Neuroscience and Neurobiology Commons^™

Melatonin Signaling A Key Regulator Of Glucose Homeostasis And Energy Metabolism, Sharon Owino, Daniella D.C. Buonfiglio, Cynthia Tchio, Gianluca Tosini

Neuroscience: Faculty Publications

Melatonin, a hormone synthesized by both the pineal gland and retina, functions as an important modulator of a number of physiological functions. In addition to its rather well-established roles in the regulation of circadian rhythms, sleep, and reproduction, melatonin has also been identified as an important regulator of glucose metabolism. Recent genomic studies have also shown that disruption of melatonin receptors signaling may contribute to the pathogenesis of type 2 diabetes, although the exact mechanisms underlying its action remain unclear. Additionally, a large number of animal studies have highlighted a role for melatonin in the regulation of both glucose metabolism …

Effect Of Administration Of Somatostatin Analogue On Blood Pressure In Chronic Intermittent Hypoxic Rats, Kajal Kamra

Browse all Theses and Dissertations

The cardiorespiratory system in our bodies does not adapt to Chronic Intermittent Hypoxia (CIH) and consequently syndromes such as sleep apnea lead to pathophysiological conditions like Hypertension. It has been demonstrated that the peripheral chemoreceptors underpin the development of these conditions and at present, there are no selective drug therapies for this form of hypertension. However, evidence suggests that peripheral chemoreflex sensitivity to CO2 & hypoxia is reduced by Somatostatin (SST) in humans. Our preliminary in-vitro studies have demonstrated that SST will blunt the response of the carotid body to hypoxia and decrease the baseline activity of the carotid body. …

Exploring Mechanisms Of Persistent Cognitive Deficits In Mice With Transient Hyperhomocysteinemia, Reeya Khanal

Neuroscience Scholars Theses

Hyperhomocysteinemia (Hhcy) has been found in the elderly and is considered a risk factor for several neurological diseases, especially Alzheimer’s and Vascular Dementia. Previous studies have found an increase in Blood-Brain Barrier (BBB) leakage, glial activation, neuronal damage, and cognitive deficit with elevated levels of plasma homocysteine. Lowering homocysteine could be an easy and inexpensive way to reduce the risk of dementia. But it is still not known for sure if reducing plasma homocysteine levels can recover cognitive function. In our transient Hhcy model, 28 mice were given Hhcy inducing or nutritionally matched control diet for 8 weeks and then …

Dna Methylation Of The Clusterin Promoter: Associations With Alzheimer’S Disease Risk And Related Phenotypes, Madeline Peretti

Theses: Doctorates and Masters

Background

In 2017 approximately 50 million people worldwide were living with dementia. With Alzheimer’s disease (AD), accounting for 50-70% of dementia cases making this debilitating disease, with no current effective prevention, treatment or cure, a critical healthcare concern. Genome wide association studies (GWAS) have identified a number of risk genes for late onset AD (LOAD); Apolipoprotein E (APOE), a gene involved in the cholesterol/lipid pathway is considered the gene with the greatest risk. The third most associated AD risk gene is Clusterin (CLU), is also involved in the cholesterol/lipid pathway. CLU has been implicated in both …

Behavioral And Molecular Analysis Of Memory In The Dwarf Cuttlefish, Jessica M. Bowers

College of Graduate Studies: Theses & Dissertations

Complex memory has evolved because it benefits animals in all areas of life, such as remembering the location of food or conspecifics, and learning to avoid dangerous stimuli. Advances made by studying relatively simple nervous systems, such as those in gastropod mollusks, can now be used to study mechanisms of memory in more complex systems. Cephalopods offer a unique opportunity to study the mechanisms of memory in a complex invertebrates. The dwarf cuttlefish, Sepia bandensis, is a useful memory model because its fast development and small size allows it to be reared and tested in large numbers. However, primary literature …

Pharmacologic Profiling Of Novel Compounds Via Fluorometric Analyses Of Monoamine Transporter Responses, Ashkhan Hojati

Theses and Dissertations

In humans and other organisms, monoaminergic systems are crucial in neuronal function and behavior. The monoamine transporters (MATs), which can be found on the presynaptic plasma membrane of neurons in the central nervous system (CNS), are crucial in the regulation of neurotransmitter concentration in the synaptic cleft. As the duration and concentration of neurotransmitters in the cleft affect further downstream signaling responses, these proteins are important targets for both understanding neuronal physiology and compounds of interest. Multiple theories exist proponing the contribution of MATs to a variety of mental and neurological disorders, including depression. This theory establishes that depression is …

