Neuroscience and Neurobiology Commons^™

Administering A Mitophagy Inducing Compound (Mic) To Suppress Neuropathology In A Mouse Model Of Alzheimer’S Disease, Zachary Mayeri

Natural Sciences and Mathematics | Biological Sciences Master's Theses

Despite FDA-approved amyloid-beta (Aβ) therapies in Alzheimer’s disease (AD), Tau pathology remains untreated and is closely linked to cognitive decline. Mitophagy, the process of mitochondrial degradation, is vital for maintaining neuronal health, and its dysregulation is implicated in AD. Recently, our lab identified a mitophagy inducing compound (MIC) that extends the lifespan of C. elegans. We hypothesized that MIC would significantly mitigate neuropathology in an AD mouse model. In this study, aged 3x-Tg AD mice were fed an MIC-containing diet, and immunohistochemistry (IHC) was performed on hippocampal tissue to visualize Aβ and phospho-Tau (pTau) lesions. While MIC had little …

Peripheral Neuroimmune Mechanisms Of Chronic Back Pain, Aleyah Esther Goins

Biomedical Sciences ETDs

Chronic back pain (CBP) affects 1 in 10 people worldwide, reducing mobility, productivity, and quality of life. Despite its prevalence, non-addictive treatments remain limited due to an incomplete understanding of chronic pain mechanisms. This dissertation examines peripheral neuroimmune interactions in CBP using a urokinase-type plasminogen activator (uPA)-induced mouse model (uPA-CBP). uPA, a pro-inflammatory serine protease, was injected into the L2/L3 lumbar spinous ligament, inducing prolonged mechanical and cold hypersensitivity. Flow cytometry of dorsal root ganglia (DRG) showed increased CD45+CD11b+ myeloid cells in males and CD45+CD3+CD4+ lymphocytes in females. DRG neurons from male uPA-CBP mice exhibited heightened action potential firing. Pharmacological …

Apolipoprotein E4, Tauopathy, And Brain Injury: Molecular Insights Into Alzheimer's Disease Pathology, Nashanthea J. Roland

Theses & Dissertations

Alzheimer’s disease (AD) is the world’s leading cause of dementia, characterized by progressive atrophy of the hippocampal and cortical brain regions, synapse damage and loss, and a buildup of senile plaques and neurofibrillary tangles composed of β-amyloid peptides and hyperphosphorylated tau, respectively. While age is the most significant risk factor for developing AD, apolipoprotein E4 (APOE4) is the strongest genetic risk factor for AD. Although it is known that APOE4 influences tau pathology, the molecular mechanisms by which APOE4 drives AD pathogenesis and progression remain unclear. In addition to intrinsic contributions to AD, there are many extrinsic factors that can …

The Role Of Presynaptic Proteins In Alcohol Sensitivity And Tolerance, Madhumitha Gundluru

Honors Theses

Mammalian Unc13 (Munc13) and Drosophila Unc13 (Dunc13) are presynaptic active zone proteins essential for synaptic vesicle docking and priming in a neuron. Alcohol binds to the C1 domain of Munc13, which inhibits DAG binding. The reduction in DAG binding by Munc13 decreases the probability of vesicle fusion with the membrane, decreasing neurotransmitter release. Heterozygotes for a Dunc13 loss-of-function allele are behaviorally resistant to alcohol, physiologically resistant to alcohol, molecularly resistant to alcohol, and self-administer significantly more alcohol than control flies. Therefore, genetically reducing Dunc13 mimics a state of alcohol tolerance in the fly. The two main Dunc13 isoforms, Dunc13A and …

Neurodegenerative Disease Mechanisms: Mitochondrial Impairment, Tau Aggregation, And Neuroinflammation As Central Drivers Of Disease Progression, Luis D. Estrella

