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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
Rasopathies are a family of developmental syndromes that exhibit craniofacial abnormalities, cognitive disabilities, developmental delay and increased risk of cancer. However, little is known about the pathogenesis of developmental defects in the nervous system. Frequently, gain-of-function mutations in the Ras/Raf/MEK/ERK cascade (aka ERK/MAPK) are associated with the observed pathogenesis. My

Rasopathies are a family of developmental syndromes that exhibit craniofacial abnormalities, cognitive disabilities, developmental delay and increased risk of cancer. However, little is known about the pathogenesis of developmental defects in the nervous system. Frequently, gain-of-function mutations in the Ras/Raf/MEK/ERK cascade (aka ERK/MAPK) are associated with the observed pathogenesis. My research focuses on defining the relationship between increased ERK/MAPK signaling and its effects on the nervous system, specifically in the context of motor learning. Motor function depends on several neuroanatomically distinct regions, especially the spinal cord, cerebellum, striatum, and cerebral cortex. We tested whether hyperactivation of ERK/MAPK specifically in the cortex was sufficient to drive changes in motor function. We used a series of genetically modified mouse models and cre-lox technology to hyperactivate ERK/MAPK in the cerebral cortex. Nex:Cre/NeuroD6:Cre was employed to express a constitutively active MEK mutation throughout all layers of the cerebral cortex from an early stage of development. RBP4:Cre, caMEK only exhibited hyper activation in cortical glutamatergic neurons responsible for cortical output (neurons in layer V of the cerebral cortex). First, the two mouse strains were tested in an open field paradigm to assess global locomotor abilities and overall fitness for fine motor tasks. Next, a skilled motor reaching task was used to evaluate motor learning capabilities. The results show that Nex:Cre/NeuroD6:Cre, caMEK mutants do not learn the motor reaching task, although they performed normally on the open field task. Preliminary results suggest RBP4:Cre, caMEK mutants exhibit normal locomotor capabilities and a partial lack of learning. The difference in motor learning capabilities might be explained by the extent of altered connectivity in different regions of the corticospinal tract. Once we have identified the neuropathological effects of various layers in the cortex we will be able to determine whether therapeutic interventions are sufficient to reverse these learning defects.
ContributorsRoose, Cassandra Ann (Author) / Newbern, Jason M. (Thesis director) / Olive, Foster (Committee member) / Bjorklund, Reed (Committee member) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2016-12
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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
Depression, anxiety, and suicidal thoughts or actions are on the rise in adolescents (National Institute of Mental Health, 2015; Bridge, Asti, & Horowitz, 2015). Parents, school administrators, and therapists are searching for resiliency factors with in at-risk groups to aid students in need. In previous work, Luthar and Zigler (1992)

Depression, anxiety, and suicidal thoughts or actions are on the rise in adolescents (National Institute of Mental Health, 2015; Bridge, Asti, & Horowitz, 2015). Parents, school administrators, and therapists are searching for resiliency factors with in at-risk groups to aid students in need. In previous work, Luthar and Zigler (1992) reported that intelligent youth are more resilient than less intelligent youth under low stress conditions but they lose their advantage under high stress conditions. This study examined whether intelligence (reflected in grade point average; GPA) and maladaptive (internalizing and externalizing symptoms) behaviors are negatively related in adolescents, and tested whether level of stress, reflected in emotion regulation and friendship quality, moderated that association. It also probed whether the relationships differ by gender. Sixth-graders (N=506) were recruited with active parental consent from three middle schools. Adolescents completed self-report questionnaires Regarding demo graphics, maladaptive behaviors, emotion regulation, and friendship quality, and GPA data were collected from the school. Regression analyses found that GPA was negatively related to externalizing symptoms. Girls with poor friendship communication report significantly higher maladaptive behaviors. This relation was more pronounced for girls with high GPAs, as predicted. Results support the theory that intelligent female adolescents are more reactive under adverse circumstances. Future efforts should follow students through middle school into high school to evaluate whether friendships remain important to adjustment, hold for boys as well as girls, and have implications for relationship interventions.
ContributorsGonzales, Ashlyn Carol (Author) / Luthar, Suniya (Thesis director) / Davis, Mary (Committee member) / Infurna, Frank (Committee member) / Department of Psychology (Contributor) / Sanford School of Social and Family Dynamics (Contributor) / Barrett, The Honors College (Contributor)
Created2017-12
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Description
Resilience is defined as an individual's ability to cope or "bounce back" after experiencing stressful life events (Rew et al., 2001). Survivors of trauma who express high levels of resilience are more likely to experience positive future life outcomes than equally troubled peers with lower resilience scores. It is possible