Role Of Glial Ccr5 In Mediating Hiv-1 Tat And Opiate Neurotoxicity And Behavioral Phenotype, Sarah Kim

Theses and Dissertations

Human immunodeficiency virus type 1 (HIV-1) persists in certain CNS cell populations, despite peripheral control of the infection with modern antiretroviral therapy. Infected and/or activated cells release viral proteins, such as trans-activator of transcription (Tat) and various pro-inflammatory factors such as CCL5, creating a positive loop of neuro-inflammation. This serves as the basis for the resulting sublethal and lethal neuropathology that manifests as a spectrum of HIV-mediated CNS impairments, known as HIV-associated neurocognitive disorders (HAND). Opiates, which exist as an interlinked epidemic with HIV-1 infections, exacerbate these neurological effects through direct and indirect mechanisms that disrupt both glial and neuronal …

Glial Cell Mechanisms Regulate Alcohol Sedation In Drosophila Melanogaster, Kristen M. Lee

Theses and Dissertations

Approximately 16 million people in America are diagnosed with Alcohol Use Disorder (AUD) but no efficacious medical treatments exist. Alcohol-related behaviors can be studied in model organisms, and changes in these behaviors can be correlated with either (i) a risk for alcohol dependence or (ii) a symptom/feature of AUD itself. Although AUD is a disease of the central nervous system, a majority of research has focused on the neuronal underpinnings, leaving glial contributions largely undescribed. We used Drosophila melanogaster (fruit fly) to identify genes whose expression in glia regulates alcohol sedation. Mammals and Drosophila have conserved behavioral responses to alcohol …

Examining Police Officer Satisfaction With Mental Health Resources, Jessica Renee Burke

Walden Dissertations and Doctoral Studies

The purpose of this study was to determine the overall satisfaction officers experience with the mental health resources provided by their department. The research aimed to determine whether or not age had an impact on satisfaction levels of police officers. The results from this research would provide information for law enforcement agencies to use in evaluating their own mental health services. Archival survey data from the National Police Suicide Foundation (n = 48) was used for this study to examine the research question: how does age impact an officer's satisfaction in mental health resources. A linear regression was used to …

A Developmental Study Of Apoptotic Markers And Histamine In Cephalopod Statocysts, Samantha Nicole Leef

Honors Theses and Capstones

Cephalopods can participate in complex navigation using landmarks that show context due to their statocysts. Statocysts are analogous to the vertebrate vestibular and auditory system encased in cartilage rather than bone making them more easily accessible. Age and anatomical dysfunctions are the reasons for many human vestibular malfunctions. Two of these sources are endolymph hydrops and aging. In the past, endolymph pressure changes were attributed to the ineffectual ion transport. Recent studies have illuminated the possibility of histamine receptors in the semicircular canal could be responsible for patients’ endolymph pressure changes rather than the previous belief that the pressure changes …

The Role Of Progesterone Receptor In The Developing Medial Preoptic Nucleus, Diana Lalitsasivimol

Legacy Theses & Dissertations (2009 - 2024)

Numerous neurodevelopmental and neuropsychiatric diseases have a distinct sex bias in

The Role Of Progesterone Receptor In The Development Of The Mesocortical Serotonergic Pathway, Allyssa Phillips

Legacy Theses & Dissertations (2009 - 2024)

The mesocortical serotonergic pathway, consisting of serotonergic fibers projecting from the dorsal raphe nucleus (DRN) to the prefrontal cortex (PFC), regulates higher order executive functions and complex cognitive behaviors. Disruptions in this pathway lead to dysfunction in behavior and have been linked to several clinical disorders, including anxiety and ADHD. While this pathway continues to change throughout the lifespan, it is during early development that this pathway undergoes a rapid period of maturation, with the greatest rate of fiber innervation and synaptogenesis occurring in the mesocortical serotonergic pathway at this time. The development of a properly functioning circuit is directed …

Characterization Of A Novel, Stress-Responsive Sexually Dimorphic Corticotropin-Releasing Factor Receptor 1 (Crfr1) Nucleus In The Rostral Anteroventral Periventricular Nucleus Of The Mouse, Zachary Julius Rosinger

Legacy Theses & Dissertations (2009 - 2024)

Within the United States, women are at double the risk of men to develop a stress-related mood disorder (e.g., anxiety or depression) during their reproductive years (Kornstein et al., 2000; Kessler et al., 2005). Many factors contribute to the potential sex difference in such disorders, including gonadal hormones (hypothalamic-pituitary-gonadal axis; HPG) and how they interact with the stress response system, or hypothalamic-pituitary-adrenal (HPA) axis. Corticotropin-releasing factor (CRF) signals through binding the GS-coupled receptor, CRF receptor 1 (CRFR1), and activity between CRF/CRFR1 regulates the hormonal and behavioral stress response (Chen et al., 1993; Bale and Vale, 2004; Heinrichs et al., 1995; …

