Molecular and Cellular Neuroscience Commons^™

The Combined Effects Of Physical Exercise And Cognitive Training On Gait Speed And Primary Motor Cortex Metabolism In Individuals With Mild Cognitive Impairment: A 1h-Mrs Analysis, Jack Thomas Emsey Elkas

Electronic Thesis and Dissertation Repository

Mild cognitive impairment (MCI) is a transitional stage before dementia. Altered gait in MCI has been associated with progression to dementia. Using magnetic resonance spectroscopy, a relationship between primary motor cortex (M1) neurochemistry and dual task gait speed has been reported in MCI. Interventional research suggests exercise, cognitive training, and vitamin D supplementation may benefit MCI, yet the combined effect of these treatments on gait speed and M1 metabolism is unknown. Participants with MCI (N=75) were assigned to one of five intervention arms and dual task cost on gait speed and M1 metabolism was assessed before and five months after …

Complement System In Multiple Sclerosis: Its Role In Disease Course And Potential As A Therapeutic Target, Michael R. Linzey

Dartmouth College Ph.D Dissertations

Multiple sclerosis (MS) is a clinically heterogeneous neurological condition characterized by neuroinflammation and neurodegeneration. Relapsing-remitting MS, defined by inflammatory attacks, is the most common initial form of MS and there are currently 23 FDA-approved treatments for these patients. These therapies work primarily by reducing inflammation in the CNS; they do not work well in progressive disease. Therefore, an unmet medical need exists for effective therapeutic options to treat progressive MS (PMS).

In MS, intrathecal immunoglobulins synthesis (IIgS) correlates with disease progression. My goals for this dissertation were to establish the pathological role of IIgS and identify new potential therapeutic …

Role Of Chronic Stress-Induced Neuroinflammation In Rodent Locus Coeruleus Physiology And Anxiety-Like Behaviors, Arthur Anthony Alfonso Reyes

Graduate School of Biomedical Sciences Theses and Dissertations

The locus coeruleus (LC), the primary site of brain norepinephrine (NE), is a key anatomical brain region implicated in the stress response. Stress is a neuroendocrine physiologic response to a stressor that promotes organism survival through adaptive change and restoration of homeostasis. The central stress response, which drives behavioral and physiological change, is primarily mediated by activating the hypothalamic-pituitary-adrenal (HPA) axis. While advantageous in the short term, chronic stress exposure can lead to HPA axis and LC dysregulation, which are thought to contribute to the etiology of anxiety disorders. Previous studies demonstrate the effects of acute stress in increasing LC …

The Protective Effects Of Anthocyanins On Neurons, Abigail Lynn

Pence-Boyce STEM Student Scholarship

Parkinson’s and Alzheimer’s are debilitating neurodegenerative diseases that are largely thought to be exacerbated, and perhaps even caused, by oxidative stress in and around neurons. At the same time, there has been increased research in the field of nutrition and how the foods we eat impact our short- and long-term health. These combined interests have resulted in fascinating studies that have found certain foods, namely plants, can have a variety of medicinal benefits.....The purpose of this study is to determine if plant extracts that have high levels of certain phytonutrients can increase the activity of cellular enzymes that reduce oxidative …

The Role Of Complement In Stroke And Traumatic Brain Injury, Christine Couch

MUSC Theses and Dissertations

Brain and neural injury are a non-specific disease category that includes traumatic brain injury (TBI) and stroke. Both TBI and stroke are common, costly, and leading causes of severe disability in adults. Both stroke and TBI are responsible for substantial disability in working age adults, with stroke being the second leading cause of death worldwide [1] and TBI a major cause of disability in people younger than their 40's [2]. The immune response after brain injury is multifactorial and involves both local and systemic events at the cellular and molecular level. The complement system is a component of both the …

Optical Perturbation Of Protein Kinase A Activity Via Photoactivatable Inhibitor Peptides, Peter Chen

McKelvey School of Engineering Theses & Dissertations

Protein Kinase A (PKA) plays important roles in diverse biological processes such as sleep, long term memory, and synaptic plasticity. In addition, PKA also acts as an integrator of neuromodulator signaling though G protein-coupled receptor activation. However, despite genetic knockout and pharmacological inhibition experiments that demonstrate the importance of PKA, it is unclear where, when, or how PKA plays these roles in cellular physiology and behavior. In order to better understand the function of PKA in these processes, and how neuromodulator signaling drives complex behavioral changes, there exists a need for a method to selectively activate/inactivate PKA with high spatial …

