Interdisciplinary Neuroscience Program electronic theses and dissertations (MU)
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The items in this collection are the theses and dissertations written by students of the Interdisciplinary Neuroscience Program. Some items may be viewed only by members of the University of Missouri System and/or University of Missouri-Columbia. Click on one of the browse buttons above for a complete listing of the works.
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Item Blast-induced mild-traumatic brain injury : identifying molecular biosignatures associated with post-traumatic deficits and disease progression(University of Missouri--Columbia, 2025) Jackson, Marcus N, Jr.; Gu, ZezongBlast-induced mild traumatic brain injury (mTBI) is a critical concern for active-duty military personnel and veterans, leading to both acute and chronic neurological comorbidities that can greatly impact one's life. In recent years, it has become more widely recognized that low-intensity blast (LIB) exposure can cause a unique type of brain injury, differing from direct impact injuries to the head, which are the predominant cause of mTBI in the civilian population. LIB-induced mTBI is most common in military settings, particularly in training scenarios and combat-related operations. However, it was not until 2022 that blast exposure was established as a true cause of TBI, despite cases being tracked back to World War I. Since then, combined research efforts from government and military-funded programs have led to an increased understanding of the impact that LIBs have on brain health and neuropsychiatric function. However, much remains unknown about its pathophysiology and the factors driving chronic symptoms. Our lab addresses this critical gap by studying the behavioral and biochemical changes that occur in mice following LIB (< 50 kPa) exposure in a military-relevant open-field blast (OFB) setting. Our previous work showed that LIB-induced mTBI causes acute and chronic changes in neuronal structure at the nanoscale, alters protein expression related to metabolism as well as synaptic activity and plasticity in eloquent brain regions, induces neuropsychiatric symptoms, impairs cognition, and increases the expression of proteins found in neurodegenerative disorders. This thesis investigated the molecular, structural, and behavioral impact of LIB exposure, with a focus on region-specific molecular alterations, neurovascular unit (NVU) integrity, molecular changes linked to cognitive decline, and tauopathy-driven disease progression. Results showed that (i) exposure to LIB in the prone position induces greater acute changes to brain proteomes, most apparent in the cortex; (ii) LIB damages all structural constituents of the NVU, which may cause leakage of molecules into the plasma; (iii) LIB causes learning deficits post-LIB, which correlate with dysregulated phosphorylation events linked to synaptic dysfunction and cognitive decline; and (iv) the Tau-mTBI interaction drives neuropsychiatric impairments and ADRD progression. We also show that network analyses leveraging of artificial intelligence (AI) algorithms can identify LIB-exposed subjects at high risk for mTBI disease progression toward neurodegenerative disorders, which can transform the TBI screening process. Collectively, this work integrates behavioral, neuropathological, molecular, and computational approaches to advance our understanding of LIB-induced mTBI.Item The utilization of physiological biomarkers for predicting treatment response to pharmaceutical interventions in ADHD and autism(University of Missouri--Columbia, 2025) Appling, Carrina Brooke; Beversdorf, David Q.This dissertation investigates the utility of physiological biomarkers, specifically heart rate variability (HRV), in predicting pharmacologic treatment response in individuals with attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD). Three complementary studies were conducted to examine divergent and convergent thinking in ADHD, Heart rate variability (HRV) use in predict stimulant-induced creative performance, and HRV predicting propranolol response in ASD. In a within-subject study of adults with ADHD, stimulant medications significantly enhanced divergent thinking performance on the Torrance Test of Creative Thinking, while convergent task performance remained unchanged. A follow-up study examined whether baseline HRV predicted the degree of stimulant-induced creativity gains. Although primary time-domain HRV metrics did not significantly predict divergent creativity changes, exploratory analyses identified frequency-domain indices as potential predictors of creative cognition. In a third study of children and young adults with ASD, baseline HRV indices significantly predicted behavioral improvements on the Autism Impact Measure (AIM) in domains of communication and atypical behavior following propranolol treatment, though no significant predictors emerged for clinician-rated anxiety outcomes. Collectively, these findings suggest that HRV may serve as a non-invasive biomarker for characterizing individual differences in autonomic function relevant to treatment responsiveness, offering preliminary support for its role in personalized approaches to pharmacological interventions in ADHD and ASD.Item Using genetically diverse Collaborative Cross mouse strains to model SCN1A-related Dravet Syndrome(University of Missouri--Columbia, 2024) Shakkour, Zaynab; Carney, PaulDravet Syndrome (DS) is classified as a rare neurodevelopmental and epileptic encephalopathy (DEE), characterized by persistent seizures, developmental delays, speech impairments, sleep disruptions, and other comorbidities. Although DS is considered a monogenic disease, it exhibits marked phenotypic heterogeneity that is not fully explained by the causal SCN1A variant. Understanding