Neuroscience and Neurobiology Commons^™

The Effects Of Deletion Of The Cytoplasmic Domain Of Robo3 On Drosophila, Jessie Agcaoili

Biological Sciences Undergraduate Honors Theses

My research project examines how the deletion of the cytoplasmic domain affects the function of Robo3. If Robo3 is signaling repulsion in response to SLIT this activity should require the cytoplasmic domain. I investigated the functional importance of Robo3 by deleting the cytoplasmic domain of Robo3 using a CRISPR-based technique. This modified gene was then injected into Drosophila embryos where it replaced the normal copy of the gene. Embryos expressing the modified version of robo3 in place of normal robo3 were dissected and examined.

Characterizing Rat Lateral Amygdala Interneurons By Colocalization Of Calcium-Binding Proteins Via Serial Multiplex Immunohistochemistry, Ethan Gasteyer

Honors Scholar Theses

The lateral amygdala is a brain structure that plays an important role in regulating fear and anxiety. Some anxiety disorders are hypothesized to develop from failures in this local inhibitory circuit. Distinct populations of these inhibitory neurons express patterns of calcium- binding proteins and neuropeptides that suggest differences in functionality within the lateral amygdala. Furthermore, these patterns of expression are compared between male and female rats to identify sex differences in the lateral amygdala. Previous studies have reported sex differences in amygdala activation and connectivity, but very little is known about the sexual dimorphism of calcium-binding protein and neuropeptide expression. …

Hypocretin-Receptor Mrna Expression In The Central Amygdala Of Alcohol-Dependent And Non-Dependent Rats, Gabriel Aldridge

Electronic Theses and Dissertations

Hypocretin/Orexin (HCRT) neurotransmission facilitates drug-seeking behavior. HCRT neurotransmission at HCRT-receptors 1 and 2 (HCRT-R1 and -R2, respectively) is implicated in addiction. During the shift to alcohol-dependency, adaptations in neurotransmitter systems occur in reward- and stress-related brain regions. Specifically, neurotransmission systems in the central amygdala (CeA) are modulated by alcohol drinking/exposure. Therefore, this study investigated Hcrtr1 and Hcrtr2 mRNA expression in the CeA of alcohol-dependent rats and in non-dependent controls during acute alcohol withdrawal. Fos mRNA expression in the CeA of alcohol-dependent and non-dependent rats was also determined to assess adaptations in neuronal activation. To our knowledge, this is the first …

Innate Lymphoid Cell Characterization And Ilc2s In Neuroinflammation In Aging And Sex Differences, Alexis Mobley, Alexis S. Mobley

Dissertations and Theses (Open Access)

Aging affects immunologic responses by a global immune system suppression, including dysregulation of cytokine mediators, leading to increased inflammation throughout all systems, termed inflammaging. However, understanding healthy aging mechanisms can bypass this effect. Inflammaging also leads to poor outcomes during brain injury, making immune-targeting therapeutics tantamount to overall brain health and longevity. Moreover, sex affects disease etiology and severity through hormonal and chromosomal sex, as the X chromosome contains most immunology-based genes. Androgens have a generally suppressive effect on the immune system. Additionally, when immune responses are mounted, males are better at CD4+ T cell type (Th1) responses, while females …

The Relationship Between Circadian Rhythms And Neurodegenerative Disease, Christopher Simpson

Honors Projects

Neurodegenerative disease is a pervasive and insidious disease affecting a large proportion of the elderly population. Leading to the degeneration of neural tissue throughout the nervous system, it is a slow and progressive disorder. Because of its nature, it is possible that it has a connection to circadian rhythms. Circadian rhythms are the endogenous approximately 24-hour rhythms of the body commonly associated with the sleep-wake cycle, but they account for much more. This review aims to ascertain the relationship between the two by covering several facets of research pursued in the past five years. Beginning with establishing a basic understanding …

Alzheimer's Disease: A Comprehensive Review Including Personal Experience From Retirement Home Patients, Sydney Fox

Honors Theses

Alzheimer’s Disease is a neurodegenerative illness and disease, the most common type of dementia, and the sixth leading cause of death (Sá et al., 2012). The disease was discovered in 1906 and named after Dr. Alois Alzheimer, a psychiatrist and neuropathologist. Over time, a variety of hypotheses have developed regarding the cause behind this multifactorial disease, and these will be disclosed in a later section. Nonetheless, the disease was first observed in changes of the brain tissue of a woman who was said to have die from an unusual mental illness with many abnormal bumps. These bumps are now recognized …

