Neuroscience and Neurobiology Commons^™

The Relationship Between Sleep, Working Memory, And Decision Making In Young And Old Adult Populations, Melissa G. Merz

Honors Undergraduate Theses

Sleep is known to influence basic tasks concerning working memory, reaction time and executive functioning (Silva, Wang, Ronda, Wyatt, & Duffy, 2010; Nebes, Buysse, Halligan, Houck, & Monk, 2009). However, the amount that sleep influences these functions varies from study to study possibly due to differences in age and task design. Aim 1A of this study is to determine if sleep quality affects working memory. Aim 1B of this study is to determine if age affects sleep quality and working memory in comparison of young and old adult populations. Finally, Aim 2 of this study is to determine if there …

Transposon-Mediated Stable Suppression Of Gene Expression In The Developing Chick Retina, Masaru Nakamoto, Chizu Nakamoto

Biology Faculty Publications

The embryonic chick has long been a favorite model system for in vivo studies of vertebrate development. However, a major technical limitation of the chick embryo has been the lack of efficient loss-of-function approaches for analyses of gene functions. Here, we describe a methodology in which a transgene encoding artificial microRNA sequences is introduced into embryonic chick retinal cells by in ovo electroporation and integrated into the genome using the Tol2 transposon system. We show that this methodology can induce potent and stable suppression of gene expression. This technique therefore provides a rapid and robust loss-of-function approach for studies of …

Aβ Vaccination In Combination With Behavioral Enrichment In Aged Beagles: Effects On Cognition, Aβ, And Microhemorrhages, Paulina R. Davis, Ginevra Giannini, Karin Rudolph, Nathaniel Calloway, Christopher M. Royer, Tina L. Beckett, M. Paul Murphy, Frederick Bresch, Dieter Pagani, Thomas Platt, Xiaohong Wang, Amy Skinner Donovan, Tiffany L. Sudduth, Wenjie Lou, Erin L. Abner, Richard J. Kryscio, Donna M. Wilcock, Edward G. Barrett, Elizabeth Head

Sanders-Brown Center on Aging Faculty Publications

Beta-amyloid (Aβ) immunotherapy is a promising intervention to slow Alzheimer’s disease (AD). Aging dogs naturally accumulate Aβ and show cognitive decline. An active vaccine against fibrillar Aβ 1–42 (VAC) in aged beagles resulted in maintenance but not improvement of cognition along with reduced brain Aβ. Behavioral enrichment (ENR) led to cognitive benefits but no reduction in Aβ. We hypothesized cognitive outcomes could be improved by combining VAC with ENR in aged dogs. Aged dogs (11–12 years) were placed into 4 groups: (1) control/control (C/C); (2) control/VAC (C/V); (3) ENR/control (E/C); (4) ENR and VAC (E/V) and treated for 20 months. …

The Application Of Half-Life In Clinical Decision Making: Comparison Of The Pharmacokinetics Of Extended-Release Topiramate (Usl255) And Immediate-Release Topiramate, Barry E. Gidal, Annie M. Clark, Bob Anders, Frank Gilliam

Neuroscience Faculty Publications

Objective: For extended-release drugs with multi-compartment kinetics, such as topiramate, effective half-life (t_1/2eff) may be a more clinically relevant parameter than elimination half-life (t_1/2z). Using topiramate as a real-life example, the objective was to compare these half-life values for immediate- and extended-release topiramate (TPM-IR and USL255, respectively) to understand how drug pharmacokinetics may impact drug dosing recommendations.