Developmental Changes In The Activation And Structure Of The Contextual Fear Neural Circuit From Infancy To Adulthood, Anthony John Santarelli

Legacy Theses & Dissertations (2009 - 2024)

The contextual fear circuit, centered on the basolateral nucleus of the amygdala (BLA), is comprised of projections from the hippocampal formation and prefrontal cortex, and mediates an animals ability to learn and predict associations between the environment and biologically relevant stimuli. While the function and structure of this circuit has been well characterized in adult species, relatively little is known about its development as an animal transitions from infancy to adulthood. Recent evidence has begun to suggest that infants, juveniles, and adolescents may show remarkable heterogeneity in the behavioral, activational, and structural properties of the circuit. In this thesis, I …

Uridine Promotes Neurite Outgrowth In Neuro2a Cells, Jacquelyn Spathies

Undergraduate Honors Theses

Neurodegenerative diseases such as Alzheimer's and Parkinson's are the main causes of age-related dementia. These diseases can be due to neuronal cell death and/or impairment of neurite outgrowth. Giant oyster mushroom (GOM), Pleurotus giganteus, is used as a nootropic to improve cognitive function. GOM can also be used to prevent the onset of dementia. The underlying mechanism behind the medicinal property of GOM is unclear. Previous studies have shown that GOM has a high concentration of uridine. In this study, I examined the effects of uridine on neurite outgrowth in the Neuro-2a (N2a) neuroblastoma cell line. We also examined …

Differential Associations Of Distinct Forms Of Childhood Adversity With Neurobehavioral Measures Of Reward Processing: A Developmental Pathway To Depression, Meg J. Dennison, Maya L. Rosen, Kelly A. Sambrook, Jessica L. Jenness, Margaret A. Sheridan, Katie A. Mclaughlin

Neuroscience: Faculty Publications

Childhood adversity is associated with altered reward processing, but little is known about whether this varies across distinct types of adversity. In a sample of 94 children (6–19 years), we investigated whether experiences of material deprivation, emotional deprivation, and trauma have differential associations with reward-related behavior and white matter microstructure in tracts involved in reward processing. Material deprivation (food insecurity), but not emotional deprivation or trauma, was associated with poor reward performance. Adversity-related influences on the integrity of white matter microstructure in frontostriatal tracts varied across childhood adversity types, and reductions in frontostriatal white matter integrity mediated the association of …

Frank Beach Award Winner: Neuroendocrinology Of Group Living, Annaliese K. Beery

Neuroscience: Faculty Publications

Why do members of some species live in groups while others are solitary? Group living (sociality) has often been studied from an evolutionary perspective, but less is known about the neurobiology of affiliation outside the realms of mating and parenting. Colonial species offer a valuable opportunity to study nonsexual affiliative behavior between adult peers. Meadow voles (Microtus pennsylvanicus) display environmentally induced variation in social behavior, maintaining exclusive territories in summer months, but living in social groups in winter. Research on peer relationships in female meadow voles demonstrates that these selective preferences are mediated differently than mate relationships in …

Molecular Mechanism Of Neurodegeneration Induced By 4-Nonylphenol, Michelle Alejandra Aranda

Open Access Theses & Dissertations

Neurodegeneration, a progressive loss of nerve cells, occurs in many neurological disorders, including Alzheimer's disease (AD) and Parkinson's diseases (PD), as well as in dementia. The pathogenesis of these diseases is unknown, and recent evidence suggests that environmental factors, which act as endocrine-disrupting compounds (EDCs) could play a significant role in developing the disease process. 4-Nonylphenol (4-NP), an EDC, and a ubiquitous environmental toxin has been shown to affect brain development and may cause neurodegeneration. 4-NP is produced in large quantities in the U.S. and used as raw materials for making detergents, pesticides, plastics, paints, cosmetics, rubber, and other industrial/household …

Investigating The Role Of Neuronal Aging In Fragile X-Associated Tremor/Ataxia Syndrome, Katlin Marie Hencak