Investigating The Role Of The Basolateral Amygdala Plays In The Incubation Of Cue-Induced Cocaine Seeking Behavior, Claire Marie Corbett

Graduate School of Biomedical Sciences Theses and Dissertations

Cocaine use disorder is a chronic, relapsing brain disease. Sex and ovarian hormones are known to influence cocaine addiction liability and relapse vulnerability. However, little is known regarding the cellular and synaptic mechanisms contributing to sex differences in relapse vulnerability, including how these measures are influenced by hormonal fluctuations. To investigate sex differences in relapse vulnerability we use a rodent model of cocaine craving and relapse called the incubation model in which cue-induced seeking progressively increases or “incubates” during the first month of withdrawal from extended-access cocaine self-administration. Using this model, we have recently shown that females in the estrus …

Trkb Activity Alters Voluntary Alcohol Consumption In Nondependent Mice, Alfred Amendolara

Annual Research Symposium

No abstract provided.

Novel Methodology For The Investigation Of Dmrt3a Interneurons In Larval Zebrafish, Alfred Amendolara

Annual Research Symposium

No abstract provided.

Prmt5 Interacting Partners And Substrates In Oligodendrocyte Lineage Cells, David K. Dansu, Jialiang Liang, Ipek Selcen, Haiyan Zheng, Dirk F. Moore, Patricia Casaccia

Advanced Science Research Center

The protein arginine methyl transferase PRMT5 is an enzyme expressed in oligodendrocyte lineage cells and responsible for the symmetric methylation of arginine residues on histone tails. Previous work from our laboratory identified PRMT5 as critical for myelination, due to its transcriptional regulation of genes involved in survival and early stages of differentiation. However, besides its nuclear localization, PRMT5 is found at high levels in the cytoplasm of several cell types, including oligodendrocyte progenitor cells (OPCs) and yet, its interacting partners in this lineage, remain elusive. By using mass spectrometry on protein eluates from extracts generated from primary oligodendrocyte lineage cells …

The Effects Of Nuclear Factor Erythroid 2 (Nfe2)-Related Factor 2 (Nrf2) Activation In Preclinical Models Of Peripheral Neuropathic Pain, Paramita Basu, Dayna L. Averitt, Camelia Maier, Arpita Basu

Kinesiology and Nutrition Sciences Faculty Research

Oxidative stress, resulting from an imbalance between the formation of damaging free radicals and availability of protective antioxidants, can contribute to peripheral neuropathic pain conditions. Reactive oxygen and nitrogen species, as well as products of the mitochondrial metabolism such as superoxide anions, hydrogen peroxide, and hydroxyl radicals, are common free radicals. Nuclear factor erythroid 2 (NFE2)-related factor 2 (Nrf2) is a transcription factor encoded by the NFE2L2 gene and is a member of the cap ‘n’ collar subfamily of basic region leucine zipper transcription factors. Under normal physiological conditions, Nrf2 remains bound to Kelch-like ECH-associated protein 1 in the cytoplasm …

Novel Strategies For Glutamate Clearance In The Glia-Deprived Synaptic Hub Of C. Elegans, Joyce Chan

Dissertations, Theses, and Capstone Projects

As the major excitatory neurotransmitter in the mammalian brain, Glutamate (Glu) is critical for normal neuronal physiology. Disruption in Glu clearance results in hyper-stimulation of glutamatergic circuits, potentially leading to excitotoxic neurodegeneration. The canonical model of brain connectivity describes glutamatergic synapses as well insulated and enveloped by glia. These glia express Glu Transporters (GluTs) which work to clear Glu following synaptic activity. However, critical areas of the brain such as the mammalian hippocampus display poor synaptic isolation, which may result in Glu spillover between adjacent synapses and subsequent loss of circuit specificity. How accurate signal transmission is achieved in these …

The Pathophysiological Mechanisms Of Alzheimer's Disease; Investigating Therapeutic Interventions For Disease Onset, Alexandra A. Sandberg

Electronic Theses and Dissertations

Alzheimer’s Disease is a multifarious disease that progressively affects more people as both the proportion of older adults in the population and life expectancy increase in both the United States and worldwide. This devastating disease is a result of rampant neuronal loss in the memory centers of the brain that robs the independence of those who are diagnosed and places a heavy burden on those who care for them. Traditionally speaking, research has focused on the hallmark pathology of amyloid plaques, targeting them to try and prevent disease onset. However, countless failures in clinical trials aimed at this said pathology …

The Effects Of Neuronal Growth Factors On Lps-Activated Schwann Cells, Caitlyn E. Henry, Peyton Kimmel, Angela Asirvatham Ph.D.