Methods: The t_1/2z and t_1/2eff for USL255 and TPM-IR were compared using data from a phase I study (N = 36) of 200 mg USL255 administered once daily (QD) or TPM-IR twice daily (BID); effect of sampling duration …

Cx43 Expression Increases In Response To Increased Temperature Incubation In The Developing Chicken Embryonic Brain, Erick A. Barrios

Browse all Theses and Dissertations

We used the chicken embryo model to examine whether altered incubation temperature during chicken embryo development would alter the protein expression of heat shock protein 70 (hsp70), hsp90, and connexin 43 (cx43) in the brain. We incubated eggs in either optimal (37.6° C, Con), increased (39.6° C, +2), or decreased (35.6° C, -2) temperature conditions until they reached embryonic day 16 (E16). The -2 condition significantly increased incidence of embryonic mortality. As shown in the literature, the development of the eggs was accelerated or decelerated due to increased or decreased temperature respectively. To control for this, we incubated eggs at …

4-Nonylphenol Induces Neurodegeneration By Altering Cytoskeleton, Cynthia Carreon

Open Access Theses & Dissertations

4-nonylphenol (4-NP), an endocrine-disrupting compound (EDC), has been shown to affect brain development and may cause neurodegeneration. In the environment, 4-NP arises as a degradation product of alkylphenol polyethoxylates, compounds widely used as nonionic surfactants in commercial production, as well as in herbicides, pesticides, polystyrene plastics, and paints and has been shown to undergo a high level of accumulation in biological tissues. However, the mechanism by which 4-NP exerts its effect is not understood. Recent results from our laboratory indicate that Gβγ, an important component of the G protein-signaling pathway, induces neuronal outgrowth and differentiation by modulating microtubule (MT) assembly, …

Metabolic And Morphologic Shifts In Neuro2a Cells Cultured In Galactose Medium, Leah Welker

Masters Theses

It has been observed that highly-proliferating cells, such as cancer cells, rely mainly on glycolysis for ATP production, regardless of presence of oxygen. This effect, however, can be reversed by changing the main energy substrate in the medium from glucose to galactose. The oxidation of galactose in glycolysis yields less net ATP, presumably forcing the cell into OXPHOS. This has been established in many cell lines, including HeLA, HepG2, and skeletal muscle cells. As of yet, this has not been reproduced in neuronal cells. Using Neuro2a, a murine neuroblastoma cell line, this study exposes neuronal cells to galactose medium, and …

Effects Of Asiatic Acid On Neurite Outgrowth In Neuro-2a Cells, Aishah Asiri

Masters Theses

Recently, medicinal plants from ancient Ayurvedic medicine have provided clues to the discovery of novel therapeutics for various diseases. In Ayurvedic medicine, a common Indian plant, Centella asiatica is highly regarded as a "rasayana" or nerve tonic. The Centella extract is used to ward off age-related dementia and to increase memory and intelligence. The mechanism by which Centella improves memory and learning and reduces the risk of dementia is unclear.

We recently tested the effects of asiatic acid, the main active component of Centella, on neuronal growth. We hypothesized that asiatic acid will promote neuronal growth and neurite network …

Stretch Activated Channels In Proprioceptive Organs Of Crab And Crayfish Are Sensitive To Gadolinium But Not Amiloride, Ruthenium Red Or Low Ph, Viresh Dayaram, Cole A. Malloy, Sarah Martha, Brenda Alvarez, Ikenna Chukwudolue, Nadera Dabbain, Dlovan D.Mahmood, Slavina Goleva, Tori Hickey, Angel Ho, Molly King, Paige Kington, Matthew Mattingly, Samuel Potter, Landon Simpson, Amanda Spence, Henry Uradu, Jacob Van Doorn, Robin L. Cooper

Biology Faculty Publications

The type of stretch activated receptors (SARs) in the chordotonal organs in the crab walking leg and of the muscle receptor organ (MRO) in the crayfish abdomen have not yet been classified as to their molecular or pharmacological profile. The purpose of this study is to examine the pharmacological profile of SARs in the proprioceptive neurons in the crab and crayfish models. Since many SARs share the pharmacological profile of displaying low pH or being proton sensitive (i.e. being more active) or blocked by the diuretic amiloride or ruthenium red as well as being blocked by the broad stretch activated …

