Neuroscience and Neurobiology Commons^™

Post-Translational Modification Regulates Heterogeneous Nuclear Ribonucleoprotein K Function During Axon Outgrowth In Xenopus Laevis, Erica J. Hutchins

Legacy Theses & Dissertations (2009 - 2024)

The RNA-binding protein, heterogeneous nuclear ribonucleoprotein K (hnRNP K), is required for axon outgrowth. Its suppression in Xenopus embryos causes defects in the translation of mRNAs of multiple cytoskeletal genes. Studies in cell lines have established that hnRNP K shuttles between the nucleus and the cytoplasm to bind and regulate the fates of its target RNAs, from splicing to export and translation. At each step, hnRNP K is regulated through post-translational modifications that alter its nucleic acid and protein interactions, and subcellular localization. Precisely how this happens in developing neurons to coordinate cytoskeletal gene expression with the extracellular signals directing …

Btbr-Fvb Chromosome 4 Congenic Displays Rescue Of Behavior And Neuro-Anatomical Phenotypes, Jessica F. Gracias

Legacy Theses & Dissertations (2009 - 2024)

Autism is commonly called the most genetic of neuropsychiatric disorders. Currently, the only diagnostic test is a behavioral evaluation performed by trained physicians and psychologists. There is an urgent need for biomarkers to diagnose autism instead of just relying on behavior and there is also a need to understand the basis of this disorder. One of the theories is that malformation of the corpus callosum is one of the factors that lead to the behavior deficits seen in autism. This theory is based on the fact that human MRI studies have shown that the corpus callosum is absent or malformed …

Functional Roles Of The Insulin-Regulated Glucose Transporter-4 In The Hippocampus, Jiah Pearson-Leary

Legacy Theses & Dissertations (2009 - 2024)

Although a great deal of research has elucidated both localization and function of many glucose transporters (GluTs) throughout the brain, the function of brain insulin-responsive glucose transporter-4 (GluT4) remains unclear (McEwen & Reagan, 2004). Because type 2 diabetes mellitus (T2DM; insulin resistance, i.e., impaired insulin signaling) is a risk factor for Alzheimer's disease (AD), and because the signaling mechanisms insulin uses to mediate hippocampal processes and memory are unclear, a major purpose of this dissertation was to determine whether hippocampal GluT4, which is responsible for insulin's glucoregulatory and canonical effects in the periphery, is necessary for insulin's effects in the …

The Role Of Progesterone Receptor In The Development Of The Mesocortical Dopaminergic Pathway, Jari Willing

Legacy Theses & Dissertations (2009 - 2024)

The mesocortical dopaminergic pathway, comprised of projections from the ventral tegmental area (VTA) to the prefrontal cortex (PFC), mediates many of the most complex forms of cognitive behaviors and has been associated with clinical disorders such as ADHD and schizophrenia. While this circuit continues to develop throughout much of the lifespan, there is a rapid period of maturation, early in development, in which this circuit is highly sensitive to disruption. Steroid hormone receptors are powerful transcription factors, capable of affecting a variety of neurodevelopmental processes and are expressed in many regions throughout the developing brain. Specifically, the nuclear progesterone receptor …

Peripheral Nerve Injury Is Associated With Chronic, Reversible Changes In Global Dna Methylation In The Mouse Prefrontal Cortex, Maral Tajerian, Sebastian Alvarado, Magali Millecamps, Pascal Vachon, Cecilia Crosby, M. Catherine Bushnell, Moshe Szyf, Laura S. Stone

Publications and Research

Changes in brain structure and cortical function are associated with many chronic pain conditions including low back pain and fibromyalgia. The magnitude of these changes correlates with the duration and/or the intensity of chronic pain. Most studies report changes in common areas involved in pain modulation, including the prefrontal cortex (PFC), and pain-related pathological changes in the PFC can be reversed with effective treatment. While the mechanisms underlying these changes are unknown, they must be dynamically regulated. Epigenetic modulation of gene expression in response to experience and environment is reversible and dynamic. Epigenetic modulation by DNA methylation is associated with …

