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Fibromyalgia (FM) is a chronic pain condition characterized by debilitating fatigue. This study examined the dynamic relation between interpersonal enjoyment and fatigue in 102 partnered and 74 unpartnered women with FM. Participants provided three daily ratings for 21 days. They rated their fatigue in late morning and at the end

Fibromyalgia (FM) is a chronic pain condition characterized by debilitating fatigue. This study examined the dynamic relation between interpersonal enjoyment and fatigue in 102 partnered and 74 unpartnered women with FM. Participants provided three daily ratings for 21 days. They rated their fatigue in late morning and at the end of the day. Both partnered and unpartnered participants reported their interpersonal enjoyment in the combined familial, friendship, and work domains (COMBINED domain) in the afternoon. Additionally, partnered participants reported their interpersonal enjoyment in the spousal domain. The study was guided by three hypotheses at the within-person level, based on daily diaries: (1) elevated late morning fatigue would predict diminished afternoon interpersonal enjoyment; (2) diminished interpersonal enjoyment would predict elevated end-of-day fatigue; (3) interpersonal enjoyment would mediate the late morning to end-of-day fatigue relationship. In cross-level models, the study explored whether individual differences (between-person) in late morning fatigue and afternoon interpersonal enjoyment would moderate within-person relations from late morning fatigue to afternoon interpersonal enjoyment, and from afternoon interpersonal enjoyment to end-of-day fatigue. Furthermore, it explored whether the hypothesized relationships at the within-person level would also emerge at the between-person level (between-person mediation models). Multilevel structural equation modeling and multilevel modeling were employed for model testing, separately for partnered and unpartnered participants. Within-person mediation models supported that on high fatigue mornings, afternoon interpersonal enjoyment was dampened in the spousal and combined domains in partnered and unpartnered samples. Moreover, low afternoon interpersonal enjoyment in both the spousal and combined domains predicted elevated end-of-day fatigue. Afternoon interpersonal enjoyment mediated the relationship of late morning to end-of-day fatigue in the combined domain but in not the spousal domain. Cross-level moderation analyses showed that individual differences in afternoon spousal enjoyment moderated the day-to-day relation between afternoon spousal enjoyment and end-of-day fatigue. Finally, the mediational chain was not observed at the between-person level. These findings suggest that preserving interpersonal enjoyment in non-spousal relations limits within-day increases in FM fatigue. They highlight the importance of examining domain-specificity in interpersonal enjoyment when studying fatigue, and suggest that targeting enjoyment in social relations may improve the efficacy of existing treatments.
ContributorsYeung, Wan (Author) / Aiken, Leona S. (Thesis advisor) / Davis, Mary C. (Thesis advisor) / Mackinnon, David P (Committee member) / Zautra, Alex J (Committee member) / Arizona State University (Publisher)
Created2013
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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

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
Female infertility can present a significant challenge to quality of life. To date, few, if any investigations have explored the process by which women adapt to premature ovarian insufficiency (POI), a specific type of infertility, over time. The current investigation proposed a bi-dimensional, multi-factor, model of adjustment characterized by the

Female infertility can present a significant challenge to quality of life. To date, few, if any investigations have explored the process by which women adapt to premature ovarian insufficiency (POI), a specific type of infertility, over time. The current investigation proposed a bi-dimensional, multi-factor, model of adjustment characterized by the identification of six latent factors representing personal attributes (resilience resources and vulnerability), coping (adaptive and maladaptive) and outcomes (distress and wellbeing). Measures were collected over the period of one year; personal attributes were assessed at Time 1, coping at Time 2 and outcomes at Time 3. It was hypothesized that coping factors would mediate associations between personal attributes and outcomes. Confirmatory Factor Analysis (CFA), simple regressions and single mediator models were utilized to test study hypotheses. Overall, with the exception of coping, the factor structure was consistent with predictions. Two empirically derived coping factors, and a single standalone strategy, avoidance, emerged. The first factor, labeled "approach coping" was comprised of strategies directly addressing the experience of infertility. The second was comprised of strategies indicative of "letting go /moving on." Only avoidance significantly mediated the association between vulnerability and distress.
ContributorsDriscoll, Mary (Author) / Davis, Mary C. (Thesis advisor) / Aiken, Leona S. (Committee member) / Luecken, Linda J. (Committee member) / Zautra, Alex J. (Committee member) / Arizona State University (Publisher)
Created2011
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Description
Current models of pain coping typically focus on how pain contributes to poor physical and psychological functioning. Researchers have argued that this focus on the negative consequences is too narrow and does not account for times when individuals are able to maintain meaningful functioning despite their pain. Thus, the current

