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- Creators: School of Life Sciences
Description
Monoamine neurotransmitters (e.g., serotonin, norepinephrine, and dopamine) are powerful modulators of mood and cognitive function in health and disease. We have been investigating the modulation of monoamine clearance in select brain regions via organic cation transporters (OCTs), a family of nonselective monoamine transporters. OCTs are thought to complement the actions of selective monoamine transporters in the brain by helping to clear monoamines from the extracellular space; thus, assisting to terminate the monoamine signal. Of particular interest, stress hormones (corticosterone; CORT) inhibit OCT3-mediated transport of monoamine, to putatively lead to prolonged monoamine signaling. It has been demonstrated that stress levels of CORT block OCT3 transport in the rat hypothalamus, an effect that likely underlies the rapid, stress-induced increase in local monoamines. We examined the effect of chronic variable stress (CVS) on the development of mood disorders and OCT3 expression in limbic and hypothalamic regions of the rat brain. Animals subjected to CVS (14-days with random stressor exposure two times/day) showed reduced body weight gain, indicating that CVS was perceived as stressful. However, behavioral tests of anxiety and depressive-like behaviors in rats showed no group differences. Although there were no behavioral effects of stress, molecular analysis revealed that there were stress-related changes in OCT3 protein expression. In situ hybridization data confirmed that OCT3 mRNA is expressed in the hippocampus, amygdala, and hypothalamus. Analysis of Western blot data by two-way ANOVA revealed a significant treatment effect on OCT3 protein levels, with a significant decrease in OCT3 protein in the amygdala and hippocampus in CVS rats, compared to controls. These data suggest an important role for CORT sensitive OCT3 in the reduction of monoamine clearance during stress.
ContributorsBoyll, Piper Savannah (Author) / Orchinik, Miles (Thesis director) / Conrad, Cheryl (Committee member) / Talboom, Joshua (Committee member) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
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
ABSTRACT
Environmental and genetic factors influence schizophrenia risk. Individuals who have direct family members with schizophrenia have a much higher incidence. Also, acute stress or life crisis may precede the onset of the disease. This study aims to understand the effects of environment on genes related to schizophrenia risk. It investigates the impact of sleep deprivation as an acute environmental stressor on the expression of Htr2a in mice, a gene that codes for the serotonin 2A receptor (5-HT2AR). HTR2A is associated with schizophrenia risk through genetic association studies and expression is decreased in post-mortem studies of patients with the disease. Furthermore, sleep deprivation as a stressor in human trials has been shown to increase the binding capacity of 5-HT2AR. We hypothesize that sleep deprivation will increase the number of cells expressing Htr2a in the mouse anterior prefrontal cortex when compared to controls. Sleep deprived that mice express EGFP under control of the Htr2a promoter displayed anteroposterior gradients of expression across sagittal sections, with concentrations seen most densely within the prefrontal cortex as well as the anterior pretectal nucleus, thalamic nucleus, as well as the cingulate gyrus. Htr2a-EGFP expression was most densely visualized in cortical layer V and VI pyramidal neurons within the lateral prefrontal cortex of coronal sections. Furthermore, the medial prefrontal cortex contained significantly cells expressing Htr2a¬-EGFP than the lateral prefrontal cortex. Ultimately, the hypothesis was not supported and sleep deprivation did not result in more ¬Htr2a-EGFP expressing cells compared to basal levels. However, expressing cells appeared visibly brighter in sleep-deprived animals when compared to controls, indicating that the amount of intracellular Htr2a-GFP expression may be higher. This study provides strong visual representations of expression gradients following sleep deprivation as an acute stressor and paves the way for future studies regarding 5H-T2AR’s role in schizophrenia.