Theses & Dissertations

The study of the intricate molecular mechanisms behind the pathology of neurodegenerative diseases has become a primary research area in the past decades. The major branches of these studies involve both disease progression and disease pathogenesis, in which neuroscientists have studied, and continue to study, the role that mitochondrial dysfunction, aberrant protein aggregation (like Tau), and immune cell reactions have on these. However, more recent studies have shined light to the fact that these three pathological features are not independent from one another and that their synchronous contributions may be the ultimate driver of neurodegeneration. This dissertation encompasses four different …

Mitochondrial Network Expansion And Loss During Oligodendrocyte Life And Death, Xhoela Bame

Dartmouth College Ph.D Dissertations

Oligodendrocytes are the myelinating cells of the central nervous system, known for modulating signal transmission, refining neural circuits, and providing metabolic support to axons. Oligodendrocytes are generated throughout life from oligodendrocyte precursor cells (OPCs) and are damaged or lost in demyelinating and neurodegenerative diseases and age-related pathologies. Thus, understanding the cellular checkpoints that occur during the generation and degeneration of oligodendrocytes is crucial for maintaining their population in health and recovering it in disease and aging.

Using high-resolution optical imaging, I have discovered a dynamic redistribution and subcellular partitioning of mitochondria during oligodendrogenesis. Mitochondria transiently expanded towards the differentiating OPC …

The Effects Of Pfos Exposure On Zebrafish Dopaminergic Neurodevelopment, Allison G. Fletcher

Departmental Honors & Graduate Capstone Projects

Per- and polyfluoroalkyl substances (PFAS) are a group of environmental contaminants that cause disruptions to the nervous and endocrine systems. Perfluorooctanesulfonate (PFOS) is considered one of the most disruptive PFAS to the nervous system, and may disrupt neurodevelopment of the dopaminergic system, which has been linked to neurodevelopmental disorders like Attention Deficit/Hyperactivity Disorder (ADHD) in humans. I hypothesized that early life PFOS exposure disrupts the development of the dopaminergic system. To test this hypothesis, I exposed zebrafish to 0.05, 0.5, and 5.0 mg/L PFOS through 5 days of embryonic and larval development. To assess acute effects of PFOS on the …

African Sleeping Sickness: From Basic Biology To Future Directions, Riddhi R. Patel

All Theses

African Sleeping Sickness is a Neglected Tropical Disease (NTD) which poses a significant health risk to impoverished populations in 36 Sub-Saharan African countries. It is a devastating disease caused by the protozoan parasite Trypanosoma brucei, which is transmitted to mammals via the bite of infected tsetse flies. The disease manifests in two stages: the hemolymphatic stage and the meningoencephalitic stage. In the latter stage, it invades the Central Nervous System (CNS) and can be fatal if left untreated. It is caused by morphologically indistinguishable species of Trypanosoma brucei in both humans and animals, where in humans it is known as …

Rod Photoreceptor Regeneration In A Zebrafish Model With Retinitis Pigmentosa, Eyad Shihabeddin

Dissertations and Theses (Open Access)

A cellular hallmark of inherited retinal degenerative diseases is progressive loss of photoreceptors until one is completely blind. Unlike mammalian models, Zebrafish have the ability to naturally regenerate their neurons after injury or disease is detected. We have generated a zebrafish model with the most common autosomal dominant form of the inherited retinal degenerative disease known as Retinitis Pigmentosa. We utilize immunohistochemistry, single-cell RNA sequencing, several analysis tools, behavioral assays and oligonucleotides to characterize our zebrafish model and identify the transcription factors necessary for rod photoreceptor regeneration. We show that our zebrafish model has continuous degeneration and regeneration of rod …

Assessing The Behavioral Impact Of Pyridostigmine Bromide In Rats, Noah A. Martin

Honors Theses

Pyridostigmine bromide (PB) is an organophosphate (OP) nerve agent prophylactic used to protect warfighters against chemical warfare agents. OPs inhibit the neural enzyme acetylcholinesterase (AChE) in the brain. This leads to the buildup of acetylcholine, causing respiratory failure, seizures, and death. PB functions by inhibiting ~30% of peripheral AChE temporarily, protecting the enzymes so that the body is able to restore sufficient cholinergic function post-exposure. PB does not cross the blood-brain barrier, though it may still indirectly affect toxicity in the brain due to repeated AChE inhibition throughout treatment, or by inhibition of non-target ChE’s in the blood. The aim …