All The Rage: Assessing The Age/Rage Signaling Pathway’S Effects On Healthspan And The Physiological Processes Of Aging, Brandon Ashmore

Honors Theses

Advanced glycation end products (AGEs) are protein, lipid, or nucleotide molecules that have been combined with sugars through nonenzymatic, irreversible glycation and oxidation reactions. Their accumulation in the body has been associated with the natural aging process and a wide range of pathologies, including chronic inflammation, sustained oxidative stress, diabetes, neurodegenerative diseases, atherosclerosis, and cancer. Their interaction with the receptor for advanced glycation end products (RAGE) has been linked to several proinflammatory signaling pathways associated with neurotoxicity and vascular lesions. While some research has been done on the possible health benefits of RAGE inhibition to extend lifespan, our study hopes …

Synaptic Transmission At The Photoreceptor Ribbon Synapse, Chris Mesnard

Theses & Dissertations

Synaptic transmission relies on the Ca²⁺-dependent release of neurotransmitters packaged into synaptic vesicles. Ribbon synapses have the capability to release multiple vesicles at a time in a highly coordinated and synchronized manner. Glutamate release from rod and cone photoreceptor cells involves presynaptic ribbons composed largely of the protein RIBEYE. To examine roles of ribbons in rods and cones, we studied mice in which GCamP3 replaced the B-domain of RIBEYE. We discovered that ribbons were absent from rods and cones of both knock-in mice possessing GCamP3 and conditional RIBEYE knockout mice. Mice lacking ribbons showed reduced temporal resolution and …

Swallowing Disrupts Tongue-Jaw Coordination During Chewing In A Rat Model Of Parkinson's Disease, Meejan Palhang, N. Charles, Francois Gould

Rowan-Virtua Research Day

The primary motor symptoms of Parkinson’s disease, including bradykinesia, rigidity, and tremor, are associated with difficulties regulating transitions between motor behaviors due to basal ganglia dysfunction. Chewing and swallowing, which are disordered in most patients with Parkinson’s disease, are two complex motor behaviors which overlap in time and share some neuromuscular components. The objective of this study is to identify how Parkinson’s disease affects the coordination of chewing and swallowing. We hypothesize that as a result of impaired regulation of shift between motor patterns, chewing cycles that occur with a swallow will be more affected that chewing cycles occurring in …

Effects Of Acute And Repeated Alcohol Exposure On Expression Of Synaptic-Associated Genes In The Male And Female Mouse Mpfc, Dhruba Podder

Undergraduate Honors Theses

Alcohol use disorder (AUD) is a serious chronic brain disease; in 2021 there were ~29.5 million people in the U.S. diagnosed with AUD. Individuals with AUD often show cognitive impairment such as risky decision-making, difficulties with impulse control, and working memory deficits. This impairment is associated with structural and functional changes in the prefrontal cortex (PFC), an extensively interconnected region of the frontal lobe involved in executive control of goal-directed behaviors. Chronic alcohol exposure in rodents has been seen to cause deficits in performance in behavioral tasks which assess mPFC function such as working memory and behavioral flexibility. It is …

Validating A New In Vivo Model To Study Als, Izabela J. Cimachowska

Student Theses and Dissertations

Buildup of oxidative stress and mitochondrial dysfunction are well known characteristics of both sporadic and hereditary amyotrophic lateral sclerosis (ALS). While both forms of the disease seem to arise from common cellular dysfunction, the genetic disease is studied to a much greater extent. Engineering novel animal models of the sporadic form of the disease is crucial for development of druggable targets to treat ALS and understand the underlying mechanisms. Interestingly, accumulation of oxidative stress by exacerbated emission of reactive oxygen species (ROS) from presynaptic mitochondria is a hallmark of both hereditary and sporadic ALS. Previous work by our laboratory showed …

Perineuronal Nets Are Not Required To Close The Critical Period For Ocular Dominance Plasticity., Emily Crouse