Developmental Toxicity Of Nicotine: A Transdisciplinary Synthesis And Implications For Emerging Tobacco Products, Lucinda J. Enland, Kjersti Aagaard, Michele Bloch, Kevin Conway, Kelly Cosgrove, Rachel Grana, Thomas J. Gould, Dorothy Hatsukami, Frances Jensen, Denise Kandel, Bruce Lanphear, Frances Leslie, James R. Pauly, Jenae Neiderhiser, Mark Rubinstein, Theodore A. Slotkin, Eliot Spindel, Laura Stroud, Lauren Wakschlag

Pharmaceutical Sciences Faculty Publications

While the health risks associated with adult cigarette smoking have been well described, effects of nicotine exposure during periods of developmental vulnerability are often overlooked. Using MEDLINE and PubMed literature searches, books, reports and expert opinion, a transdisciplinary group of scientists reviewed human and animal research on the health effects of exposure to nicotine during pregnancy and adolescence. A synthesis of this research supports that nicotine contributes critically to adverse effects of gestational tobacco exposure, including reduced pulmonary function, auditory processing defects, impaired infant cardiorespiratory function, and may contribute to cognitive and behavioral deficits in later life. Nicotine exposure during …

Widespread Tau Seeding Activity At Early Braak Stages, Jennifer L. Furman, Jaime Vaquer-Alicea, Charles L. White, Nigel J. Cairns, Peter T. Nelson, Marc I. Diamond

Pathology and Laboratory Medicine Faculty Publications

Transcellular propagation of tau aggregates may underlie the progression of pathology in Alzheimer's disease (AD) and other tauopathies. Braak staging (B1, B2, B3) is based on phospho-tau accumulation within connected brain regions: entorhinal cortex (B1); hippocampus/limbic system (B2); and frontal and parietal lobes (B3). We previously developed a specific and sensitive assay that uses flow cytometry to quantify tissue seeding activity based on fluorescence resonance energy transfer (FRET) in cells that stably express tau reporter proteins. In a tauopathy mouse model, we have detected seeding activity far in advance of histopathological changes. It remains unknown whether individuals with AD also …

A Laser-Pulse Photolysis Study Of The Mechanism Of Potentiation Of The Glua2qflip Ampa Receptors By Cx546, Yu-Chuan Shen

Legacy Theses & Dissertations (2009 - 2024)

Insufficient activity of the α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-type glutamate ion channels is involved in neurological disorders and developmental problems, such as schizophrenia, one of the most serious psychiatric diseases. Use of regulatory agents to enhance AMPA receptor activity under the circumstance has been shown therapeutically beneficial. Specifically, small-molecule compounds generally termed as potentiators or positive modulators of AMPA receptors have long been pursued as drug candidates for a potential treatment of these neurological disorders and diseases. The goal of my MS thesis work is to investigate the mechanism of potentiation on AMPA receptor by a classic potentiator known as CX546. The …

Elucidating The Transcriptional Regulation Underlying Neural Induction, Sarah E. Hirsch

Legacy Theses & Dissertations (2009 - 2024)

The brain is one of the most complicated structures in the human body and its development is also elusive. Great strides have been made in expounding some of the complex mechanisms of neural development, which allows for the creation of innovative, less invasive, and more effective treatments for neurodevelopmental and neurodegenerative disorders. The advent of stem cell technology has brought therapy development for these disorders closer to a reality, as stem cells provide a platform to model early stages of human neural development. This is of great importance, as only through studying neurodevelopment will the various transcriptional and molecular components …

Disease In A Dish : Modeling Tau Pathology For Future Antibody Testing, Leneea Toyisha Warner

Legacy Theses & Dissertations (2009 - 2024)

ABSTRACT

Analysis Of Candidate Genes For Seizure Susceptibility In Epileptogenesis, Brittany O'Brien

Legacy Theses & Dissertations (2009 - 2024)

The occurrence of recurrent spontaneous seizures is the hallmark of epilepsy. The key to understanding how a normal brain can develop epilepsy through a process known as epileptogenesis is identifying susceptibility factors. Previously, various strains of inbred mice from the hybrid mouse diversity panel were subjected to multiple seizures via the repeated flurothyl model (RFM) for epileptogenesis. The results demonstrated differences in kindling among the inbred strains; specifically two main trends in the generalized seizure threshold (GST) data were kindling-sensitive and kindling-resistant strains. In addition, genome wide association studies done from these mice demonstrated a quantitative trait locus (QTL) on …

