Matching Items (162)
Description
Dysregulated cortisol is a risk factor for poor health outcomes. Children of distressed mothers exhibit dysregulated cortisol, yet it is unclear whether maternal distress predicts cortisol activity in later developmental stages. This longitudinal study examined the prospective relation between maternal distress during late childhood (9–12 years) and adolescence (15–19 years) and cortisol response in offspring in young adulthood (24–28 years). Data were collected from 51 recently divorced mothers and their children across 15 years. Higher maternal distress during late childhood was associated with lower total cortisol independent of levels of maternal distress in adolescence or young adulthood. Maternal distress during adolescence marginally predicted blunted cortisol when distress in childhood was low. Findings suggest that blunted cortisol activity in young adulthood may be a long-term consequence of exposure to maternal distress earlier in development.
ContributorsMahrer, Nicole (Author) / Luecken, Linda (Author) / Wolchik, Sharlene (Author) / Tein, Jenn-Yun (Author) / Sandler, Irwin (Author) / College of Liberal Arts and Sciences (Contributor) / Department of Psychology (Contributor)
Created2014-11-01
Description
Traumatic brain injury (TBI) consists of the primary mechanical forces to the head followed by secondary inflammatory cascades. This inflammatory cascade consists of neuroinflammation characterized by microglial activation as the first line of defense. Another component of secondary inflammation comprises of activation of peripheral immune cells that can infiltrate the compromised blood brain barrier and susceptible organs such as the lungs. Acute inflammatory processes in the lungs include a disruption of the epithelial barriers allowing infiltration of neutrophils, and edema build up in the alveoli. This is known as acute lung injury (ALI) and it dampens respiratory function in approximately 20-25% of TBI patients necessitating an intervention. Remote ischemic conditioning (RIC) is an intervention consisting of repeated intervals of cessation and reperfusion of blood flow to a distal limb and has treated ALI, myocardial infarction, and neurological injury. TBI was hypothesized to induce ALI through degradation of alveolar-capillary membrane and infiltration of peripheral leukocytes. Furthermore, RIC was hypothesized to protect the integrity of the alveolar-capillary membrane, reduce infiltration of peripheral immune cells, and reduce microglial activation in the brain through myokine recruitment. Male CD1 mice were subject to either midline fluid percussion or sham injury and further randomized into 4 groups: sham, sham RIC, TBI, TBI RIC. RIC was administered on proximal thigh for 4x5 minutes, with 5-minute reperfusion one hour prior to TBI. One-hour post-injury, brain, lung, BAL fluid, and blood were collected. Lung histopathology showed RIC reduced hydrostatic edema in the alveoli by protecting the alveolar capillary membrane. BAL findings revealed TBI mice had increased neutrophil counts, RIC lowered neutrophil counts. In the brain, RIC increased cortex microglial endpoints were observed with no other significant differences in microglial morphology as well as plasma myokine levels across all sham, sham RIC, TBI, and TBI RIC animals. While underlying mechanisms still have to be further studied, this current study provides evidence that RIC can be used as a therapeutic intervention to ameliorate TBI-induce ALI.
ContributorsChristie, Immaculate (Author) / Newbern, Jason (Thesis director) / Lifshitz, Jonathan (Committee member) / Saber, Maha (Committee member) / School of Life Sciences (Contributor, Contributor) / Barrett, The Honors College (Contributor)
Created2020-05
Description
Immediate early genes (IEGs) are rapidly activated in response to an environmental stimulus, and most code for transcription factors that mediate processes of synaptic plasticity, learning, and memory. EGR3, an immediate early gene transcription factor, is a mediator of biological processes that are disrupted in patients with schizophrenia (SCZ). A microarray experiment conducted by our lab revealed that Egr3 also regulates genes involved in DNA damage response. A recent study revealed that physiological neuronal activity results in the formation of DNA double-stranded breaks (DSBs) in the promoters of IEGs. Additionally, they showed that these DSBs are essential for inducing the expression of IEGs, and failure to repair these DSBs results in the persistent expression of IEGs. We hypothesize that Egr3 plays a role in repairing activity- induced DNA DSBs, and mice lacking Egr3 should have an abnormal accumulation of these DSBs. Before proceeding with that experiment, we conducted a preliminary investigation to determine if electroconvulsive stimulation (ECS) is a reliable method of inducing activity- dependent DNA damage, and to measure this DNA damage in three subregions of the hippocampus: CA1, CA3, and dentate gyrus (DG). We asked the question, are levels of DNA DSBs different between these hippocampal subregions in animals at baseline and following electroconvulsive stimulation (ECS)? To answer this question, we quantified γ-H2AX, a biomarker of DNA DSBs, in the hippocampal subregions of wildtype mice. Due to technical errors and small sample size, we were unable to substantiate our preliminary findings. Despite these shortcomings, our experimental design can be modified in future studies that investigate the role of Egr3 in activity-induced DNA damage repair.
