV-positive patient sera for antibody biomarkers that may be indicative of cervical cancer and precancerous cervical neoplasias.
ContributorsMeshay, Ian Matthew (Author) / Anderson, Karen (Thesis director) / Magee, Mitch (Committee member) / Katchman, Benjamin (Committee member) / Barrett, The Honors College (Contributor) / School of Life Sciences (Contributor)
Created2015-05
Description
microRNAs (miRNAs) are short ~22nt non-coding RNAs that regulate gene output at the post-transcriptional level. Via targeting of degenerate elements primarily in 3'untranslated regions (3'UTR) of mRNAs, miRNAs can target thousands of varying genes and suppress their protein translation. The precise mechanistic function and bio- logical role of miRNAs is not fully understood and yet it is a major contributor to a pleth- ora of diseases, including neurological disorders, muscular disorders, and cancer. Cer- tain model organisms are valuable in understanding the function of miRNA and there- fore fully understanding the biological significance of miRNA targeting. Here I report a mechanistic analysis of miRNA targeting in C. elegans, and a bioinformatic approach to aid in further investigation of miRNA targeted sequences. A few of the biologically significant mechanisms discussed in this thesis include alternative polyadenylation, RNA binding proteins, components of the miRNA recognition machinery, miRNA secondary structures, and their polymorphisms. This thesis also discusses a novel bioinformatic approach to studying miRNA biology, including computational miRNA target prediction software, and sequence complementarity. This thesis allows a better understanding of miRNA biology and presents an ideal strategy for approaching future research in miRNA targeting.
ContributorsWeigele, Dustin Keith (Author) / Mangone, Marco (Thesis director) / Katchman, Benjamin (Committee member) / Barrett, The Honors College (Contributor) / Department of Chemistry and Biochemistry (Contributor) / School of Life Sciences (Contributor)
Created2014-12
Description
An introduction to neuroscientific thought aimed at an audience that is not educated in biology. Meant to be readable and easily understood by anyone with a high school education. The first section is completed in its entirety, with outlines for the proposed final sections to be completed over the next few years.
ContributorsNelson, Nicholas Alan (Author) / Olive, M. Foster (Thesis director) / Brewer, Gene (Committee member) / Barrett, The Honors College (Contributor) / Department of Psychology (Contributor) / School of Life Sciences (Contributor) / School of Historical, Philosophical and Religious Studies (Contributor)
Created2014-05
Description
With the new independence of adulthood, college students are a group susceptible to adopting unsupported, if not harmful, health practices. A survey of Arizona State University undergraduate students (N=200) was conducted to evaluate supplement use, trust in information sources, and beliefs about supplement regulation. Of those who reported using supplements, college students most frequently received information from friends and family. STEM majors in fields unrelated to health who were taking a supplement were found to be less likely to receive information about the supplement from a medical practitioner than those in health fields or those in non-STEM majors (-26.9%, p=0.018). STEM majors in health-related fields were 15.0% more likely to treat colds and/or cold symptoms with research-supported methods identified from reliable sources, while non-health STEM and non-STEM majors were more likely to take unsupported cold treatments (p=0.010). Surveyed students, regardless of major, also stated they would trust a medical practitioner for supplement advice above other sources (88.0%), and the majority expressed a belief that dietary supplements are approved/regulated by the government (59.8%).
ContributorsPerez, Jacob Tanner (Author) / Hendrickson, Kirstin (Thesis director) / Lefler, Scott (Committee member) / College of Liberal Arts and Sciences (Contributor) / School of Molecular Sciences (Contributor) / Department of Physics (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
Description
As research progresses in the field of vaccinology, momentum has been gained to develop an efficacious and efficient dengue virus (DV) vaccine for all four serotypes. Dengue viral outbreaks across the world have called for a vaccine campaign. However, due to anti--"body dependent enhancement of infection, dengue virus has provided Researchers with challenges in developing a safe vaccine. Currently, there are a handful of vaccine candidates in clinical trial, but live chimeric attenuated vaccines dominate them. There are associated risks with using a live chimeric attenuated vaccine, but they are less expensive to generate and seem to provide a high immune response. Subunit vaccines are safer to use and can provide full protection for several years with then use of adjuvants and a booster shot. As a result, our lab is interested in pursuing this route to produce an effective dengue vaccine. The main target for a dengue subunit vaccine is the envelope protein, which is known to be an important recognition site by neutralizing antibodies. Therefore, expression of a recombinant envelope protein in a prokaryotic expression system is useful to study the immune response in vivo. This could be taken a step further and recombinant dengue envelope proteins can be expressed by a eukaryote to help generate hypotheses and insight to create a successful dengue virusn subunit vaccine.
ContributorsRiley, Jade (Author) / Reyes del Valle, Jorge (Thesis director) / Mason, Hugh (Committee member) / Katchman, Benjamin (Committee member) / Barrett, The Honors College (Contributor)
Created2013-05
ContributorsChandler, N. Kayla (Author) / Neisewander, Janet (Thesis director) / Sanabria, Federico (Committee member) / Olive, M. Foster (Committee member) / Barrett, The Honors College (Contributor) / College of Liberal Arts and Sciences (Contributor)
Created2013-05
Description
I propose that norms regulate behaviors that negatively impact an individual's survival and reproduction. But because monitoring and enforcing of norms can be costly, individuals should be selective about which norms they police and under what circumstances they should do so. Two studies tested this idea by experimentally activating fitness-relevant motives and having participants answer questions about the policing of norms. The first study examined a norm prescribing respect for status and another proscribing sexual coercion. Results from Study 1 failed to support the hypotheses; activating a status-seeking motive did not have the predicted effects on policing of the respect-status norm nor did activating a mating motive have the predicted effects on policing of the respect-status norm or anti-coercion norm. Study 2 examined two new norms, one prescribing that people stay home when sick and the other proscribing people from having sex with another person's partners. Study 2 also manipulated whether self or others were the target of the policing. Study 2 failed to provide support; a disease avoidance motive failed to have effects on policing of the stay home when sick norm. Individuals in a relationship under a mating motive wanted less policing of others for violation of the mate poaching norm than those in a baseline condition, opposite of the predicted effects.
ContributorsSmith, M. Kristopher (Author) / Neuberg, L. Steven (Thesis director) / Presson, Clark (Committee member) / Hruschka, J. Daniel (Committee member) / Barrett, The Honors College (Contributor) / College of Liberal Arts and Sciences (Contributor)
Created2013-05