Neuroscience and Neurobiology Commons^™

Investigating The Effects Of In-Vivo Therapeutics Hypoxia Treatment Paradigms In Neurite Outgrowth Patterns, Jae Hyun Yoo

Theses and Dissertations--Medical Sciences

Spinal cord injury, specifically in the cervical C3-C4 region of the cervical spine, contributes to impaired breathing and a diminished quality of life. Therefore it is important to find effective and safe therapeutics to restore breathing function. Indeed, there are a myriad of research being performed in addition to valuable collaboration amongst different institutions. As such, inspired by a previous experiment, we decided to test our hypothesis that an enriching environment consisting of different hypoxic environments - sustained and intermittent hypoxia alongside normoxia - would result in neurite outgrowth. Moreover, we hypothesized that sustained hypoxia would result in the greatest …

Peripheral And Central Glucose Flux In Type I Diabetes, Jelena Anna Juras

Theses and Dissertations--Neuroscience

Diabetes is a complex metabolic disorder, of which high blood glucose concentration is the primary hallmark. Type I diabetes mellitus (T1DM) is characterized by the lack of insulin production, due to a poorly understood autoinflammatory cascade. In the words of historian Barnett “Diabetes may no longer be a death sentence, but for more and more people in the 21st century, it will become a life sentence”, making it the focal point of many research groups. It is estimated that around 20 million individuals worldwide live with T1DM.

Effects of long-term chronically elevated blood glucose are not only seen in micro/macro-vascular …

Apoe Genotype And Cerebral Glucose Metabolism: A Multi-Omics Approach, Holden C. Williams

Theses and Dissertations--Physiology

Apolipoprotein E (APOE) is encoded by the APOE gene, present in humans as three main isoforms (E2, E3, and E4). E4 carriers face up to a 15-fold increased risk for developing late-onset Alzheimer’s disease (AD), while E2 carriers are protected. Understanding the risk conferred by E4 has been an extensive research focus for nearly three decades, but the exact mechanism has yet to be proven. Many studies have demonstrated attenuated roles of E4 in classical hallmarks of AD, notably amyloid processing and neurofibrillary formation, which normally present later in disease progression. How APOE influences hallmarks that present much earlier are …

Uncovering The Role Of Apoe4 On Alzheimer’S Disease-Related Neuroinflammation, Courtney Marie Kloske

Theses and Dissertations--Physiology

Alzheimer’s disease (AD) is the most common neurodegenerative disease and is characterized by two hallmark pathologies: amyloid-beta plaques (Ab plaques) and hyperphosphorylated, aggregated tau tangles. These pathologies are typically accompanied by the presence of neuroinflammation which is primarily mediated by microglia. Interestingly, several genetic risk factors that increase the risk of AD also have direct impacts on neuroinflammation. Of interest, Apolipoprotein E (ApoE) is the largest genetic risk factor for AD. ApoE has three isoforms- E4 confers an increased risk for AD, E3 is considered the “control” phenotype, and E2 is protective against AD. E4 plays a role in virtually …

Investigation Of The Neuroprotective Effects Of Grape Seed Extract On Trigeminal Ganglion Primary Cultures, Sophia Rose Antonopoulos

Graduate Theses/Dissertations

Migraine and temporomandibular disorders (TMD) are prevalent, debilitating orofacial pain conditions involving peripheral and central sensitization of the trigeminal system. The pro-inflammatory neuropeptide calcitonin gene-related peptide (CGRP), which is synthesized and secreted from trigeminal ganglion neurons, is implicated in the underlying pathology of migraine and TMD. Secreted CGRP modulates the excitability state of neurons and glial cells that express CGRP receptors. Recent studies from our lab in preclinical models of migraine and TMD have provided evidence that dietary supplementation with a proanthocyanin-enriched grape seed extract (GSE) inhibits trigeminal pain signaling. The effect of GSE was blocked by an antagonist of …

Anatomical Characterization Of Descending Projections Of Lateral Hypothalamic Glutamatergic And Gabaergic Neurons, Jeremy Lesser

Holster Scholar Projects

Important innate behaviors in mammals, such as sleep-wake regulation, arousal, eating, drinking, and stress, are associated with the lateral hypothalamic area (LHA). The LHA is a complex brain region consisting of broad populations of either excitatory glutamatergic neurons or inhibitory GABAergic neurons. Recent studies have revealed dense and heterogeneous fibers from both LHA populations projecting to neuromodulatory regions in the midbrain and brainstem, including the tuberomammillary nucleus (TMN), ventral tegmental area (VTA), dorsal raphe (DR), and locus coeruleus (LC). Viral tracing and immunohistochemistry were utilized to characterize the anatomy of LHAVGLUT2 and LHAVGAT projections to the aforementioned regions in an …

Simulation Of An Inflammatory Model Using Schwann Cells, Caitlyn E. Henry, Peyton Kimmel, Mackenzie Wilcox, Angela Asirvatham