ContributorsKhoshaba, Rami Samuel (Author) / Newbern, Jason (Thesis director) / Gallitano, Amelia (Committee member) / Marballi, Ketan (Committee member) / School of Molecular Sciences (Contributor) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2020-05
Description
Damage to DNA can affect the genes it encodes; if this damage is not repaired, abnormal proteins may be produced and cellular functions may be disturbed. DNA damage has been implicated in the initiation and progression of a variety of diseases. Conversely, DNA damage has also been discovered to contribute to beneficial biological processes. Madabhushi and colleagues (2015) determined that activity-dependent DNA double strand breaks (DSBs) in the promoter region of immediate early genes (IEGs) induced their expression. EGR3 is an IEG transcription factor which regulates the expression of growth factors and synaptic plasticity-associated genes. In a previously conducted microarray experiment, it was revealed that EGR3 regulates the expression of genes associated with DNA repair such as Cenpa and Nr4a2. These findings inspired us to investigate if EGR3 affects DNA repair in vivo. Before conducting this experiment, we sought to standardize and optimize a method of inducing DNA damage in the hippocampus. Electroconvulsive stimulation (ECS) is utilized to induce neuronal activity. Since neuronal activity leads to the formation of DNA DSBs, we theorized that ECS could be used to induce DNA DSBs in the hippocampus. We predicted that mice that receive ECS would have more DNA DSBs than those that receive the sham treatment. Gamma H2AX, a biomarker for DNA damage, was utilized to quantify DNA DSBs. Gamma H2AX expression in the dentate gyrus, CA1 and CA3 regions of the hippocampus was compared between mice that received the sham treatment and mice that received ECS. Mice that received ECS were sacrificed either 1 or 2 hours post-administration, constituting treatment conditions of 1 hr post-ECS and 2 hrs post-ECS. Our results suggest that ECS has a statistically significant effect exclusively in the CA1 region of the hippocampus. However, our analyses may have been limited due to sample size. A power analysis was conducted, and the results suggest that a sample size of n=4 mice will be sufficient to detect significant differences across treatments in all three regions of the hippocampus. Ultimately, future studies with an increased sample size will need to be conducted to conclusively assess the use of ECS to induce DNA damage within the hippocampus.
ContributorsAden, Aisha Abubakar (Author) / Newbern, Jason (Thesis director) / Gallitano, Amelia (Thesis director) / Marballi, Ketan (Committee member) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2020-05
Description
In the study of the human brain’s ability to multitask, there are two perspectives: concurrent multitasking (performing multiple tasks simultaneously) and sequential multitasking (switching between tasks). The goal of this study is to investigate the human brain’s ability to “multitask” with multiple demanding stimuli of approximately equal concentration, from an electrophysiological perspective different than that of stimuli which don’t require full attention or exhibit impulsive multitasking responses. This study investigates the P3 component which has been experimentally proven to be associated with mental workload through information processing and cognitive function in visual and auditory tasks, where in the multitasking domain the greater attention elicited, the larger P3 waves are produced. This experiment compares the amplitude of the P3 component of individual stimulus presentation to that of multitasking trials, taking note of the brain workload. This study questions if the average wave amplitude in a multitasking ERP experiment will be the same as the grand average when performing the two tasks individually with respect to the P3 component. The hypothesis is that the P3 amplitude will be smaller in the multitasking trial than in the individual stimulus presentation, indicating that the brain is not actually concentrating on both tasks at once (sequential multitasking instead of concurrent) and that the brain is not focusing on each stimulus to the same degree when it was presented individually. Twenty undergraduate students at Barrett, the Honors College at Arizona State University (10 males and 10 females, with a mean age of 18.75 years, SD= 1.517) right handed, with normal or corrected visual acuity, English as first language, and no evidence of neurological compromise participated in the study. The experiment results revealed that one- hundred percent of participants undergo sequential multitasking in the presence of two demanding stimuli in the electrophysiological data, behavioral data, and subjective data. In this particular study, these findings indicate that the presence of additional demanding stimuli causes the workload of the brain to decrease as attention deviates in a bottleneck process to the multiple requisitions for focus, indicated by a reduced P3 voltage amplitude with the multitasking stimuli when compared to the independent. This study illustrates the feasible replication of P3 cognitive workload results for demanding stimuli, not only impulsive-response experiments, to suggest the brain’s tendency to undergo sequential multitasking when faced with multiple demanding stimuli. In brief, this study demonstrates that when higher cognitive processing is required to interpret and respond to the stimuli, the human brain results to sequential multitasking (task- switching, not concurrent multitasking) in the face of more challenging problems with each stimulus requiring a higher level of focus, workload, and attention.