Honors Undergraduate Theses

Fragile X-associated tremor/ataxia syndrome (FXTAS) is an X-linked late-onset neurodegenerative disorder caused by a noncoding trinucleotide repeat expansion in the FMR1 gene. This gene produces fragile x mental retardation protein (FMRP), an RNA binding protein whose targets are involved in brain development and synaptic plasticity. One of the proposed mechanisms of FXTAS pathogenesis is an RNA gain-of-function in which the repeat expansion causes toxic mRNA that sequesters important proteins in the cell, interfering with their functions. Another suggested method of pathogenesis is through a mutant protein called FMRpolyG. This protein results from repeat-associated non-AUG (RAN) translation, in which the expanded …

Molecular Basis Of Membrane Pore Formation By Amyloid Beta Peptide, Nabin Kandel

Electronic Theses and Dissertations

Alzheimer's Disease (AD) is a neurodegenerative disorder that affects around 50 million people worldwide and causes cognitive decline, brain atrophy and death. Despite extensive basic and clinical studies and drug development efforts, currently no effective treatments are available for AD. The amyloid β (Aβ) peptide is neurotoxic and is tightly associated with AD pathology, but the molecular mechanism of its action remains unclear. There are various forms of Aβ in the brain, ranging from the full length Aβ1-42 to shorter peptides, such as a strongly toxic Aβ25-35 fragment. The Amyloid Cascade Hypothesis (ACH) postulated that extracellular Aβ deposits cause the …

Improving Dopamine Monitoring With Ncam And The Effects Of Intranasal Oxytocin On Dopamine Signaling In The Rat Brain, Darren Earl Ginder

EWU Masters Thesis Collection

Dopamine (DA) is a neurohormone highly involved in learning and memory. Oxytocin (OXT), another neurohormone, has also been implicated in learning and memory. Fast-scan cyclic voltammetry (FSCV) is a method used for the real-time examination of DA neurotransmission in the brain. Implanting FSCV electrodes is an invasive technique that likely results in an inflammatory response (i.e. gliosis) that can restrict FSCV recording of DA signals. Neural cell adhesion molecule (NCAM) may reduce gliosis and potentially improve the ability of FSCV electrodes to monitor DA signaling. Chapter 1 Methods: FSCV electrodes were coated with NCAM and implanted in the rat brain. …

Rapid No• Measures In Rat Nucleus Accumbens And Frontal Cortex Following Nasal Administration Of Nitroglycerin, Victoria A. Scott

Theses and Dissertations--Medical Sciences

Nitric Oxide (NO) is a powerful endogenous free radical that has numerous biological functions including vasodilation and serves as a post synaptic second messenger in the central nervous system (CNS). Numerous studies implicate NO• involvement in CNS disorders such as schizophrenia and drug abuse. These studies address the direct in vivo determination of an FDA-approved NO• donor (nitroglycerin) on extracellular levels of NO• in the frontal cortex and core of the nucleus accumbens in a lightly anesthetized rat. State-of-the-art in vivo amperometric recording techniques coupled with a novel 4-channel low noise pre-amplifier system and new generation microelectrode arrays (MEAs) will …

Neuroprotective Strategies Following Experimental Traumatic Brain Injury: Lipid Peroxidation-Derived Aldehyde Scavenging And Inhibition Of Mitochondrial Permeability Transition, Jacqueline Renee Kulbe

Theses and Dissertations--Neuroscience

Traumatic brain injury (TBI) represents a significant health crisis. To date there are no FDA-approved pharmacotherapies available to prevent the neurologic deficits caused by TBI. Following TBI, dysfunctional mitochondria generate reactive oxygen and nitrogen species, initiating lipid peroxidation (LP) and the formation of LP-derived neurotoxic aldehydes, which bind mitochondrial proteins, exacerbating dysfunction and opening of the mitochondrial permeability pore (mPTP), resulting in extrusion of mitochondrial sequestered calcium into the cytosol, and initiating a downstream cascade of calpain activation, spectrin degradation, neurodegeneration and neurologic impairment.

As central mediators of the TBI secondary injury cascade, mitochondria and LP-derived neurotoxic aldehydes make promising …

Autologous Peripheral Nerve Grafts To The Brain For The Treatment Of Parkinson's Disease, Andrew Welleford

Theses and Dissertations--Neuroscience

Parkinson’s disease (PD) is a disorder of the nervous system that causes problems with movement (motor symptoms) as well as other problems such as mood disorders, cognitive changes, sleep disorders, constipation, pain, and other non-motor symptoms. The severity of PD symptoms worsens over time as the disease progresses, and while there are treatments for the motor and some non-motor symptoms there is no known cure for PD. Thus there is a high demand for therapies to slow the progressive neurodegeneration observed in PD. Two clinical trials at the University of Kentucky College of Medicine (NCT02369003, NCT01833364) are currently underway that …