Electronic Theses and Dissertations

In the developing visual system, a transient critical period demarcates when neural circuits are most sensitive to visual experience. In the mouse, the critical period occurs between approximately postnatal day(P) 19 to 32. Closing one eye (monocular deprivation, MD) within the critical period shifts ocular dominance (OD) to be more responsive to the open eye. Nogo-66 Receptor 1 (NGR1) limits OD plasticity to the critical period yet it remains unknown how OD plasticity propagates through primary visual cortex or by which mechanisms NGR1 utilizes to confine said plasticity. In primary studies, NGR1 was selectively deleted in different cortical layers to …

An Investigation Into Structural Plasticity In Peripheral Taste Neurons Associated With Taste Cell Turnover., Zachary Whiddon

Electronic Theses and Dissertations

The continual replacement of taste cells creates interesting questions regarding how the innervating neurons are impacted during this process. Here we ask how innervation within taste buds is affected when taste cell entry is inhibited and reestablished. Inhibition of sonic hedgehog signaling (Shh) is thought to inhibit taste cell turnover. Consistently, fewer new cells were added to individual taste buds after treatment with a Shh-inhibitor compared to vehicle treatment, and taste bud volume decreased after 16 days of treatment. We next examined how taste nerve fiber extension into the gustatory epithelium is affected by preventing taste cell turnover. Ten days …

Synaptic Properties Of Parabigeminal Circuits., Kyle Whyland

Electronic Theses and Dissertations

Subcortical structures of the visual system have been the subject of intense study in recent years, but there remain some important unanswered questions regarding the synaptic relationships linking the nuclei that comprise this important sensory network within the brain. In these studies, we use several modern and traditional approaches, including viral tract tracing, in vitro slice physiology, immunohistochemistry, optogenetics, and electron microscopy to characterize the circuits linking the superior colliculus (SC), parabigeminal nucleus (PBG), and lateral geniculate nucleus (LGN), with particular focus on GABAergic and cholinergic cell types. We found that the SC, an important visuomotor structure with connections to …

Morphological Characterization Of Two Transgenic Strategies For Genetic Access To Semilunar Granule Neurons In The Mouse Dentate Gyrus, David T. Rexford

Masters Theses

Granule cells (GCs) of the dentate gyrus (DG) have been understood as a homogeneous class of neurons exhibiting a characteristic limited firing pattern. A subtype of GC called a semilunar granule cell (SGC) has been identified exhibiting variant morphology, electrophysiology, and positioning from normal GCs. SGCs represent an emerging novel subpopulation of GCs, however, there is presently no genetic tool to access SGCs separately from normal GCs. To provide access for future in vivo studies of this population, we examined two genetic strategies for putative SGC specificity in mouse brain slices. Morphological analysis was performed for quantitative identification of putative …

Role Of Nucleus Accumbens Dopamine Receptor Signaling In The Suppression Of Punished Reward Seeking, Grace M. Joyner, Anna Caroline Toburen

Senior Theses

Previous studies have shown that within the nucleus accumbens (NAc), a brain region associated with motivation and reinforcement learning, activity of neurons expressing the dopamine D2 receptor (D2R neurons) act as a “break” on risky behavior associated with negative outcomes. Moreover, when these neurons are stimulated, rats were found to become more risk averse. However, the impact of dopamine signaling through NAc D2R neurons in risk avoidance is still unclear. To further explore the role of NAc dopamine signaling in punished reward-seeking, we tested rats in a novel punished food-seeking paradigm in which subjects are trained to choose between a …

The Role Of The Kcc2 In Substance Use And Abuse: A Systematic Review [Protocol], Alfred Amendolara, Steven Salazar, Chad Thompson, Hyrum Wright, Andrew Payne

Annual Research Symposium

This poster presents the protocol for an ongoing systematic review investigating the role of potassium chloride co-transporter 2 (KCC2) in substance use, abuse, and addiction.

A Systematic Review: Toxoplasma Gondii Infection And Drugs Of Abuse, Amani Sastry

Annual Research Symposium

No abstract provided.

Appearance Of Two Distinct Clusters Of Glucose Dysregulation In Chronic Intractable Migraine, Roshni Jogin, Kaitlyn Mcfarland, Aparna Naik, Tanner Williford, Matthew Conway, Amar Paul, John A. Kriak, David W. Sant, Kyle B. Bills

Annual Research Symposium

No abstract provided.