ContributorsNeill, Ryan (Author) / Brewer, Gene (Thesis director) / Peter, Beate (Committee member) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2019-05
Description
Music and emotions have been studied frequently in the past as well as music and memory. However, these three items don’t have as much research grouped together. Further, this research does not also encompass culture. In my research, the aim was to examine the relationship between music, memory, emotion, and culture of gender. The hypothesis was that women had more emotions linked to music than men. We gave 416 students an animal fluency task, a letter fluency task, six cultural fluency tasks, and a cultural identity survey. We used a t-test and created a graph to analyze my data. After administering my tasks, we found that women had recalled more adjectives linked to music than men. However, there was not a statistically significant difference between the number of adjectives with emotional valence between men and women, indicating that there was no relationship between gender and emotion in regards to music. The limitations on this study included the descriptions on how to complete the task, the cultural norms of the participants, and the disparity between the number of female and male participants. In a future study, it is necessary to be more specific in what is desired from the participants and to pay close attention to shifting gender norms. Further, we would also like to see how the results from future research can impact music therapy for memory-related mood disorders.
ContributorsLevin, Allison (Author) / Brewer, Gene (Thesis director) / Cohen, Adam (Committee member) / Sanford School of Social and Family Dynamics (Contributor) / Department of Psychology (Contributor) / College of Integrative Sciences and Arts (Contributor) / School of International Letters and Cultures (Contributor) / Barrett, The Honors College (Contributor)
Created2019-05
Description
Traumatic brain injury (TBI) is a major cause of disability, with approximately 1.7 million incidents reported annually. Following a TBI, patients are likely to sustain sensorimotor and cognitive impairments and are at an increased risk of developing neurodegenerative diseases later in life. Despite this, robust therapies that treat TBI neuropathology are not available in the clinic. One emerging therapeutic approach is to target epigenetic mediators that modulate a variety of molecular regulatory events acutely following injury. Specifically, previous studies demonstrated that histone deacetylase inhibitor (HDACi) administration following TBI reduced inflammation, enhanced functional outcomes, and was neuroprotective. Here, we evaluated a novel quisinostat-loaded PLA-PEG nanoparticle (QNP) therapy in treating TBI as modeled by a controlled cortical impact. We evaluated initial pharmacodynamics within the injured cortex via histone acetylation levels following QNP treatment. We observed that QNP administration acutely following injury increased histone acetylation specifically within the injury penumbra, as detected by Western blot analysis. Given this effect, we evaluated QNP therapeutic efficacy. We observed that QNP treatment dampened motor deficits as measured by increased rotarod latency to fall relative to blank nanoparticle- and saline-treated controls. Additionally, open field results show that QNP treatment altered locomotion following injury. These results suggest that HDACi therapies are a beneficial therapeutic strategy following neural injury and demonstrate the utility for nanoparticle formulations as a mode for HDACi delivery following TBI.
ContributorsMousa, Gergey (Author) / Stabenfeldt, Sarah (Thesis director) / Newbern, Jason (Committee member) / Sirianni, Rachael (Committee member) / School of Life Sciences (Contributor) / Harrington Bioengineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2019-05
Description
The highly conserved Notch signaling pathway regulates cell-cell communication pathways, cell fate, cell determination, cell death, embryonic development, and adult tissue pathways in metazoans. The Notch receptors and ligands that bind to Notch are single pass, transmembrane proteins that communicate cell to cell via juxtacrine signaling. There are reports of the divergent function and localization of the Deltalike 3 (Dll3) ligand. In Mus musculus (an eutherin mammal) the DLL3 protein inhibits the Notch signaling pathway and is localized in the Golgi apparatus. In contrast, the DLL3 protein from zebrafish, Danio rerio (a teleost) activates Notch and is located on the cell surface. This study will focus on examining the evolutionary pathway/evolutionary similarities, localization, and function of the A. carolinensis dll3 gene in comparison to other vertebrate species. This is important because there is not much known about the evolutionary divergence of the DLL3 A. carolinensis protein, its function in Notch signaling, and its subcellular localization.
Evolutionary analysis of vertebrate DLL3 protein sequences using phylogenetic trees showed that D. rerio and A. carolinensis are more evolutionarily similar in comparison to M. musculus suggesting that they may have similar intracellular localization. However, immunofluorescence staining experiments showed that the A. carolinensis DLL3 protein co-localized significantly with an endoplasmic reticulum (ER) specific primary antibody. Since this protein is localized in the secretory system, similar to that of M. musculus DLL3, it suggests that its function is to inhibit the Notch signaling pathway. Protein sequence alignments were created that suggested that there is a region in the protein sequences where the lizard and mouse sequence are conserved, while the zebrafish sequence simultaneously varies. This region of the amino acid sequence could be responsible for the difference in localization and function of the protein in these two species.