Olanzapine Sensitization And Clozapine Tolerance: From Adolescence To Adulthood In The Conditioned Avoidance Response Model, Jing Qiao, Hong Li, Ming Li

Department of Psychology: Faculty Publications

Disruption of conditioned avoidance response (CAR) in rodents is one trademark feature of many antipsychotic drugs. In adult rats, repeated olanzapine (OLZ) treatment causes an enhanced disruption of avoidance response (sensitization), whereas repeated clozapine (CLZ) treatment causes a decreased disruption (tolerance). The present study addressed (1) whether OLZ sensitization and CLZ tolerance can be induced in adolescent rats, and (2) the extent to which OLZ sensitization and CLZ tolerance induced in adolescence persists into adulthood. Male adolescent Sprague–Dawley rats (approximate postnatal days (BP) 43–47) were first treated with OLZ (1.0 or 2.0 mg/kg, subcutaneously (sc)) or CLZ (10 or 20 …

Effects Of Intranasally Administered Dnsp-11 On The Central Dopamine System Of Normal And Parkinsonian Fischer 344 Rats, James H. Sonne

Theses and Dissertations--Neuroscience

Due to the blood-brain barrier, delivery of many drugs to the brain has required intracranial surgery which is prone to complication. Here we show that Dopamine Neuron Stimulating Peptide 11 (DNSP-11), following non-invasive intranasal administration, protects dopaminergic neurons from a lesion model of Parkinson’s disease in the rat. A significant and dose-dependent increase in an index of dopamine turnover (the ratio of DOPAC to dopamine) was observed in the striatum of normal young adult Fischer 344 rats by whole-tissue neurochemistry compared to vehicle administered controls.

Among animals challenged with a moderate, unilateral 6-hydroxy-dopamine (6-OHDA) lesion of the substantia nigra, those …

Post-Traumatic Sleep Following Diffuse Traumatic Brain Injury, Rachel K. Rowe

Theses and Dissertations--Neuroscience

Traumatic brain injury (TBI) is a major cause of death and disability throughout the world with few pharmacological treatments available for individuals who suffer from neurological morbidities associated with TBI. Cellular and molecular pathological processes initiated at the time of injury develop into neurological impairments, with chronic sleep disorders (insomnia, hypersomnolence) being among the somatic, cognitive and emotional neurological impairments. Immediately post-injury, TBI patients report excessive daytime sleepiness, however, discordant opinions suggest that individuals should not be allowed to sleep or should be frequently awoken following brain injury. To provide adequate medical care, it is imperative to understand the role …

Changes In Sleep Architecture And Cognition With Age And Psychosocial Stress: A Study In Fischer 344 Rats, Heather M. Buechel

Theses and Dissertations--Pharmacology and Nutritional Sciences

Changes in both sleep architecture and cognition are common with age. Typically these changes have a negative connotation: sleep fragmentation, insomnia, and deep sleep loss as well as forgetfulness, lack of focus, and even dementia and Alzheimer’s disease. Research has shown that psychosocial stressors, such as isolation from family and friends or loss of a loved one can also have significant negative effects on sleep architecture and cognitive capabilities. This leaves the elderly in a particularly vulnerable situation: suffering from cognitive decline and sleep dysregulation already, and more likely to respond negatively to psychosocial stressors. Taking all of these factors …

Nmda Receptors In The Dorsal Vagal Complex Of Normal And Diabetic Mice, Eva C. Bach

Theses and Dissertations--Physiology

The dorsal vagal complex (DVC), containing the nucleus of the solitary tract (NTS) and the dorsal motor nucleus of the vagus nerve (DMV), plays a pivotal role in autonomic regulation. Afferent fibers from peripheral organs and higher brain centers synapse in the NTS, which integrates these synaptic connections as well as information from systemically circulating hormones and metabolites. The integrated information is relayed to the dorsal motor nucleus of the vagus nerve (DMV), which in turn, projects motor fibers to elicit parasympathetic control of digestive and other viscera. Physiological functions mediated by the DVC are disrupted in diabetic patients and …

Diet-Induced Obesity: Dopaminergic And Behavioral Mechanisms As Outcomes And Predictors, Vidya Narayanaswami