Probing Amyloid-Beta Protein Structure And Dynamics With A Selective Antibody, Shikha Grover

Dissertations

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder. The AD brain is characterized by significant neuronal loss and accumulation of insoluble fibrillar amyloid-β protein (Aβ) plaques and tau protein neurofibrillary tangles in the brain. However, over the last decade, many studies have shown that the neurodegenerative effect of Aβ may in fact be caused by various soluble oligomeric forms as opposed to the insoluble fibrils. Furthermore, the data suggest that a pre-fibrillar aggregated form, termed protofibrils, mediates direct neurotoxicity, and triggers a robust neuroinflammatory response.

Antibodies targeting the various conformation of Aβ are important therapeutic agents to prevent the progression …

Characterizing The Roles Of The Variable Linker And Hub Domains In Camkii Activation, Noelle Dziedzic

Doctoral Dissertations

Learning and memory formation at the cellular level involves decoding complex electrochemical signals between nerve cells, or neurons. Understanding these processes at the molecular level requires a comprehensive study of calcium-sensitive proteins that serve as signal mediators within cells. More specifically, the protein calcium/calmodulin-dependent protein kinase II (CaMKII) is a key regulator of downstream cellular signaling events in the brain, playing an important role in long term memory formation. CaMKII is encoded in humans on four different genes: alpha, beta, gamma and delta. For added complexity, each of these gene products can be alternatively spliced and translated into multiple protein …

Antibody-Dependent Enhancement Activity Of A Plant-Made Vaccine Against West Nile Virus, Amber M. Paul, Haiyan Sun, Dhiraj Acharya, Huafang Lai, Junyun He, Fengwei Bai, Qiang Chen

Publications

West Nile virus (WNV) causes annual outbreaks globally and is the leading cause of mosquito-borne disease in Unite States. In the absence of licensed therapeutics, there is an urgent need to develop effective and safe human vaccines against WNV. One of the major safety concerns for WNV vaccine development is the risk of increasing infection by related flaviviruses in vaccinated subjects via antibody-dependent enhancement of infection (ADE). Herein, we report the development of a plant-based vaccine candidate that provides protective immunity against a lethal WNV challenge mice, while minimizes the risk of ADE for infection by Zika (ZIKV) and dengue …

High Volume Multiplex Staining Of Mouse Model In Alzheimer’S Associated Disease Pathology, Chloe Embry

Lewis Honors College Thesis Collection

Although neurodegenerative diseases are often clinically distinct, they typically share common pathological markers. One of the most common causes of clinical dementia is Alzheimer’s disease (AD). Pathologically, AD is defined by the presence of intercellular tangles composed of hyperphosphorylated tau proteins and extracellular plaques made of abnormally cleaved amyloid-beta proteins. However recent genome-wide association studies have also found that many of the predispositions for AD are located on or near genes highly expressed in microglia. In the healthy CNS, microglia act as the brain’s immune system and are chiefly involved in neuronal support and maintaining homeostasis throughout the CNS. Typically, …

Il-1r1 Within The Meningeal Lymphatic System, Nolan Abdelsayed

Lewis Honors College Thesis Collection

The meninges are made up of three membranes; the pia mater, arachnoid mater, and dura mater, that surround the brain and spinal cord. These specialized layers work in concert with cerebrospinal fluid (CSF), to protect the central nervous system by adding a layer of cushion and removing waste products from the CNS. Additionally, the meninges act as a physical barrier between the central nervous system and the periphery. The meningeal lymphatic system is a specialized group of vessels that lie within the meninges that assist in the flow of fluid and waste products from the brain. If the meningeal lymphatic …

Age- And Sex-Dependent Alterations In Primary Somatosensory Neuronal Calcium Network Dynamics During Locomotion, Sami L. Case

Theses and Dissertations--Pharmacology and Nutritional Sciences

Over the past 30 years, the calcium (Ca2+) hypothesis of brain aging has provided clear evidence that hippocampal neuronal Ca2+ dysregulation is a key biomarker of aging. Indeed, age-dependent Ca2+-mediated changes in intrinsic excitability, synaptic plasticity, and activity have helped identify some of the mechanisms engaged in memory and cognitive decline. However, much of this work has been done at the single-cell level, mostly in slice preparations, and in restricted structures of the brain. Recently, our lab identified age- and Ca2+-related neuronal network dysregulation in the cortex of the anesthetized animal. Still, investigations in the awake animal are needed to …