Resilience is defined as an individual's ability to cope or "bounce back" after experiencing stressful life events (Rew et al., 2001). Survivors of trauma who express high levels of resilience are more likely to experience positive future life outcomes than equally troubled peers with lower resilience scores. It is possible to increase resilience by targeting several core factors: (1) personal competence, (2) sense of belonging, (3) sense of optimism (Lee et al., 2009). I developed an eight-week creative writing curriculum to boost these three core factors in the hopes of both increasing resilience in homeless youth while also introducing creating writing as an effective coping strategy. Each one-hour session included free-form writing exercises, mindfulness practices, writing workshops, and group presentations. Prompts and activities were carefully developed to encourage resilience-building in a group of homeless children and adolescents of ages seven to fourteen at Homeward Bound in Phoenix. With sample writing works and facilitator feedback, this curriculum was designed to be exceptionally easy and cost effective for future implementation. I hope that other organizations in the future will consider implementing this program to help build resilience in youth who have experienced childhood trauma.
ContributorsPopeski, Cara (Author) / Popova, Laura (Thesis director) / Cavanaugh Toft, Carolyn (Committee member) / Pickhart, Kalani (Committee member) / Department of Psychology (Contributor) / Barrett, The Honors College (Contributor)
Created2017-05
Description

The ERK1/2 cell signaling pathway is highly conserved and a prominent regulator of processes like cell proliferation, differentiation, and survival. During nervous system development, the ERK1/2 cascade is activated by the binding of growth factors to receptor tyrosine kinases, leading to the sequential phosphorylation of intracellular protein kinases in the

The ERK1/2 cell signaling pathway is highly conserved and a prominent regulator of processes like cell proliferation, differentiation, and survival. During nervous system development, the ERK1/2 cascade is activated by the binding of growth factors to receptor tyrosine kinases, leading to the sequential phosphorylation of intracellular protein kinases in the pathway and eventually ERK1 and ERK2, the effectors of the pathway. Well-defined germline mutations resulting in hyperactive ERK1/2 signaling have been implicated in a group of neurodevelopmental disorders called RASopathies. RASopathic individuals often display features such as developmental delay, intellectual disability, cardio-facial abnormalities, and motor deficits. In addition, loss-of-function in ERK1/2 can lead to neurodevelopmental disorders such as autism spectrum disorder (ASD) and intellectual disability. To better understand the pathology of these neurodevelopmental disorders, the role of ERK1/2 must be examined during the development of specific neuronal and glial subtypes. In this study, we bred transgenic mice with conditional deletion of ERK1/2 in cholinergic neuronal populations to investigate whether ERK1/2 mediates the survival or activity of basal forebrain and striatal cholinergic neurons during postnatal development. By postnatal day 10, we found that ERK1/2 did not seem to mediate cholinergic neuron number within the basal forebrain or striatum. In addition, we showed that expression of FosB, a neuronal activity-dependent transcription factor and target of ERK1/2, was not yet observed in cholinergic neurons within either of these anatomical regions by P10. Finally, our preliminary data suggested that FosB expression within layer IV of the somatosensory cortex, a target domain for basal forebrain cholinergic projections, also did not appear to be mediated by ERK1/2 signaling. However, since cholinergic neuron development is not yet complete by P10, future work should explore whether ERK1/2 plays any role in the long-term survival and function of basal forebrain and striatal cholinergic neurons in adulthood. This will hopefully provide more insight into the pathology of neurodevelopmental disorders and inform future therapeutic strategies.

ContributorsBalasubramanian, Kavya (Author) / Newbern, Jason (Thesis director) / Velazquez, Ramon (Committee member) / Rees, Katherina (Committee member) / Barrett, The Honors College (Contributor) / Department of Psychology (Contributor)
Created2023-05
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Description
The goal of this thesis was to create a theory of change for an annual Multicultural Arts Camp (MAC) that offers youth with trauma histories opportunities to cultivate protective factors associated with resilience. MAC is designed to promote four primary protective outcomes among its participants: (1) safety, (2) self-expression, (3)

The goal of this thesis was to create a theory of change for an annual Multicultural Arts Camp (MAC) that offers youth with trauma histories opportunities to cultivate protective factors associated with resilience. MAC is designed to promote four primary protective outcomes among its participants: (1) safety, (2) self-expression, (3) skill-building and (4) self-efficacy through exploration of various multicultural art forms and connecting with caring adults. The theory of change was informed by my observations during my experience as a MAC volunteer and my review of academic literature to better define and understand how various factors involved in the MAC program are linked to resilience processes. Arts programming can provide opportunities for youth who have experienced trauma to feel safe enough to engage in self-expression and build corresponding skills that promote feelings of self-efficacy. Building these protective factors thereby strengthens children’s capacity for resilience. Accordingly, the theory of change articulates program activities and processes that promote these outcomes among participating youth. Program directors may draw on the theory of change for strategic planning and evaluation efforts assessing the program’s processes and corresponding impact.
ContributorsJanss, Alena Lilia (Author) / Sechler, Casey (Thesis director) / Foster, Stacie (Committee member) / Department of Psychology (Contributor) / Sanford School of Social and Family Dynamics (Contributor) / Barrett, The Honors College (Contributor)
Created2020-05
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Description
Attention-deficit/hyperactivity disorder (ADHD) is a common developmental disorder characterized by symptoms of impulsivity, inattention, and hyperactivity that interfere with development. Given the lasting academic and social deficits associated with ADHD symptoms, it is critical to study the risk factors of this disorder and possible factors that could protect against its