Environmental and genetic factors influence schizophrenia risk. Individuals who have direct family members with schizophrenia have a much higher incidence. Also, acute stress or life crisis may precede the onset of the disease. This study aims to understand the effects of environment on genes related to schizophrenia risk. It investigates the impact of sleep deprivation as an acute environmental stressor on the expression of Htr2a in mice, a gene that codes for the serotonin 2A receptor (5-HT2AR). HTR2A is associated with schizophrenia risk through genetic association studies and expression is decreased in post-mortem studies of patients with the disease. Furthermore, sleep deprivation as a stressor in human trials has been shown to increase the binding capacity of 5-HT2AR. We hypothesize that sleep deprivation will increase the number of cells expressing Htr2a in the mouse anterior prefrontal cortex when compared to controls. Sleep deprived that mice express EGFP under control of the Htr2a promoter displayed anteroposterior gradients of expression across sagittal sections, with concentrations seen most densely within the prefrontal cortex as well as the anterior pretectal nucleus, thalamic nucleus, as well as the cingulate gyrus. Htr2a-EGFP expression was most densely visualized in cortical layer V and VI pyramidal neurons within the lateral prefrontal cortex of coronal sections. Furthermore, the medial prefrontal cortex contained significantly cells expressing Htr2a¬-EGFP than the lateral prefrontal cortex. Ultimately, the hypothesis was not supported and sleep deprivation did not result in more ¬Htr2a-EGFP expressing cells compared to basal levels. However, expressing cells appeared visibly brighter in sleep-deprived animals when compared to controls, indicating that the amount of intracellular Htr2a-GFP expression may be higher. This study provides strong visual representations of expression gradients following sleep deprivation as an acute stressor and paves the way for future studies regarding 5H-T2AR’s role in schizophrenia.
ContributorsSchmitz, Kirk Andrew (Author) / Gallitano, Amelia (Thesis director) / Stout, Valerie (Committee member) / Maple, Amanda (Committee member) / Barrett, The Honors College (Contributor) / School of Life Sciences (Contributor)
Created2015-05
Description
The world of podcasting has exploded in popularity in recent years. This medium is being used in education as well as in the public sector to share ideas, news, and stories. This paper reviews the research behind podcast success as a news form and in the educational sector and the implications of these findings for the future. Podcast listeners tend to listen to podcasts for entertainment and, notably, to diversify their time while completing other tasks. New ways to directly stream media from portable devices and advances in the internet have helped bolster the popularity of this media form. Podcasting proved to be successful in higher education as students tended to perform better when given access to podcasts. However, they were only successful when using podcasts as classroom adjuncts. This implies that educational podcasts must be produced differently than ones intended for the public. By reviewing the neuroscience behind language, emotion and memory, it was found that narrative formats that also evoked emotions had a positive ability in enhancing the listeners learning and memory. Keeping this in mind, the developed podcast aimed to bridge educational material to the general public by utilizing narrative as a vessel in which to deliver complex information about medicine, science and neuroscience. The accessibility and virtually non-existent barriers to the podcasting world offer a breadth of knowledge and opinions that have numerous factors of social influence. The impact of podcasting on the modern world deserves more research in sociology and psychology as it continues to grow in popularity.