Theses and Dissertations--Pharmacy

Obesity and drug abuse share common neural circuitries including the mesocoticolimbic and striatal dopamine reward system. In the current study, a rat model of diet-induced obesity (DIO) was used to determine striatal dopamine function, impulsivity and motivation as neurobehavioral outcomes and predictors of obesity. For the outcome study, rats were randomly assigned a high-fat (HF) or a low-fat (LF) diet for 8 wk. Following the 8-wk HF-diet exposure, rats were segregated into obesity-prone and obesity-resistant groups based on maximum and minimum body weight gain, respectively, and neurobehavioral outcomes were evaluated. For the predictor study, neurobehavioral antecedents were evaluated prior to …

Manufacturing Nerve Guidance Conduits By Stereolithography For Use In Peripheral Nerve Regeneration, Mireya Aidee Perez

Open Access Theses & Dissertations

Nerve regeneration techniques have been studied in great depth in recent years. Peripheral nerve injuries, in particular, can be caused by accidents, falls, athletic injuries, etc. Current methods of repair include direct suturing of the 2 injured nerve ends or the use of autografts, when a nerve section is taken from another area of the body. Both methods have a series of limitations which have led researchers to study alternative methods of repair. Nerve guidance conduits may provide a viable solution because they can be modified and adapted to the patient's needs. Some conduits already exist on the market and …

A Dna Computer For Glioblastoma Multiforme Diagnosis And Drug Delivery, Sumaiya F. Hashmi

CMC Senior Theses

Glioblastoma multiforme (GBM) is a debilitating malignant brain tumor with expected patient survival of less than a year and limited responsiveness to most treatments, often requiring biopsy for diagnosis and invasive surgery for treatment. We propose a DNA computer system, consisting of input, computation, and output components, for diagnosis and treatment. The input component will detect the presence of three GBM biomarkers: vascular endothelial growth factor (VEGF), caveolin-1α (CAV), and B2 receptors. The computation component will include indicator segments for each of these genes, and ensure that output is only released if all the biomarkers are present. The output component …

Prospective, Open-Label Trial Measuring Satisfaction And Convenience Of Two Formulations Of Lamotrigine In Subjects With Mood Disorders, Martha Sajatovic

Faculty Scholarship

Background: Lamotrigine is an anticonvulsant drug indicated for the maintenance treatment of bipolar I disorder and for various types of epilepsy. An orally disintegrating tablet (ODT) of lamotrigine was developed to provide a formulation option that might increase patient convenience and satisfaction. Methods: Subjects with mood disorders who reported difficulty swallowing currently prescribed lamotrigine immediate-release medication (baseline) were enrolled and treated with lamotrigine ODT for three weeks (end of treatment). Subject satisfaction and convenience were measured using the Treatment Satisfaction Questionnaire for Medication (TSQM). Also measured were global psychopathology using the Clinical Global Impression severity index (CGI-S) and depressive symptoms …

Injury Establishes Constitutive Μ-Opioid Receptor Activity Leading To Lasting Endogenous Analgesia And Dependence, Gregory F. Corder

Theses and Dissertations--Physiology

Injury causes increased pain sensation in humans and animals but the mechanisms underlying the emergence of persistent pathological pain states, which arise in the absence of on-going physical damage, are unclear. Therefore, elucidating the physiological regulation of such intractable pain is of exceptional biomedical importance. It is well known that endogenous activation of µ-opioid receptors (MORs) provides relief from acute pain but the consequences of prolonged endogenous opioidergic signaling have not been considered. Here we test the hypothesis that the intrinsic mechanisms of MOR signaling promote pathological sensitization of pain circuits in the spinal cord. We found that tissue inflammation …

Contributions Of Individual Differences In Stress Reactivitiy To Post-Traumatic Stress Disorder Vulnerability And Resilience, Jonathan Edward Hill

Dissertations (1934 -)