Effects Of Pfos On Zebrafish Dopaminergic Neurodevelopment, Allison G. Fletcher

Research and Creativity Symposium

Per- and polyfluoroalkyl substances (PFAS) are a group of environmental contaminants that cause disruptions to the nervous and endocrine systems. Perfluorooctanesulfonate (PFOS) is considered one of the most disruptive PFAS to the nervous system, and may disrupt neurodevelopment of the dopaminergic system, which has been linked to neurodevelopmental disorders like Attention Deficit/Hyperactivity Disorder (ADHD) in humans. I hypothesized that early life PFOS exposure disrupts the development of the dopaminergic system. To test this hypothesis, I exposed zebrafish to 0.05, 0.5, and 5.0 mg/L PFOS through 5 days of embryonic and larval development. To assess acute effects of PFOS on the …

Neuronal Cftr: A Study Of Subcellular Localization And Interactions With Implications For A Role In Synaptic Transmission, Brandon J. Leviskas

LSU Doctoral Dissertations

Protein-protein interactions vary among cell types and the localization of these interactions help to define protein function. The function of cystic fibrosis transmembrane conductance regulator (CFTR) is well established in the context of epithelial tissue due to the debilitating effects of its mutations that cause the disease cystic fibrosis. While in neurons a role has been established in our lab for CFTR in the regulation of cytosolic Cl- in retinal amacrine cells (ACs). This research sets out to learn if CFTR has a synaptic role. Exploring this potential role, localization of CFTR was examined using fluorescent and immunogold labeled transmission …

Determinants Of Neuronal Viability Following Spreading Depolarization, Michael C. Bennett

Biomedical Sciences ETDs

Spreading depolarizations (SDs) are massive, slowly propagating waves that cause near-complete neuroglial depolarization and are energetically demanding for the brain. Past studies have established SDs as key contributors to secondary injury in tissue that lacks the metabolic supply to meet the energetic burden of repolarization after SD. Efforts to identify the mechanisms that cause deleterious consequences following SD have been ongoing, with significant results showing that blocking excitotoxic levels of Ca²⁺ from entering neurons through NMDA receptors prevents detrimental outcomes. While these studies have advanced the field, other mechanisms may also contribute to the metabolic burden of SD. This …

The Role Of Cholinergic Ventral Pallidum Cells In Effortful Motivation, Elizabeth A. Bien

Dartmouth College Ph.D Dissertations

Maladaptive reward-seeking behavior can be driven by one of several different components including excessive craving elicited by cues that predict rewards, failing to effortfully pursue rewards when it is beneficial to do so, and compulsively seeking rewards when it is no longer advantageous to do so. This thesis includes experiments focusing on these three different components of reward-seeking behavior to better understand how reward-seeking can become maladaptive. First, we wanted to examine the role that sex plays in the acquisition and compulsiveness of sign-tracking behavior in the Long Evans rat, a strain that is commonly used as the background for …

The Role Of The Female Reproductive Cycle In Social Communication And Relevance To Mental Health, Julissa Amaro Castillo, Fernando Dominguez, Ariana Hinojosa, Giselle Padilla, Mario Gil

Research Symposium

The female reproductive cycle is characterized by fluctuating hormones, including estrogens and progesterone, that are involved in reproductive health; however, they have also been linked to disorders like Premenstrual syndrome (PMS), Premenstrual Dysphoric Disorder (PMDD), mood swings, depression and others. The goal of this study is to use the Syrian hamster (Mesocricetus auratus) as an animal model to examine the influence of the reproductive cycle and hormones on behavior. Scent-marking activity known as flank marking is exhibited by territorial or sociable animals. In essence, animals mark their territory or convey information such as reproductive status by rubbing their flanks or …