ContributorsCharbel, Milad (Author) / Sirven, Joseph (Thesis director) / Reddy, Swapna (Committee member) / School of Life Sciences (Contributor, Contributor) / Barrett, The Honors College (Contributor)
Created2019-05
Description
Egr3 is an immediate early gene transcription factor that shows genetic association with schizophrenia, and is found in decreased levels in the brains of schizophrenia patients. Schizophrenia patients also exhibit cognitive and memory deficits, both of which Egr3 has been shown to play a crucial role in. Additionally, high levels of DNA damage are found in the brains of schizophrenia patients. A recent study has shown that DNA damage occurs as a result of normal physiological activity in neurons and is required for induction of gene expression of a subset of early response genes. Also, failure to repair this damage can lead to gene expression in a constitutive switched on state. Egr3 knockout (Egr3-/-) mice show deficits in hippocampal synaptic plasticity and memory. We were interested in characterizing downstream targets of EGR3 in the hippocampus. To determine these targets, electroconvulsive seizure (ECS) was carried out in Egr3 -/- versus wild type (WT) mice, and a microarray study was first done in our lab. ECS maximally stimulates Egr3 expression and we hypothesized that there would be gene targets that are differentially expressed between Egr3 -/- and WT mice that had been subjected to ECS. Two separate analyses of the microarray yielded 65 common genes that were determined as being differentially expressed between WT and Egr3 -/- mice after ECS. Further Ingenuity Pathway Analysis of these 65 genes indicated the Gadd45 signaling pathway to be the top canonical pathway, with the top four pathways all being associated with DNA damage or DNA repair. A literature survey was conducted for these 65 genes and their associated pathways, and 12 of the 65 genes were found to be involved in DNA damage response and/or DNA repair. Validation of differential expression was then conducted for each of the 12 genes, in both the original male cohort used for microarray studies and an additional female cohort of mice. 7 of these genes validated through quantitative real time PCR (qRT-PCR) in the original male cohort used for the microarray study, and 4 validated in both the original male cohort and an independent female cohort. Bioinformatics analysis yielded predicted EGR3 binding sites in promoters of these 12 genes, validating their role as potential transcription targets of EGR3. These data reveal EGR3 to be a novel regulator of DNA repair. Further studies will be needed to characterize the role of Egr3 in repairing DNA damage.
ContributorsBarkatullah, Arhem Fatima (Author) / Newbern, Jason (Thesis director) / Gallitano, Amelia (Committee member) / Marballi, Ketan (Committee member) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
Description
The goal of my study is to test the overarching hypothesis that art therapy is effective because it targets emotional dysregulation that often accompanies significant health stressors. By reducing the salience of illness-related stressors, art therapy may improve overall mood and recovery, particularly in patients with cancer. After consulting the primary literature and review papers to develop psychological and neural mechanisms at work in art therapy, I created a hypothetical experimental procedure to test these hypotheses to explain why art therapy is helpful to patients with chronic illness. Studies found that art therapy stimulates activity of multiple brain regions involved in memory retrieval and the arousal of emotions. I hypothesize that patients with chronic illness have a reduced capacity for emotion regulation, or difficulty recognizing, expressing or altering illness-related emotions (Gross & Barrett, 2011). Further I hypothesize that art therapy improves mood and therapeutic outcomes by acting on the emotion-processing regions of the limbic system, and thereby facilitating the healthy expression of emotion, emotional processing, and reappraisal. More mechanistically, I propose art therapy reduces the perception or salience of stressors by reducing amygdala activity leading to decreased activation of the hypothalamic-pituitary-adrenal (HPA) axis. The art therapy literature and my hypothesis about its mechanisms of action became the basis of my proposed study. To assess the effectiveness of art therapy in alleviating symptoms of chronic disease, I am specifically targeting patients with cancer who exhibit a lack of emotional regulation. Saliva is collected 3 times a week on the day of intervention: morning after waking, afternoon, and evening. Stress levels are tested using one-hour art therapy sessions over the course of 3 months. The Perceived Stress Scale (PSS) assesses an individual's perceived stress and feelings in past and present situations, for the control and intervention group. To measure improvement in overall mood, 10 one-hour art sessions are performed on patients over 10 weeks. A one-hour discussion analyzing the participants' artwork follows each art session. The Spielberger State-Trait Anxiety Inventory (STAI) assesses overall mood for the intervention and control groups. I created rationale and predictions based on the intended results of each experiment.
