Matching Items (6)
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- All Subjects: Resilience
- Creators: Infurna, Frank
Description
Chronic stress results in functional and structural changes to the hippocampus. Decades of research has led to insights into the mechanisms underlying the chronic stress-induced deficits in hippocampal-mediated cognition and reduction of dendritic complexity of hippocampal neurons. Recently, a considerable focus of chronic stress research has investigated the mechanisms behind the improvements in hippocampal mediated cognition when chronic stress ends and a post-stress rest period is given. Consequently, the goal of this dissertation is to uncover the mechanisms that allow for spatial ability to improve in the aftermath of chronic stress. In chapter 2, the protein brain derived neurotrophic factor (BDNF) was investigated as a mechanism that allows for spatial ability to show improvements following the end of chronic stress. It was found that decreasing the expression of BDNF in the hippocampus prevented spatial memory improvements following a post-stress rest period. Chapter 3 was performed to determine whether hippocampal CA3 apical dendritic complexity requires BDNF to show improvements following a post-stress rest period, and whether a receptor for BDNF, TrkB, mediates the improvements of spatial ability and dendritic complexity in a temporal manner, i.e. during the rest period only. These experiments showed that decreased hippocampal BDNF expression prevented improvements in dendritic complexity, and administration of a TrkB antagonist during the rest period also prevented the improvements in spatial ability and dendritic complexity. In chapter 4, the role of the GABAergic system on spatial ability following chronic stress and a post-stress rest period was investigated. Following chronic stress, it was found that male rats showed impairments on the acquisition phase of the RAWM and this correlated with limbic glutamic acid decarboxylase, a marker for GABA. In chapter 5, a transgenic mouse that expresses a permanent marker on all GABAergic interneurons was used to assess the effects of chronic stress and a post-stress rest period on hippocampal GABAergic neurons. While no changes were found on the total number of GABAergic interneurons, specific subtypes of GABAergic interneurons were affected by stressor manipulations. Collectively, these studies reveal some mechanisms behind the plasticity seen in the hippocampus in response to a post-stress rest period.
ContributorsOrtiz, J. Bryce (Author) / Conrad, Cheryl D. (Thesis advisor) / Newbern, Jason M. (Committee member) / Orchinik, Miles (Committee member) / Sanabria, Federico (Committee member) / Arizona State University (Publisher)
Created2018
Description
Cognitive reappraisal, or redefining the meaning of a stressful circumstance, is useful in regulating emotional responses to acute stressors and may be mobilized to up- or down- regulate the stressors’ emotional salience. A conceptually-related but more targeted emotion regulation strategy to that offered by cognitive reappraisal, termed positive cognitive shift, was examined in the current study. Positive cognitive shift (“PCS”) is defined as a point of cognitive transformation during a chronic, stressful situation that alters the meaning and emotional salience of the situation for the individual. Key aspects of the PCS that differentiate it from the broader reappraisal construct are that it 1) is relevant to responses to chronic (versus acute) aversive events, 2) is deployed when there is a mismatch between coping and stressors, and 3) involves insight together with redefinition in meaning of the situation generating stress. The current study used qualitative and quantitative analyses to 1) examine whether PCS is an observable, reliable, and valid experience in response to a stressful event that occurred in the past year, and 2) test whether PCS moderates the relations between the number of past-year stressful life circumstances and subsequent emotional well-being and functional health. A community sample of 175 middle-aged individuals were interviewed regarded a past chronic stressor and completed questionnaires regarding number of past year stressors and health outcomes. Theory-based coding of interviews was conducted to derive reliable scores for PCS, and findings indicated that PCS was evident in 37.7 % of participant responses. Furthermore, PCS scores were related positively to openness, personal growth from one’s most difficult lifetime event, and affect intensity-calm, in line with predictions. Also in line with prediction, PCS moderated the relations between number of past-year life events and health outcomes, such that the deleterious relations between past year stressful events and cognitive functioning, wellbeing, positive affect, and negative affect were weaker among individuals higher versus lower in PCS. Of note, PCS moderation effects diminished as the number of stressful events increased.
ContributorsRivers, Crystal (Author) / Davis, Mary (Thesis advisor) / Luecken, Linda (Committee member) / Infurna, Frank (Committee member) / Robinson Kurpius, Sharon (Committee member) / Arizona State University (Publisher)
Created2018
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 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
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 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
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) 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
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