Effects Of Arginine-Vasopressin In The Brain On Cardiovascular Function In A Psychosocial Stress Animal Model, Esmeralda Lopez-Garcia, Ariana V. Hinojosa, Esperanza I. Alaniz, Fernando Dominguez, Giselle Padilla, Mario Gil

Research Symposium

Background: Psychosocial stress impacts cardiovascular health, increasing the risk of events like myocardial infarction (MI), stress cardiomyopathy, and neuropsychiatric disorders, including Major Depressive Disorder (MDD) and Anxiety. However, our understanding of the biological mechanisms that connect psychosocial stress with negative cardiovascular and psychological outcomes remains incomplete. Arginine-vasopressin (AVP) is linked to both mental and physical health by regulating social behavior, blood pressure, and anxiety-related behaviors. This study investigates the potential cardioprotective effects of the neuropeptide AVP, in an effort to generate evidence that it may strengthen heart function and lessen the severity of adverse cardiovascular events caused by stress, brain …

Exploring The Effects Of Serotonin And Ssris On The Neurological, Behavioral, And Cardiovascular Systems Under Induced Stress –Using The Animal Model Of The Syrian Hamster, Ariana V. Hinojosa, Esperanza I. Alaniz, Esmeralda Lopez-Garcia, Giselle Padilla, Fernando Dominquez, Mario Gil

Research Symposium

Background: Serotonin is a neurotransmitter that has been found to have a wide range of effects on not just the neuropsychological processes but has also been found to exert effects outside the central nervous system (CNS); regulating numerous biological processes, such as metabolism, gastrointestinal system, reproductive function, and even the cardiovascular system. However, there is still a limited understanding of how serotonin affects all these systems due to its complexity and ability to regulate homeostasis. This project aims to create a stronger foundation of knowledge about serotonin and its influence on the interaction between the CNS, behavior, and cardiac function …

Uncovering The Mechanisms Of Glioblastoma Relapse Prevention With Niclosamide And Camptothecin Treatment, Xiaoqian Fang, Araely Ruiz, Eunseo Yang, Brianna Morin, Kimberly Herrera-Toscano, Megan Szobody, Josue Fonseca, John-Beloved Osho, Raquel Lara

Research Symposium

Background: Glioblastoma multiforme (GBM) is the most common and lethal malignant primary brain tumor for which the development of efficacious chemotherapeutic agents remains an urgent need. In our previous studies, we demonstrated that niclosamide and camptothecin (CPT) synergistically suppressed the proliferation in human glioblastoma U87 MG cells. Recently, we observed that U87 MG cells failed to resume growth after the combined treatment was removed, a phenomenon not seen with either agent alone. We aimed to explore the sustained anti-tumor effects of niclosamide and CPT in GBM.

Methods: Human glioblastoma U87 MG cells were treated with 5 mM niclosamide, 5 mM …

The Impact Of Diabetes On Neurovascular Integrity: A Special Focus On Pericytes And Endothelin-1, Mia Edgerton

MUSC Theses and Dissertations

Diabetes increases the risk of stroke and Vascular Contributions to Cognitive Impairment and Dementia (VCID). Diabetes also dysregulates the endothelin (ET) system. ET-1-mediated constriction of brain microvascular pericytes (BMVPCs) has been shown to contribute to brain hypoperfusion. However, there is a loss of BMVPCs in VCID, but underlying mechanisms of pericyte degeneration are poorly studied. ETA receptor activation can instigate phenotypical changes and cellular senescence in endothelial cells. . There is also emerging evidence that ETB receptor agonism improves outcomes in patients with cerebral ischemic stroke, but long-term effects, especially in diabetes, are unknown. Therefore, this study aimed to determine …

In-Silico Modeling And Characterization Of Kcc2 Protein Interaction With A Small Molecule Direct Agonist Identifies Potential Binding Sites For Modulating Behaviors Associated With Substances Of Abuse, William Hai Dang Ho, Alfred Amendolara, Kenyon Mitchell, Jaden Miner, Ruth Northcott, Braxton Bingham, Andrew J. Payne