Current models of pain coping typically focus on how pain contributes to poor physical and psychological functioning. Researchers have argued that this focus on the negative consequences is too narrow and does not account for times when individuals are able to maintain meaningful functioning despite their pain. Thus, the current study sought to investigate the day-to-day processes that both help and hinder recovery from pain and persistence towards daily goals. Specifically, the present study tested: a) a two-factor model of risk and resilience “factors” that capture key processes across affective, cognitive and social dimensions of functioning, and b) whether the relation between morning pain and end-of-day physical disability is mediated by increases in these afternoon risk and resilience factors. Within-day study measures were collected for 21 days via an automated phone system from 220 participants with Fibromyalgia. The results of multi-level confirmatory factor analysis indicated that, consistent with prediction, risk and resilience do constitute two factors. Findings from multilevel structural equation models also showed resilience factor mediated the link between late morning increases in pain and end-of-day disability, in line with hypotheses. Although the vulnerability factor as a whole did not mediate the within-day link between pain and disability, pain-catastrophizing individually did serve as a significant mediator of this relation. This study was the first to empirically test a within-day latent factor model of resilience and vulnerability and the first to capture the multidimensional nature of the pain experience by examining mechanisms across affective, cognitive and social domains of functioning. The findings of the current study suggest that in addition to studying the processes by which pain has a negative influence on the lives of pain sufferers, our understanding of the pain adaptation process can be further improved by concurrently examining mechanisms that motivate individuals to overcome the urge to avoid pain and to function meaningfully despite it.
ContributorsThummala, Kirti (Author) / Davis, Mary C. (Thesis advisor) / Doane, Leah (Committee member) / Karoly, Paul (Committee member) / Barrera, Manuel (Committee member) / Arizona State University (Publisher)
Created2018
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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
Major Depressive Disorder (MDD) is a widespread mood disorder that affects more than 300 million people worldwide and yet, high relapse rates persist. This current study aimed to use an animal model for depression, unpredictable intermittent restraint (UIR), to investigate changes in a subset of neurons within the hippocampus, a

Major Depressive Disorder (MDD) is a widespread mood disorder that affects more than 300 million people worldwide and yet, high relapse rates persist. This current study aimed to use an animal model for depression, unpredictable intermittent restraint (UIR), to investigate changes in a subset of neurons within the hippocampus, a region of high susceptibility in MDD. Adult male and female Sprague-Dawley rats were randomly assigned to four treatment groups based on sex (n = 48, n = 12/group). Half of the rats underwent UIR that involved restraint with orbital shaking (30 min or 1 h) for 2-6 consecutive days, followed by one or two days of no stressors; the other half of the rats were undisturbed (CON). UIR rats were stressed for 28 days (21 days of actual stressors) before behavioral testing began with UIR continuing between testing days for nearly 70 days. Rats were then euthanized between 9 and 11 days after the last UIR session. Brains were processed for Golgi stain and long-shaft (LS) neurons within the hippocampal CA3a and CA3b regions were quantified for dendritic complexity using a Camera Lucida attachment. Our findings failed to support our hypothesis that UIR would produce apical dendritic retraction in CA3 hippocampal LS neurons in both males and females. Given that UIR failed to produce CA3 apical dendritic retraction in males, which is commonly observed in the literature, we discuss several reasons for these findings including, time from the end of UIR to when brains were sampled, and the effects of repeated cognitive testing. Given our published findings that UIR impaired spatial ability in males, but not females, we believe that UIR holds validity as a chronic stress paradigm, as UIR attenuated body weight gain in both males and females and produced reductions in thymus gland weight in UIR males. These findings corroborate UIR as an effective stressor in males and warrant further research into the timing of UIR-induced changes in hippocampal CA3 apical dendritic morphology.
ContributorsReynolds, Cindy Marie (Author) / Conrad, Cheryl D. (Thesis director) / Olive, M. Foster (Committee member) / School of Molecular Sciences (Contributor) / Department of English (Contributor) / Barrett, The Honors College (Contributor)
Created2020-12
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Description
Major Depressive Disorder (MDD) affects over 300 million people worldwide, with the hippocampus showing decreased volume and activity in patients with MDD. The current study investigated whether a novel preclinical model of depression, unpredictable intermittent restraint (UIR), would decrease hippocampal neuronal dendritic complexity. Adult Sprague Dawley rats (24 male, 24

Major Depressive Disorder (MDD) affects over 300 million people worldwide, with the hippocampus showing decreased volume and activity in patients with MDD. The current study investigated whether a novel preclinical model of depression, unpredictable intermittent restraint (UIR), would decrease hippocampal neuronal dendritic complexity. Adult Sprague Dawley rats (24 male, 24 female) were equally divided into 4 groups: control males (CON-M), UIR males (UIR-M), control females (CON-F) and UIR females (UIR-F). UIR groups received restraint and shaking on an orbital shaker on a randomized schedule for 30 or 60 minutes/day for two to six days in a row for 26 days (21 total UIR days) before behavioral testing commenced. UIR continued and was interspersed between behavioral test days. At the end of behavioral testing, brains were processed. The behavior is published and not part of my honor’s thesis; my contribution involved quantifying and analyzing neurons in the hippocampus. Several neuronal types are found in the CA3 subregion of the hippocampus and I focused on short shaft (SS) neurons, which show different sensitivities to stress than the more common long shaft (LS) variety. Brains sections were mounted to slides and Golgi stained. SS neurons were drawn using a microscope with camera lucida attachment and quantified using the number of bifurcations and dendritic intersections as metrics for dendritic complexity in the apical and basal areas separately. The hypothesis that SS neurons in the CA3 region of the hippocampus would exhibit apical dendritic simplification in both sexes after UIR was not supported by our findings. In contrast, following UIR, SS apical dendrites were more complex in both sexes compared to controls. Although unexpected, we believe that the UIR paradigm was an effective stressor, robust enough to illicit neuronal adaptations. It appears that the time from the end of UIR to when the brain tissue was collected, or the post-stress recovery period, and/or repeated behavioral testing may have played a role in the observed increased neuronal complexity. Future studies are needed to parse out these potential effects.
ContributorsAcuna, Amanda Marie (Author) / Conrad, Cheryl (Thesis director) / Corbin, William (Committee member) / Olive, M. Foster (Committee member) / School of Life Sciences (Contributor) / Department of Psychology (Contributor) / Barrett, The Honors College (Contributor)
Created2020-12