Evolutionary analysis of vertebrate DLL3 protein sequences using phylogenetic trees showed that D. rerio and A. carolinensis are more evolutionarily similar in comparison to M. musculus suggesting that they may have similar intracellular localization. However, immunofluorescence staining experiments showed that the A. carolinensis DLL3 protein co-localized significantly with an endoplasmic reticulum (ER) specific primary antibody. Since this protein is localized in the secretory system, similar to that of M. musculus DLL3, it suggests that its function is to inhibit the Notch signaling pathway. Protein sequence alignments were created that suggested that there is a region in the protein sequences where the lizard and mouse sequence are conserved, while the zebrafish sequence simultaneously varies. This region of the amino acid sequence could be responsible for the difference in localization and function of the protein in these two species.
ContributorsBoschi, Alexis (Author) / Wilson-Rawls, Jeanne (Thesis director) / Newbern, Jason (Committee member) / Wilson Sayres, Melissa (Committee member) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2019-05
Description
Cocaine use remains a prevalent problem, yet there are no effective pharmacological treatments against cocaine use disorders. Cocaine is known to affect serotonin neurotransmission in the brain. Previous data has shown the modulatory role of CP 94,253, a serotonin 1B receptor (5-HT1BR) agonist on cocaine self-administration at different periods of the use-abstinence-relapse cycle. CP 94,253 facilitates cocaine self-administration in rats during the use maintenance phase, where rats are receiving daily intake of cocaine, yet attenuates it after a period of abstinence, when drug delivery is discontinued and rats are placed in home cages. Here we study the therapeutic potential of 5-HT1BR agonist pre-treatment on cocaine self-administration during these different time periods. Male and free-cycling female rats were trained to lever-press for cocaine (0.75 mg/kg i.v.) or sucrose pellets, until they met stable performance for total number of infusions on a fixed ratio 5 schedule of reinforcement. Rats were then tested with either the FDA-approved but less selective 5-HT1BR agonist zolmitriptan (3, 5.6, and 10 mg/kg s.c.; in descending order) prior to a period of abstinence or the more selective 5-HT1BR agonist CP 94,253 (5.6 mg/kg s.c.) after a period of prolonged abstinence and relapse (i.e. resumption of daily cocaine self-administration after a period of abstinence). Each session ran for 2 hours during which the training dose was available for the 1st hour and a low dose of cocaine (0.075 mg/kg i.v.) for the 2nd hour. Zolmitriptan was found to attenuate cocaine self-administration measures at a dose of 3 and 5.6 mg/kg when testing at the low dose of cocaine and at all three doses (3, 5.6, and 10 mg/kg) when testing at the training dose of cocaine. Zolmitriptan at the doses effective at attenuating cocaine intake did not alter sucrose self-administration. CP 94,253 (5.6 mg/kg s.c.) was found to have significant attenuative effects on self-administration measures both after a period of prolonged abstinence and after a period of relapse. Overall, these experiments showed that zolmitriptan decreased cocaine reinforcement without altering sucrose reinforcement as well as that CP 94,253 attenuates cocaine intake even after a period of relapse. These findings support the therapeutic potential of 5-HT1BR agonists as pharmacological treatments for cocaine use disorders.
ContributorsLe, Tien (Author) / Neisewander, Janet (Thesis director) / Newbern, Jason (Committee member) / Garcia, Raul (Committee member) / Chemical Engineering Program (Contributor, Contributor) / School of International Letters and Cultures (Contributor) / Barrett, The Honors College (Contributor)
Created2020-05
Description
The first step in providing adequate prevention of children’s behavior problems is identifying possible predictors. There is an established relation between parenting style and behaviors and children’s future outcomes, including risk of externalizing behavior problems, but the mechanisms that may explain this relation are unclear. The current study investigated whether child executive functioning plays a mediating role between parenting style and externalizing behavior problems. I hypothesized that parenting style, specifically harsh authoritarian parenting, would predict a decrease in child executive performance, then leading to increased child behavior problems. Additionally, sex differences within this model were examined. Parenting styles and child externalizing behavior problems were measured through mother’s self-report within a sample of 322 low-income, Mexican-American mother child dyads in the Phoenix metropolitan area. A mediation model was performed, including relevant covariates, to test for significance of the mediated pathway. The results of the current study indicated that authoritarian parenting style significantly predicted greater externalizing behavior problems in the sample, but only for girls. Interestingly, it was also found that the addition of biological siblings predicted less behavior problems, again only for girls. These results promote understanding of the influences on behavior problems in children that can escalate to delinquency and criminal behavior. This information is critical for the development and improvement of strategic interventions.
ContributorsPerry, Beth Madison (Author) / Luecken, Linda (Thesis director) / Presson, Clark (Committee member) / van Huisstede, Lauren (Committee member) / School of Life Sciences (Contributor, Contributor) / Department of Psychology (Contributor) / Barrett, The Honors College (Contributor)
Created2020-05