Post-traumatic stress disorder (PTSD), an anxiety disorder precipitated by exposure to extreme emotional and/or physical stress, is characterized by persistent, intrusive memories of the precipitating trauma. Thus, the pathogenesis of PTSD has been conceptualized as involving a deficit in consolidation mechanisms underlying the extinction of fear memory. The mechanisms underlying this deficit have not been elucidated. In addition to intrusive memories, patients with PTSD display heightened sensitivity of the hypothalamic pituitary adrenocortical (HPA) axis to glucocorticoid negative feedback. As glucocorticoids are important modulators of memory consolidation, increased sensitivity to HPA negative feedback, by blunting glucocorticoid responses, may contribute to memory-related …

Examination Of Hippocampal N-Methyl-D-Aspartate Receptors Following Chronic Intermittent Ethanol Exposure In Vitro, Anna R. Reynolds

Theses and Dissertations--Psychology

Chronic intermittent ethanol exposure (CIE) is associated with degeneration of hippocampal neurons. The present study used hippocampal cultures to examine the loss of NeuN immunoreactivity, a relaible marker or neuronal density, after 1, 2, or 3 cycles of 5 days EtOH exposure (50 mM), followed by a 24-hour period of EWD or continuous EtOH exposure. NeuN immunoreactivity was decreased by 13%, 19%, and 16% in the CA1, CA3, and dentate gyrus after 3 cycles of CIE respectively; thionine staining confirmed significant cellular losses within each hippocampal subregion. Two cycles of CIE in aged tissue cultures resulted in significant decreases in …

The Cellular Nucleic Acid Binding Protein In Aging And Disease, Robin Webb

Theses and Dissertations--Molecular and Cellular Biochemistry

The ZNF9 gene on chromosome 3 encodes the cellular nucleic acid binding protein (CNBP), a ubiquitously expressed, 177 amino acid (≈19.5kDa) protein that is highly conserved among vertebrates. The function of the protein is largely unknown, however an expansion in the first intron of the protein results in myotonic dystrophy type 2 (DM2), a multisystemic disease featuring cardiac arrhythmia, muscle wasting, cataracts, and a range of neuropathologies. Remarkably, we recently discovered that CNBP is involved in regulating the activity of β-secretase, the enzyme that produces the first cleavage event in the generation of the amyloid-β peptide (Aβ). The progressive fibrillization …

The Regulation And Packaging Of Synaptic Vesicles Related To Recruitment Within Crayfish And Fruit Fly Neuromuscular Junctions: Variations In Low- And High-Output Terminals, Wenhui Wu

Theses and Dissertations--Biology

Glutamate is the main excitatory neurotransmitter in the CNS and at the neuromuscular junctions (NMJs) of invertebrate. The characteristic similarities to CNS glutamatergic synapses in vertebrate and the anatomical simplicity of invertebrate NMJs favor the investigation of glutamatergic synaptic functions in this system. This dissertation mainly aimed to physiologically separate two functional vesicle groups, the reserve pool (RP) and readily releasable pool (RRP) within presynaptic nerve terminals of Procambarus Clarkii and Drosophila melanogaster. This was addressed in part by blocking the vesicular glutamate transporter (VGlut) with bafilomycin A1. Various frequencies of motor nerve stimulation, exposure time, and concentration of …

Delayed Amyloid Plaque Deposition And Behavioral Deficits In Outcrossed Aβpp/Ps1 Mice, Brian A. Couch, Meghan E. Kerrisk, Adam C. Kaufman, Haakon B. Nygaard, Stephen M. Strittmatter, Anthony J. Koleske

School of Biological Sciences: Faculty Publications

Alzheimer’s disease (AD) is a progressive neurodegenerative dementia characterized by amyloid plaque accumulation, synapse/dendrite loss, and cognitive impairment. Transgenic mice expressing mutant forms of amyloid-β precursor protein (AβPP) and presenilin-1 (PS1) recapitulate several aspects of this disease and provide a useful model system for studying elements of AD progression. AβPP/PS1 mice have been previously shown to exhibit behavioral deficits and amyloid plaque deposition between 4–9 months of age. We crossed AβPP/PS1 animals with mice of a mixed genetic background (C57BL/6 × 129/SvJ) and investigated the development of AD-like features in the resulting outcrossed mice. The onset of memory-based behavioral impairment …