Retinal Disease Modeling And Drug Screening Using Stem Cell Derived Retinal Pigment Epithelium, Janmeet Singh Saini

Legacy Theses & Dissertations (2009 - 2024)

The eye is an intricate organ, possessing sensory receptors in the retina that are involved in visual perception. The retina consists primarily of the neural layer, referred to as the neural retina, and the pigmented layer, referred to as the retinal pigment epithelium (RPE). The neural retina and RPE develop and mature in a coordinated manner, and depend on each other for survival. In a mature healthy retina, the retinal photoreceptor outer segments interdigitate with the RPE monolayer, and they co-exchange key supportive factors. RPE cells are indispensable for the health of the retina as they are involved in a …

Harnessing Electrocorticographic Signals For Neuroscience And Neurosurgery, Adriana De Pesters

Legacy Theses & Dissertations (2009 - 2024)

Daily human activities, such as speaking, driving or listening to music, are produced by activations of neurons in the brain. Where, when and how these activations occur has been the subject of intense debate for the last decades. Traditional techniques to image the human brain, such as functional magnetic resonance imaging (fMRI) or electroencephalography (EEG), only provide limited information regarding where and when these activations take place. For that reason, critical information is currently missing regarding how neurons from different parts of the brain interact and coordinate their activity to implement behavior. This information is critical to understand human behavior …

The Neonatal Anti-Viral Response Fails To Control Measles Virus Spread In Neurons Despite Interferon-Gamma Expression And A Th1-Like Cytokine Profile, Priya Ganesan

Electronic Theses and Dissertations

Neonates are highly susceptible to infections in the central nervous system (CNS) and have a greater risk of viral infections and encephalopathies. Neurotropic viral infections can lead to blindness, hearing loss and neurological deficiencies such as cognitive impairment, epilepsy, and even death in the neonatal and pediatric populations. Viral infections also are hypothesized to indirectly contribute to neurodegenerative and neuropsychiatric diseases such as Schizophrenia and Parkinson’s disease later in life due to early neuronal damage or stress. Many diverse viruses are capable of invading the neonatal CNS including Borna Disease Virus, Coxsackievirus (CV), Herpes simplex viruses (HSV), and measles virus. …

Bladder Antimuscarinics And Cognitive Decline In Elderly Patients, Daniela Claudia Moga, Erin L. Abner, Qishan Wu, Gregory A. Jicha

Pharmacy Practice and Science Faculty Publications

Introduction: The evidence on the impact of bladder antimuscarinics initiation on cognitive function in older adults is inconsistent.

Methods: A retrospective analysis of data from the National Alzheimer's Coordinating Center (NACC) on enrollees 65 years and older evaluated the association between antimuscarinic initiation and cognitive decline. We defined decline from baseline (yes/no) for cognitive assessments included in the NACC Uniform Data Set 2.0 battery. New users were matched on year of enrollment and time in the cohort to randomly selected nonusers. Analyses were conducted using inverse probability of treatment weights based on baseline propensity scores.

Results: Our analyses included 698 …

Effects Of Chromium On Mouse Splenic T Lymphocytes And Effects Of Ethanol Exposure During Early Neurodevelopment On Behaviors In Mice, Lu Dai

Theses and Dissertations--Toxicology and Cancer Biology

The dissertation consists of three major projects with the focus on the immunotoxicity of chromium and the behavior disorders caused by early ETOH exposure respectively.

Hexavalent chromium [Cr(VI)] is widely used in various industrial processes and has been recognized as a carcinogen. As the first line of host defense system, the immune system can be a primary target of Cr(VI). T cell population represents a major arm of the immune system that plays a critical role in host anti-tumor immunity. Dysfunction of T cells compromises host anti-tumor immunity resulting in oncogenesis. Using mouse splenic T cells as an in vitro …