ContributorsAluri, Bineetha C. (Author) / Orchinik, Miles (Thesis director) / Davis, Mary (Committee member) / Essary, Alison (Committee member) / School of Life Sciences (Contributor) / School for the Science of Health Care Delivery (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
Description
Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's disease, is a devastating illness that causes the degeneration of both upper and lower motor neurons, leading to eventual muscle atrophy. ALS rapidly progresses into paralysis, with patients typically dying due to respiratory complications within three to five years from the onset of their symptoms. Even after many years of research and drug trials, there is still no cure, and current therapies only succeed in increasing life-span by approximately three months. With such limited options available for patients, there is a pressing need to not only find a cure, but also make new treatments available in order to ameliorate disease symptoms. In a genome-wide association study previously conducted by the Translational Genomics Research Institute (TGen), several single-nucleotide polymorphisms (SNPs) upstream of a novel gene, FLJ10968, were found to significantly alter risk for ALS. This novel gene acquired the name FGGY after publication of the paper. FGGY exhibits altered levels of protein expression throughout ALS disease progression in human subjects, and detectable protein and mRNA expression changes in a mouse model of ALS. We performed co-immunoprecipitation experiments coupled with mass spectrometry in order to determine which proteins are associated with FGGY. Some of these potential binding partners have been linked to RNA regulation, including regulators of the splicesomal complex such as SMN, Gemin, and hnRNP C. To further validate these findings, we have verified co-localization of these proteins with one another. We hypothesize that FGGY plays an important role in ALS pathogenesis, and we will continue to examine its biological function.
ContributorsTerzic, Barbara (Author) / Jensen, Kendall (Thesis director) / Francisco, Wilson (Committee member) / Barrett, The Honors College (Contributor) / School of Mathematical and Statistical Sciences (Contributor) / Department of Chemistry and Biochemistry (Contributor) / School of Life Sciences (Contributor)
Created2014-05
Description
Recent data suggests that olfactory input is important for antennal lobe development in honey bees. Chronic association of a single odor to food resources during crucial stages of development results in delayed antennal lobe development for mature foraging bees. The antennal lobes of these bees instead closely resemble an immature network observed in young, newly emerged bees. Using an odor stimuli variance assay, learning and memory tests can be used to explore how well honey bees discriminate single odors within complex odor mixtures. Here we are validating two different odor mixtures, a Brassica rapa floral blend and a second replicate mixture composed of common molecularly dissimilar odors. Odors in each mixture are either held constant or varied in concentration over 16 conditioning trials. Subsequent memory tests are performed two hours later to observe the ability of bees to distinguish and recognize specific odor components in each mixture. So far in our assay we find high rates of generalization for both odor mixtures. In general, more bees responded to all odors in the replicate treatment group over the Brassica treatment group. Additionally, bees in the Brassica treatment group did not respond to the target odor. More data is being collected to validate this assay. In future studies, I propose to apply this behavioral assay to bees with an altered olfactory developmental in order to see the functional impacts of this chronic odor association treatment.
ContributorsHalby, Rachael (Author) / Smith, Brian (Thesis director) / Jernigan, Christopher (Committee member) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2017-05
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
Aberrant signaling through the canonical RAS/RAF/MEK/ERK (ERK/MAPK) pathway leads to the pathology of a group of neurodevelopmental disorders called RASopathies. RASopathies are caused by germline mutations in the ERK/MAPK pathway and have an incidence of approximately 1:2000 births. The majority of RASopathies stem from mutations that cause gain-of-function in the ERK/MAPK pathway. In this study, we have begun to unravel the roles that GABAergic interneurons play in the pathology of RASopathies. Our data demonstrate that gain-of-function ERK/MAPK signaling expressed in a GABAergic interneuron-specific fashion leads to forebrain hyperexcitability in mutant mice. Further, some GABAergic interneurons experience activated-caspase 3 mediated apoptosis in the embryonic subpallium, leading to a loss of PV-expressing interneurons in the somatosensory cortex. We found that pharmaceutical intervention during embryogenesis using a MEK1 inhibitor may be effective in preventing apoptosis of these neurons. Future work is still needed to understand the mechanism of the death of GABAergic interneurons and to further pursue therapeutic approaches. Taken together, this study suggests potential roles of cortical GABAergic interneurons in ERK/MAPK-linked pathologies and indicates possible approaches to provide therapy for these conditions.
ContributorsShah, Shiv (Author) / Newbern, Jason (Thesis director) / Gipson-Reichardt, Cassandra (Committee member) / School of Life Sciences (Contributor) / Economics Program in CLAS (Contributor) / Barrett, The Honors College (Contributor)
Created2019-05