Student Research Poster Presentations 2022

Schwann cells (SCs) are the principal support cells of neurons in the peripheral nervous system, that both myelinate axons for the rapid conduction of electrical impulses as well as assist in axonal repair during nerve injury. During nerve injury, SCs secrete tumor necrosis factor alpha (TNF-α)^1,5,6 and other proinflammatory mediators^1,6, attracting macrophages to the site of injury to induce inflammation and clear myelin debris.^1,6 Once the debris is cleared, the neuron stimulates SC proliferation by secreting neuronal mitogens, such as heregulin^3,4, and an unknown factor that activates the cAMP pathway³, an important …

Simulation Of An Inflammatory Model Using Schwann Cells, Caitlyn Henry, Peyton Kimmel, Angela Asirvatham

Student Research Poster Presentations 2022

During peripheral nerve injury, the myelin surrounding the neuronal axons is damaged, initiating an inflammatory response to remove myelin debris. Once myelin debris is cleared, Schwann cells acquire a proliferating phenotype which allows them to grow and divide so that remyelination can occur. The neuron stimulates Schwann cell division by secreting growth factors, like heregulin, and an unknown growth factor that activates the cAMP pathway. Although the role of cAMP in axonal regeneration is well-known, not much has been explored about its function in Schwann cells during nerve injury and inflammation. To simulate an inflammatory environment, the S16 Schwann cell …

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 …

Cellular Activation Following Acute And Chronic Ethanol In Glutamatergic Projection Neurons, Annalise Hassan, Sam Gottlieb, Michael F. Miles Md, Phd

IRBEH/Spit for Science Publications and Presentations

No abstract provided.

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 …

Viral Injection Of Rna Polymerase Ii-Interacting Protein Rprd2 In The Nucleus Accumbens Induces Anxiety-Like Behavior In Mice, Hannah E. Woolard

Theses and Dissertations

Anxiety and its related disorders have become increasingly prevalent as more awareness and acceptance of mental illnesses have come to fruition, especially in the light of the ongoing COVID-19 pandemic. Anxiety can affect anyone regardless of their age, sex, or social status and is currently the most commonly diagnosed mental illness worldwide (Bandelow & Michaelis, 2015). While there are several effective treatments available, the underlying brain mechanisms that cause anxiety are still largely unknown and further research continues to piece together the complex pathophysiology behind this disease. The use of laboratory animal models, such as mice, to induce and observe …

Membrane Palmitoylated Protein Magu-3 Regulates The C. Elegans Locomotor Circuit Via Modulation Of Cholinergic Activity, Henry Richburg

Theses and Dissertations--Medical Sciences

Precise coordination of the activity and transmission in excitatory and inhibitory neural circuits is essential for healthy information flow. Synaptic scaffolding proteins play a key role in the regulation of circuit activity through the localization and organization of receptors, channels, and other synaptic machinery to facilitate signal transduction. Using the C. elegans motor circuit which has both cholinergic (excitatory) and GABAergic (inhibitory) inputs onto muscles, we revealed an unexplored role of a family of scaffolding molecules known as membrane palmitoylated proteins (MPPs). Here, we examined magu-3, a C. elegans ortholog within the membrane palmitoylated protein family, using GFP tagging …

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 …

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 …

Does Bisphenol-A, An Estrogen-Like Environmental Toxin, Disrupt Expression Of The Neuronal Chloride Exporter Protein During Early Brain Development?, Mayra S. Mendez

Cal Poly Humboldt theses and projects

Bisphenol A (BPA), a manufactured compound found in consumer products, is known to adversely affect early brain development by disrupting normal estrogen signaling. Recently, BPA was reported to suppress expression of a gene encoding the neuron-specific chloride ion transporter, KCC2. Human and animal studies show suppressing KCC2 can cause neuronal and behavioral hyperactivity. Therefore, some adverse effects of BPA may be due to KCC2 suppression and consequent neuronal hyperactivity. This study aimed to determine whether BPA exposure during brain development alters KCC2 expression. A secondary purpose was to evaluate whether a new transgenic zebrafish line, KCC2:mCitrine,could be used to track …

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. …

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, …