SURF Posters 2022

Schwann cells are a type of glial cell in the peripheral nervous system that produce the myelin sheath surrounding neuronal axons. This myelin insulates the neurons and promotes the rapid conduction of electrical impulses throughout the body. Schwann cells have also been found to play a critical role in neuron repair following nerve injury. During nerve injury, the myelin sheath is damaged, stimulating Schwann cells to release cytokines, or inflammatory mediators, that recruit immune cells to the site of injury so that the myelin debris can be cleared, and repair can take place.1 Then neuronal growth is facilitated by heregulin …

Investigating Mechanisms Of Injury And Intervention In A Novel In Vitro Model Of Traumatic Brain Injury In Organotypic Hippocampal Slice Cultures, Julia Elaine Jagielo-Miller

Theses and Dissertations--Psychology

Traumatic brain injuries (TBIs) impact millions of individuals each year and can pose long term consequences. Despite numerous attempts, no medication has been approved by the FDA to treat TBIs. The causes of these failed trials are multifaceted, but in part can be attributed to the complex nature of TBIs, as well as a lack of sufficient pre-clinical data. In vitro models of TBI are an important tool to help understand the cellular changes seen following the injury, in a highly controlled environment. For the following experiments, a novel model of TBI was used to injure organotypic hippocampal slice cultures, …

Making The Invisible Visible: Mapping Chronic Pain Through Art, Caroline Young

Scripps Senior Theses

This Studio Art thesis explores how I use my art practice as a chronic pain healing process. It draws on the fundamentals of the neuroscience behind pain and the implications of this science for people with chronic pain. People with chronic pain often turn to alternative healing techniques in their search for relief; my own alternative healing approach comes from my art practice of “pain mapping."

The artistic healing process that I have developed takes inspiration from chronically ill artists such as Frida Kahlo and Anna Cowley Ford. The artistic mapping of my pain that I have developed primarily uses …

An Investigation Of Hhv6'S Impact On The Cognitive Progression And Microglial Changes In An Alzheimer's Disease Cohort, Charles E. Seaks

Theses and Dissertations--Physiology

The role of herpesviruses and, more specifically, HHV6 in the development of Alzheimer’s disease (AD) and associated cognitive decline is still being investigated. High ubiquity and prevalence in the population have led to a high degree of skepticism about HHV6 as a potential contributor to cognitive decline and dementias. However, recent evidence related to another herpesvirus, herpes simplex virus 1, suggests that reactivation, not carriage, of the virus may be the key factor to explain the dissonance between the virus’ ubiquity and contributions to dementias. With that in mind, we set out to assess cases from the Sanders-Brown Center on …

Stress And The City: The Impacts Of City Living And Urbanization On Mental Health, Natalie Akins

Scripps Senior Theses

Urbanization is causing a demographic and cultural shift to the landscape of cities across the globe. Although urban living can be advantageous for both individual and societal growth, it can negatively affect mental health and wellbeing. Individuals living in urban environments have an increased risk for mental disorders like depression and schizophrenia. Certain challenges common in urban environments and associated with increased stress, may be causing the increase with mental illness. Chronic stress and the subsequent hyperactivation of the hypothalamic-pituitary-adrenal axis and sustained synthesis of glucocorticoids is detrimental to metabolic, endocrine, and immunologic processes. The overexposure to glucocorticoids can lead …

The Role Of Word Knowledge In Error Detection: A Challenge To The Broken-Error-Monitor Account Of Dyslexia, Lindsay N. Harris, Benjamin Creed, Charles A. Perfetti, Benjamin Rickles

Faculty Articles, Papers, and Other Scholarship

Dyslexic children often fail to correct errors while reading aloud, and dyslexic adolescents and adults exhibit lower amplitudes of the error-related negativity (ERN)—the neural response to errors—than typical readers during silent reading. Past researchers therefore suggested that dyslexia may arise from a faulty error-detection mechanism that interferes with orthographic learning and text comprehension. An alternative possibility is that comprehension difficulty in dyslexics is primarily a downstream effect of low-quality lexical representations—that is, poor word knowledge. On this view the attenuated ERN in dyslexics is a byproduct, rather than a source, of underdeveloped orthographic knowledge. Because the second view implies a …

Lack Of Imagination Can Bias Our View Of Animal Sentience, Brian Key, Deborah Brown

Animal Sentience

How an animal reacts to a sensory stimulus is often used to assess whether that animal can experience feelings such as pain and pleasure. This behavioural path is typically complemented with reference to how a human would normally respond to and experience an analogous stimulus. Together, these approaches can lead to a “hard to imagine otherwise” argument for feelings. It is time to go beyond these qualitative assessments and to now determine whether a nervous system can execute the neural functions necessary for sentience.