Annual Research Symposium

Purpose

KCC2 is a potassium-chloride cotransporter that plays a critical role in neuronal function by regulating GABAergic signaling via chloride gradients. Maintaining this concentration gradient is crucial for balancing excitation and inhibition in the brain. While KCC2 dysregulation has been implicated in epilepsy and seizures, recent studies suggest that KCC2 inhibition results in phenotypes mirroring those seen in chronic opioid dependence. As such, increasing evidence support KCC2 being a potential therapeutic target for modulating behaviors associated with substances of abuse. Currently, only a few direct small molecule agonists against KCC2 have been reported, and no definitive active site on the …

Investigating The Effects Of Resveratrol On Opioid-Induced Hyperalgesia, Bryana Cox, Thien Do, Ashlyn Hughes, Zane Kingsbury, Keara Leroy, Andrew J. Payne

Annual Research Symposium

Opioid-induced hyperalgesia (OIH) is an adverse effect of chronic opioid therapy, characterized by increased sensitivity to pain. This study will seek to determine if using resveratrol supplementation as an indirect enhancer to increase the expression of the KCC2 membrane transporter can alleviate the symptoms of OIH in human subjects.

Use Of Synthetic Water-Soluble Kcc2 To Modulate Chloride Homeostasis In Cultured Dopamine-Neuron-Like Cells, Mason Terry, Andrew Payne, Dario Mizrachi

Annual Research Symposium

No abstract provided.

Comprehensive Sumo Proteomic Analyses Identify Hiv Latency-Associated Proteins In Microglia., Fergan Imbert, Dianne Langford

Rowan-Virtua School of Osteopathic Medicine Departmental Research

SUMOylation, the post-translational modification of proteins by small ubiquitin-like modifiers, plays a critical role in regulating various cellular processes, including innate immunity. This modification is essential for modulating immune responses and influencing signaling pathways that govern the activation and function of immune cells. Recent studies suggest that SUMOylation also contributes to the pathophysiology of central nervous system (CNS) viral infections, where it contributes to the host response and viral replication dynamics. Here, we explore the multifaceted role of SUMOylation in innate immune signaling and its implications for viral infections within the CNS. Notably, we present novel proteomic analyses aimed at …

Anatomy And Variations Of The Carina And Its Cartilaginous Makeup: A Cadaveric Study, Chung Yoh Kim, Kristen Rizzuto, Daniel Tahan, Devendra Shekhawat, Rarinthorn Samrid, Yoko Tabira, Stephen J. Bordes, Joe Iwanaga, R. Shane Tubbs

School of Medicine Faculty Publications

Purpose: The carina, located at the bifurcation of the trachea, has been regarded as a part of the trachea. Although clinically useful as an anatomical landmark, studies of its detailed morphology are lacking in the literature. Methods: The distal trachea and left and right main bronchi were harvested from 32 cadavers and the carina studied using microsurgical dissection, endoscopy, micro-CT, and histology. Results: The right bronchial cartilages were most commonly involved in forming the carina (72.41%), and the left bronchial cartilages were the second most commonly involved (37.93%). The carinal cartilages were slightly deviated to the left of midline in …

An Agent-Based Model Of Microglia And Neuron Interaction: Implications In Neurodegenerative Disease, Cheyenne Ty, Amanda Case, Emmanuel Mezzulo, Abigail Penland, Kamila Larripa

Spora: A Journal of Biomathematics

Whether immune cells protect or harm the brain is an open question depending on context, and their role is implicated in multiple diseases such as Alzheimer's disease, dementia, and other neurological disorders. Microglia, a specific type of immune cell in the central nervous system, play a key role in homeostasis, and genes associated with an elevated risk of Alzheimer's disease correspond with deficiencies in their behavior. We created an agent-based model that incorporates inflammatory signaling, chemotaxis, and phagocytosis of damaged neurons and allows the exploration of crucial pathways in the maintenance of brain health. We specifically investigated pathways related to …