the genetic basis influencing phenotype severity is challenging through methods like Genome-Wide Association Studies (GWAS) due to limited data on these sporadic variants. Additionally, current DS models fail to capture the full heterogeneity of DS outcomes, restricting their translatable potential. To address these limitations, our study leverages the Collaborative Cross (CC), a panel of genetically diverse recombinant inbred mouse strains. We developed new models of DS by crossing Scn1a+/- 129SvJ male mice with five CC strains and the reference C57BL/6J (B6J). Survival and susceptibility to heat-induced seizures were assessed in a total of 257 F1 mice. Introducing genetic diversity revealed a phenotypic spectrum extending beyond the phenotypes characterized previously. Multivariate analysis provided novel insights into biological and environmental interactions influencing the phenotypic response. Overall, our work provides new insights into the factors influencing the phenotypic manifestations of DS and reinforces the importance of genetic diversity in studying complex traits.Item Impact of the NAD+ salvage pathway on the motor system and bioenergetics(University of Missouri--Columbia, 2023) Lundt, Samuel; Ding, ShinghuaNicotinamide adenine dinucleotide (NAD+) is a metabolite pivotal to numerous cellular functions, including energy metabolism, DNA repair, and protein modification. The majority of NAD+ is generated by the NAD+ salvage pathway, which is rate limited by nicotinamide phosphoribosyltransferase (NAMPT). NAMPT and the NAD+ salvage pathway are critical to most cell types, but are especially important to neuronal health and function. Additionally, the NAD+ salvage pathway is increasingly being investigated for being involved in neurodegenerative diseases. Recently, the importance of NAMPT to motor and neuromuscular junction (NMJ) activity and survival has been reported. However, how the NAD+ salvage pathway affects NMJ function and what metabolic pathway are dysregulated when the salvage pathway becomes impaired warrants further investigation. In Chapter one, I review intracellular NAD+ homeostasis, NAD+ salvage pathway enzymes, and the importance of NAD+ homeostasis in health and neurodegenerative diseases, specifically ALS. In Chapter two and Chapter three, I used inducible and conditional projection neuron-specific NAMPT knockout mouse, which previously was found to experience profound motor dysfunction and neuron loss. I investigated NMJ structure and function following NAMPT deletion and what benefits NMN administration produces. I also studied how the metabolic and transcriptional profiles in the motor cortex of these knockout mice are altered after NAMPT loss. In Chapter Four, based on the similar phenotypes between the NAMPT knockout mice and ALS mice and NAD+ reduction in ALS mouse model, I investigated how dietary NMN supplementation affects motor behavior and NMJ function in SOD1G93A ALS mice. Overall, the results from these studies provide novel insights into how the NAD+ salvage path is critical for NMJs and what metabolic stress and signaling pathways are responsible for the neuronal death after NAMPT deletionItem Neurochemical, epigenetic, and structural brain changes associated with prenatal stress exposure, and the mitigating effects of DHA(University of Missouri--Columbia, 2023) Woo, Taeseon; Beversdorf, David Q.The Developmental Origins of Health and Disease (DOHaD) hypothesis posits that in utero stress exposure can modify developmental trajectories, influencing adult health. Research indicates that maternal stress can negatively impact neurodevelopment, especially in individuals genetically predisposed to stress. Such stress has been linked to various neurodevelopmental disorders, including autism spectrum disorder (ASD). Our previous research showed that stress-sensitive polymorphisms in the serotonin transporter (SERT) gene may interact with environmental stress during pregnancy, increasing ASD risk. Offspring of stress-exposed mice with one SERT gene copy missing (SERT-het) exhibited autism-related behaviors, indicating heightened stress susceptibility. This dissertation's first study examines if prenatal docosahexaenoic acid (DHA) supplementation mitigates autism-related behaviors in stress-exposed SERT-het mice and how it affects lipid peroxidation and brain structure. DHA, an abundant omega-3 fatty acid in mammalian brains, influences brain development and maintenance. DHA supplementation in stress-exposed SERT-het (SERT-het/stress) mice reduced autismxi related behaviors due to prenatal stress, although lipid peroxidation remained unchanged. The second study investigates microRNA (miRNA) as a potential maternal biomarker for neurodevelopmental changes linked to gene-environment (G x E) interactions. We previously identified differentially expressed (DE) miRNAs in blood samples from prenatally stress-exposed mothers with short SERT alleles (S-allele) and ASD-affected children, suggesting a possible blood molecular signature for ASD-related G x E interactions. Therefore, in the second study, we assessed maternal DE miRNA profiles in the SERT-het/stress mouse model at embryonic day 21 (E21) and postnatal day 60 (PD60). The SERT-het/stress group exhibited differential expression of 3 miRNAs at E21 and 13 miRNAs at PD60, which correlated with behavioral findings. In the specific population of S-allele carriers with prenatal stress, these miRNAs could potentially act as indicators for G x E interactions in ASD and demonstrate temporal variability. These studies provide evidence for beneficial effect of DHA and epigenetic alterations associated with the G x E interaction which we hope will lead to better understanding of the mechanisms and eventually treatments of ASD, resulting from prenatal stress exposure in genetically stress susceptible individuals.