Unraveling The Consequence Of Adult Onset Sulfatide Depletion: Its Implications In Myelin And Axonal Heath In The Context Of Neurodegenerative Disease, Elizabeth Dustin

Theses and Dissertations

Multiple Sclerosis is an immune mediated disease of the CNS. MS is diagnosed through detection of demyelinated regions. However, recent studies demonstrate that Normal Appearing White Matter (NAWM) contains substantial pathology. One such pathology observed in the NAWM is the reduction of sulfatide. The proper stoichiometry of lipids in myelin acts to maintain rapid conduction velocity, provide trophic support to the neuron, and protect the axon from degeneration. We previously characterized a mouse lacking sulfatide’s synthesizing enzyme, CST through constitutive gene disruption and demonstrate that sulfide is required for proper stability of the myelin sheath. However, since MS is typically …

Effects Of Picrotoxin Application On The Cardiac Ganglion Of The American Lobster, Homarus Americanus, John T. Woolley

Honors Projects

Picrotoxin (PTX) has been employed extensively as a tool within the crustacean stomatogastric nervous system (STNS) for its efficacy in blocking K⁺ and Cl⁺ currents gated by both GABA and glutamate. Through blocking some currents in the STNS, PTX allows for examination of other components without their presence. However, effects of PTX are relatively unknown within the lobster’s cardiac ganglion (CG). As an incredibly small nervous system of only nine neurons, the lobster CG presents an excellent model system for studying neural circuits. Given that the chemical synapses in the CG are mediated by glutamate, the present study …

The Role Of Schwann Cells In Nerve Injury: Forskolin-Mediated Camp Activation Upregulates Tnfα Expression Despite Nf-Κb Downregulation In Lps-Treated Schwann Cells, Caitlyn E. Henry, Angela L. Asirvatham Ph.D.

Student Research Poster Presentations 2023

Although Schwann cells are known to play a role in axonal regeneration following nerve injury and inflammation, the exact mechanism is unknown. This study explores two potential mechanisms: the NF-κB and cAMP pathways. The NF-κB pathway produces cytokines, such as TNFα, to regulate inflammation, whereas the cAMP pathway is anti-inflammatory and regulates Schwann cell proliferation via AKAP95 and cyclin D3. Although it is well-known that NF-κB and cAMP are involved in inflammation, not much is known regarding the effects of forskolin-mediated cAMP activation on LPS-mediated NF-κB activation in Schwann cells. In this study, RT4-D6P2T immortalized rat Schwann cells were treated …

The Role Of Serca In Neural Development And Brain Tumors, Hannah M. Christman

Undergraduate Theses, Professional Papers, and Capstone Artifacts

Ion channels are essential for neural function, playing a variety of necessary cellular roles including excitability, maintaining ion gradients, and volume control. While the role of ion channels in neurons is well-defined, much less is known about excitability in neural progenitor cells. Recently it has emerged that these neural precursors may be affected by channelopathies, indicating a critical role of ion channels in neural development. Using the model system Drosophila melanogaster (fruit fly), I investigated the role of the ion channel SERCA (sarco/endoplasmic reticulum Ca2+ATPase). SERCA is a vital calcium ion pump located on the wall of the endoplasmic reticulum, …

Mechanistic Insight Into Traumatic Brain Injury Induced Neuronal Membrane Disruption: Cathepsin B Relocalization And A Neun Negative Cortical Neuron Subpopulation, Martina L. Hernandez

Theses and Dissertations

Traumatic brain injury (TBI) is a mechanical insult to the head that leads to brain damage and, in turn, causes long-term sensory, motor, cognitive, and affective dysfunction. Diffuse pathologies seen following such injury are associated with these life-altering outcomes that impact the daily lives of TBI survivors. The diffuse pathology that this body of work focuses on is neuronal membrane disruption; it is characterized by increased permeability of the neuron’s plasma membrane. Moreover, our lab had previously found that membrane disruption is exacerbated with intracranial pressure (ICP) elevation. We set out to measure the duration of membrane disruption following injury …