Plasma S100Β Is A Predictor For Pathology And Cognitive Decline In Alzheimer’S Disease, Geetika Nehra, Bryan J. Maloney, Rebecca Smith, Wijitra Chumboatong, Erin L. Abner, Peter T. Nelson, Björn Bauer, Anika M. S. Hartz

UK CARES Faculty Publications

Background Blood–brain barrier dysfunction is one characteristic of Alzheimer’s disease (AD) and is recognized as both a cause and consequence of the pathological cascade leading to cognitive decline. The goal of this study was to assess markers for barrier dysfunction in postmortem tissue samples from research participants who were either cognitively normal individuals (CNI) or diagnosed with AD at the time of autopsy and determine to what extent these markers are associated with AD neuropathologic changes (ADNC) and cognitive impairment.

Methods We used postmortem brain tissue and plasma samples from 19 participants: 9 CNI and 10 AD dementia patients who …

Influences Of Sex, Alcohol, And Stress On Conditioned Fear Responses, Heyam K. Mayberry

MUSC Theses and Dissertations

Learned fear responses are acquired through the identification and association of threatening stimuli with aversive outcomes. Fear responding and the proper maintenance of defensive behaviors is integral to survival. However, without the homeostasis of such systems, fear responses can become maladaptive and lead to dysregulated behavioral responding. Psychological conditions such as alcohol use disorder (AUD) and post-traumatic stress disorder (PTSD) often lead to impairments in fear learning, deficits in fear memory, and heightened fear responses. While there are clear sex differences in the prevalence of both AUD and PTSD, development of either disorder increases the risk for comorbid AUD/PTSD, leading …

Atorvastatin Alters Neuronal Morphology Data Set, Carolyn L. Pytte

Publications and Research

Statins are highly effective and widely prescribed cholesterol lowering drugs. However, statins cross the blood-brain barrier and decrease neural cholesterol in animal models, raising concern that long-term statin use may impact cholesterol-dependent structures and functions in the brain. Cholesterol is a fundamental component of cell membranes and experimentally decreasing membrane cholesterol has been shown to alter cell morphology in vitro. In addition, brain regions that undergo adult neurogenesis rely on local brain cholesterol for the manufacture of new neuronal membranes. Thus neurogenesis may be particularly vulnerable to long-term statin use. Here we asked whether oral statin treatment impacts neurogenesis …

Loss Of Lgl1 Increases Expression Of C-Jun And Dcx In The Svz And Rms Of The Mouse Brain, Madison Leigh Gutierrez

Cal Poly Humboldt theses and projects

Glioblastoma (GBM), the most aggressive and treatment-resistant subtype of glioma, accounts for the majority of brain tumor–related mortality. A defining feature of GBM is its ability to invade healthy brain tissue through extensive cell migration, which severely limits the effectiveness of surgical and pharmacological treatments. Increasing evidence suggests that GBM cells activate gene programs known to drive normal neural stem and progenitor cell (NSPC) migration; however, the precise molecular mechanisms shared between NSPCs and GBM cells remain poorly understood. Lethal (2) giant larvae 1 (Lgl1), a conserved cortical cytoskeletal protein, has emerged as a key regulator of polarity and migration. …

Leveraging Clinical Standards To Improve The Translational Relevance Of Therapies For Experimental Spinal Cord Injury, Aaron L. Silverstein

Theses and Dissertations--Neuroscience

Efforts to improve treatment of spinal cord injury (SCI) often use animals to develop effective therapeutics, intending to improve the survival and the quality of life of persons with SCI. Over half of all SCIs in the United States occur at the cervical level and often cause locomotor deficits and life-threatening breathing dysfunction. Thus, my dissertation is focused on this important patient population.

After beginning with a description of translational research and surveying SCI from a clinical standpoint, I turned to describe experimental models of cervical SCI and more detailed neuroimmunological findings relevant to my work. Then, I conducted a …