The Role Of Endoplasmic Reticulum Stress In Ethanol-Induced Neurodegeneration, Yongchao Wang

Theses and Dissertations--Pharmacology and Nutritional Sciences

Heavy ethanol use causes neurodegeneration manifested by neuronal loss and dysfunction. It is becoming imperative to delineate the underlying mechanism to promote the treatment of ethanol-induced neurodegeneration. Endoplasmic reticulum (ER) stress is a hallmark and an underlying mechanism of many neurodegenerative diseases. This study aims to investigate the role of ER stress in ethanol-induced neurodegeneration. In experimental design, adult mice were exposed to binge ethanol drinking by daily gavage for 1, 5, or 10 days and the response of ER stress was examined. We found the induction of ER stress appeared at 5 days and remained at 10 days. Moreover, …

Exploring The Role Of Insulin Receptor Signaling In Hippocampal Learning And Memory, Neuronal Calcium Dysregulation, And Glucose Metabolism, Hilaree N. Frazier

Theses and Dissertations--Pharmacology and Nutritional Sciences

In the late 90’s, emerging evidence revealed that the brain is insulin-sensitive, highlighted by broad expression of brain-specific insulin receptors and reports of circulating brain insulin. Contemporary literature robustly supports the role of insulin signaling in normal brain function and suggests that insulin-related processes diminish with aging, evidenced by decreased signaling markers, reduced insulin receptor density, and lower levels of insulin transport across the blood-brain barrier. In the context of pathological cognitive decline, clinical trials using intranasal insulin delivery have reported positive outcomes on memory and learning in patients with mild cognitive decline or early-stage Alzheimer’s disease. However, while the …

Amazon Nights Ii: Electric Boogaloo-Neural Adaptations For Communication In Three Species Of Weakly Electric Fish, Kathryne M. Allen

Graduate Theses, Dissertations, and Problem Reports (ETD)

Sensory systems have to extract useful information from environments awash in noise and confounding input. Studying how salient signals are encoded and filtered from these natural backgrounds is a key problem in neuroscience. Communication is a particularly tractable tool for studying this problem, as it is a ubiquitous task that all organisms must accomplish, easily compared across species, and is of significant ethological relevance. In this chapter I describe the current knowledge of what is both known and still unknown about how sensory systems are adapted for the challenges of encoding conspecific signals, particularly in environments complicated by conspecific-generated noise. …

Aptamer Functionalized Zinc Oxide Field Effect Transistors For Odor Detection, Michael D. Aldridge

Graduate Theses, Dissertations, and Problem Reports (ETD)

Odor detection and identification are complex processes, and tasks that currently only animals do well. There is a pressing need for an electronic nose, or eNose, with good sensitivity, selectivity, and speed that mimics that ability. Food quality control operations, environmental sensing, occupational safety, and the defense sectors all require systems that can rapidly and reliably detect trace levels of volatile organic compounds. The goal of this work is to create a biologically inspired device which can accurately detect and identify odors at concentrations consistent with the most sensitive biological systems.

In order to mimic a natural olfactory system, we …

Identifying Dopamine Receptor Genes And Transcription Marbled Crayfish, Wolfgang Stein, Saisupritha Talasu

Faculty Publications – Biological Sciences

Modulatory transmitters are major contributors to nervous system plasticity and behavioral flexibility, they determine motivational states and are involved in psychiatric and neurological disorders. Neuromodulators act through a variety of distinct receptors and due to the diversity in receptor subtypes and distribution, a single neuromodulator can exert many different actions. A prerequisite to understand the ways modulators work is thus to identify which receptors are expressed in an animal.

I studied which Dopamine receptors are present in the Procambarus virginalis, a highly invasive species of all female genetic clones with high quality genome and transcriptomes. Their broad behavioral repertoire makes …

The Bionic Brain: Pragmatic Neuroethics And The Moral Plausibility Of Cognitive Enhancement, Peter A. Depergola Ii

Philosophy, Theology and Religious Studies Faculty Publications

The seemingly infinite possibilities of contemporary neuroscience span from the augmentation of memory, executive function, appetite, libido, sleep, and mood, to the maturation and development of emotional health and personality. These prospects hint at the capacity to alter neurocognitive conceptions of reality. They also mark the unavoidable inculcation of nuanced individual responses, perhaps radical, to these “tailor- made” perceptions. Hence, there exists certain neuroethical, and even more generally, existential risks within this fascinating and expeditious enterprise. The primary question in the context of present-day neurotechnology is not what can be done, but what should be. To that end, this paper …