A Combinatorial 5-Htr Expression Pattern Within The Ventral Projection Neurons Of The D. Melanogaster Olfactory Circuit., Mohd Freezely Ezzani Bin Mazri

Graduate Theses, Dissertations, and Problem Reports (ETD)

Neuromodulation allows neurons within a circuit to respond to stimuli from the environment according to the correct ecological value, context, and internal state of the animal. Serotonin (5-HT) is a neuromodulator that can generate different outcomes based on its target’s serotonin receptor (5-HTR) expression by affecting secondary messenger cascades. Within the Drosophila olfactory system, ventral projections neurons (vPN) express all five insect 5-HTR that project into two olfactory processing regions, the antennal lobe (AL) and the lateral horn (LH). The significance of this 5-HTR expression is unknown. In this study, I theorized the patterns of 5-HTR expression of vPNs. I …

Exploiting Modulation Of The Blood-Brain And Blood-Tumor Barrier Permeability By Translational Focused Ultrasound For Therapeutic Delivery To Cns Metastases, Tasneem A. Arsiwala

Graduate Theses, Dissertations, and Problem Reports (ETD)

Transcranial low-intensity focused ultrasound is a unique technology to modulate the integrity of tight endothelial junctions and transiently increase BBB/BTB permeability to enhance therapeutic delivery. Despite promising early studies, present literature lacks agreement on key experimental conditions, which restricts our knowledge and the technique's widespread translation. This dissertation first provides a critical review of the current gaps in knowledge regarding the universal use of LiFUS in preclinical and clinical use. We then identify key parameters for translational and predictable opening of the BBB using a 3T MRI coupled with a clinical device. Our investigation highlights that passive permeability of the …

Examining Development And Function Of Pretectal Visual Neural Circuits In Gs Homeobox 1 Mutant Zebrafish, Alexandra Rose Schmidt

Graduate Theses, Dissertations, and Problem Reports (ETD)

Brain development requires a coordinated genetic code to regulate initial cell identity determination, migration, and connectivity, to establish function of neural circuits. Independent neural circuits underlie our ability to produce both complex and innate behavioral responses to sensory stimuli that are often conserved across vertebrate organisms. Sensory processing disruptions are associated with several neurodevelopmental disorders (NDDs). Therefore, gene mutations altering neurodevelopment can lead to changes influencing structure and function of individual neural circuits, causing behavioral deviations in sensory responsiveness. Crucial gene networks that define functional properties of sensory domains are often explored using non-mammalian vertebrate models, such as the zebrafish. …

Microglia Distribution In The Lateral Ventricles Following Treatment Of Lysolecithin Model Of Multiple Sclerosis, Spencer James Wilson

Browse all Theses and Dissertations

Multiple sclerosis (MS) affects an estimated one million people in the US alone (Wallin et al., 2019). We modeled MS in rats using lysolecithin injection into the corpus callosum to diminish motor function unilaterally through demyelination, meanwhile treating the injury with Fluoxetine, Ibuprofen, and ascorbic acid (FIAA) to increase neurogenesis and oligodendrogenesis. Motor function was assessed using the Montoya Staircase test pre- and post-surgery. Motor capabilities recovered in the contralateral limb, but not in the ipsilateral, and recovery was not significantly affected by treatment. We identified microglia by CX3CR1 and examined its distribution in the adult neurogenic niche, the SVZ …

Strong Inferences About Pain In Invertebrates Require Stronger Evidence, Edgar T. Walters

Animal Sentience

Evidence for sentience in animals distantly related to humans is often sought in observations of behavioral and neural responses to noxious stimuli that would be painful in humans. Most proposed criteria for painful sentience in “lower” animals such as decapod crustaceans have no necessary links to the affective (“suffering”) component of pain. The best evidence for painful affect in animals is learned aversion to stimuli associated with noxious experience, and conditioned preference for contexts associated with relief from aversive consequences of noxious experience, as expressed in voluntary behavior. Such evidence is currently lacking for any invertebrate except octopus.

Importin-Mediated Pathological Tau Nuclear Translocation Causes Disruption Of The Nuclear Lamina, Tdp-43 Mislocalization And Cell Death, Robert F. Candia, Leah S. Cohen, Viktoriya Morozova, Christopher Corbo, Alejandra D. Alonso

Publications and Research

Tau is a cytosolic protein that has also been observed in the nucleus, where it has multiple proposed functions that are regulated by phosphorylation. However, the mechanism underlying the nuclear import of tau is unclear, as is the contribution of nuclear tau to the pathology of tauopathies. We have previously generated a pathological form of tau, PH-tau (pseudophosphorylation mutants S199E, T212E, T231E, and S262E) that mimics AD pathological behavior in cells, Drosophila, and a mouse model. Here, we demonstrated that PH-tau translocates into the nucleus of transiently transfected HEK-293 cells, but wildtype tau does not. We identified a putative …

The Price Of “Normal”: Masking In The Autistic Community, Phyllis Elizabeth Holloway

Online Theses and Dissertations

The Autistic community has a rich history that often includes poor mental health outcomes due to the increased stress and anxiety surrounding the push to have “normal” social skills. On Twitter, many autistic people utilize a hashtag to connect with others in the online Autistic community. This qualitative study analyzes the Twitter hashtag, #ActuallyAutistic, to understand masking and camouflaging from the autistic point of view. A qualitative descriptive approach was used to perform this analysis. The themes found emphasize the need for professionals to increase their understanding of the Autistic community’s value and contributions. By improving the ability of non-autistic …