Attention-deficit/hyperactivity disorder (ADHD) is a common developmental disorder characterized by symptoms of impulsivity, inattention, and hyperactivity that interfere with development. Given the lasting academic and social deficits associated with ADHD symptoms, it is critical to study the risk factors of this disorder and possible factors that could protect against its development. Therefore, the current study investigated the potential role of social support from parents, siblings, teachers, and peers as promotive and protective factors against the development of ADHD symptoms for children at familial risk of developing ADHD symptoms. Participants included 903 twins (30.5% monozygotic twins, 35.9% same-sex dizygotic twins, 31.7% opposite-sex dizygotic twins) from the longitudinal Arizona Twin Project. Children (51.6% female) were assessed for social support and ADHD symptoms at age 8 (M = 8.42, SD = 0.68) and for ADHD symptoms at age 9 (M = 9.71, SD = 0.93). Children’s familial risk for developing ADHD symptoms was assessed as a function of their cotwin’s symptom status at age 8 and the pair’s zygosity. Mixed model regression analyses indicated that familial risk was a robust predictor of ADHD symptoms. Further, peer acceptance was found to operate as a promotive factor against the development of ADHD symptoms, with some evidence for positive parenting as a promotive factor, as well. None of the forms of social support were found to be protective factors for children at familial risk of developing ADHD symptoms. Bivariate twin analyses revealed that peer acceptance and ADHD were related for both genetic and environmental reasons, suggesting that children’s heritable behaviors influence their peer acceptance. Future directions may include examining additional factors as possible moderators of familial risk of developing ADHD symptoms.
ContributorsHawkins, Jessica Kathryn (Author) / Lemery-Chalfant, Kathryn (Thesis director) / Miadich, Samantha (Committee member) / School of Life Sciences (Contributor) / Department of Psychology (Contributor) / Barrett, The Honors College (Contributor)
Created2020-12
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Description

I did a literature review on how childhood trauma causes health issues in the future. Based on the information gathered, I did a clinical proposal for trauma informed care to help address this problem.

ContributorsShanavas, Yuktha (Author) / Infurna, Frank (Thesis director) / Ha, Thao (Committee member) / Barrett, The Honors College (Contributor) / Department of Psychology (Contributor)
Created2022-05
Description
Chronic pain is common among children and can lead to future physical disability and health problems. The Biopsychosocial model of child pain suggests that biological, psychological, and social factors predict pain risk, but most research has focused on biological and psychological factors impacting child pain, and less on social factors.

Chronic pain is common among children and can lead to future physical disability and health problems. The Biopsychosocial model of child pain suggests that biological, psychological, and social factors predict pain risk, but most research has focused on biological and psychological factors impacting child pain, and less on social factors. One social factor is family stress, including parent mental and physical health problems, and parenting and marital stress. The impact of stress, however, may vary depending on the presence of positive family resources, including marital empathy, parental warmth, and interpersonal support. Thus, the current longitudinal study examined links between family stress and increases in child pain during middle childhood and tested whether positive resources acted as a buffer to protect the development of child pain and if low social status acted as an extra stressor to make pain worse. Participants were part of the Arizona Twin Project, an ongoing longitudinal project of twins. At twin age 9, primary caregivers (PCs) reported on different stress, social status, and positive resources measures, and PCs and twins reported on twin bodily pain. At twin age 11, PCs and twins again reported on twin chronic bodily pain. Neither greater family stress nor parent physical health problems predicted increases in child pain over two years, controlling for twin pain at age 9. In tests of moderation, a single significant interaction emerged in a direction opposite of prediction: the relation between family stress and child pain was moderated by social status, such that average and high levels of social status exacerbated the relation between family stress, and child pain at age 11. Although the interaction needs to be replicated, findings suggest that high social status may act as a risk factor for poor child physical health and pain when family stress is high. Future research should further explore whether and how family stress and social status, as well as peer stress and resources, alone and in combination predict health as children age into adolescence.
ContributorsRusy, Isabella (Author) / Davis, Mary (Thesis director) / Corbin, William (Committee member) / Lemery-Chalfant, Kathryn (Committee member) / Barrett, The Honors College (Contributor) / Department of Psychology (Contributor) / School of Criminology and Criminal Justice (Contributor)
Created2023-12