Neuroscience and Neurobiology Commons^™

An Analysis Of The Interaction Of Methylphenidate And Nicotine In Adolescent Rats: Effects On Bdnf, Elizabeth D. Freeman

Electronic Theses and Dissertations

This investigation was an analysis of the interaction of adolescent exposure to methylphenidate (MPH; trade name: Ritalin) on nicotine sensitization and conditioned place preference (CPP) in a rodent model and underlying mechanisms of this effect. Animals were treated IP with 1 mg/kg MPH or saline using a ―school day‖ regimen of five days on, two days off, from postnatal day (P) 28-50. During the final two weeks of MPH treatment, animals were either behaviorally sensitized to nicotine (0.5 mg/kg free base) or saline for 10 days, or conditioned to nicotine or saline using the CPP behavioral paradigm. In addition, three …

Glycine Receptor Alpha Subunit (Glyra) Specific Inhibition Contributes To Ganglion Cell Signaling In Mouse Retina., Chi Zhang

Electronic Theses and Dissertations

In the retina, numerous types of neurons are wired together in a highly specific albeit complex pattern. This sophisticated retinal network allows extraction and encoding of more than 20 representations of the visual scene in its output neurons, the retinal ganglion cells (RGCs). Within the inner plexiform layer (IPL) of retina, glycine receptors (GlyRs) are expressed on different cell classes and modulate RGC visual activity to light onset (ON RGCs) and to light offset (OFF RGCs), for example, their temporal precision and gain control. There are four GlyR alpha subunits (GlyRα1-4) with differential expression patterns in IPL. Each mediates spontaneous …

Characterizing The Neuropeptide Pathways Between The Forebrain And The Pons., Ali Al-Magableh

Electronic Theses and Dissertations

Many current health problems including obesity, hypertension, stroke, heart disease, and type 2-diabetes can be attributed to diet. One powerful determinant of food selection is how good or bad a food 'tastes' (e.g. affective value), and is ranked highly by consumers as their top reason for choosing a food (e.g. preference). Learning plays an important role in the establishment and strengthening of food preference and, thus in guiding food choice and calories consumed. The basis of such learning is provided, in part, by limbic system modulation of gustatory neural processing at lower levels in the medulla and pons. I hypothesize …

Move, Interact, And Connect Personally Barter Theatre’S Project Real Gets Implicit In Order To Learn, Megan E. Atkinson

Electronic Theses and Dissertations

Body movement, hands-on activity, embodiment, social interaction, emotions, and self-reflection allow teaching artists of Barter’s Theatre’s Project REAL to conduct a lesson with an implicit learning experience as the focus. Barter Theatre’s Project REAL exists as a theatre for education program that collaborates with regular classroom teachers on delivering the curriculum through specific theatre exercises in order to connect the material personally to the students’ lives. Theatre tools provide a human experience that enhances learning for the student by use of kinesthetic movement, social learning, emotions and interpersonal skills. To understand the effects of Barter Theatre’s Project REAL, the director …

The Effects Of Molecular Chaperones On Tau Fibril Assembly, Ahmed Omran

Electronic Theses and Dissertations

The accumulation of microtubule-associated protein tau into fibrillar aggregates is the hallmark of Alzheimer’s disease and other neurodegenerative disorders, collectively referred to as tauopathies. Fibrils can propagate from one cell to the next and spread throughout the brain. However, a study shows that only small aggregates can be taken up by cultured neuronal cells. The mechanisms that lead to the breakage of fibrils into smaller fragments remain unknown. In yeast, the AAA+ chaperone HSP104 processes the reactivation of protein aggregates and is responsible for fragmentation of fibrils. This study focused on investigating the effects of molecular chaperones on tau fibrils …

Towards Closed-Loop Deep Brain Stimulation: Behavior Recognition From Human Stn, Soroush Niketeghad

Electronic Theses and Dissertations

Deep brain stimulation (DBS) provides significant therapeutic benefit for movement disorders such as Parkinson’s disease (PD). Current DBS devices lack real-time feedback (thus are open loop) and stimulation parameters are adjusted during scheduled visits with a clinician. A closed-loop DBS system may reduce power consumption and side effects by adjusting stimulation parameters based on patient’s behavior. Thus behavior detection is a major step in designing such systems. Various physiological signals can be used to recognize the behaviors. Subthalamic Nucleus (STN) Local field Potential (LFP) is a great candidate signal for the neural feedback, because it can be recorded from the …

The Phenomenon Of Abstract Cognition Among Scholastic Chess Participants: A Case Study, Brent C. Laws

Electronic Theses and Dissertations

A qualitative investigation was conducted to explore the phenomenon of abstract cognition among a purposive sample of 5 secondary scholastic chess club participants. The case study enabled the researcher to explore the faculties of abstract cognition among students of contrasting skills and abilities in playing chess. The study also allowed for the consideration of potential visual-spatial, logical, academic, social competency and life benefits of chess play. Through analysis of interviews, chess simulations, blindfold chess play, and narration of chess lines and sequences, the investigator was able to extract meaning and code schemata into a holistic understanding of the phenomenon of …

Boundary Contour Based Surface Representation., Yong Su

Electronic Theses and Dissertations

We receive most information about our surrounding space and objects through the eyes. To reconstruct the 3D space and objects in the visual system from the 2D retinal images, surface representation must be a critical intermediate stage in the visual processing stream. It is hypothesized in the dissertation that the visual system represents textured surface by a border-to-interior strategy: boundary contours would be encoded first and then border-ownership assignments would be resolved. This process would solve the related problems such as figure-ground segregation, surface depth relationship, occlusion, transparency, etc. As a result, the boundary contours of the surfaces would be …

Cellular-Based Brain Pathology In The Anterior Cingulate Cortex Of Males With Autism Spectrum Disorder, Jessica D. Crawford

Electronic Theses and Dissertations

Autism spectrum disorder (ASD) now affects 1 in 68 children in the United States. Disorders within this spectrum share hallmark deficits in verbal and nonverbal communication, repetitive behavior, and social interaction. The cause of ASD is still unknown. Even though hundreds of genetic abnormalities have been identified in ASD, these markers account for less than 1% of all ASD cases. Researchers continue to search for pathological markers common to all or most cases of ASD. The research presented in this dissertation used a novel combination of state-of-the-art methods to investigate brain pathology in ASD. Postmortem anterior cingulate cortex (ACC) from …

A Comprehensive Study Of The Effects Of Neurotoxins On Noradrenergic Phenotypes, Neuronal Responses And Potential Intervention By Antidepressants In Noradrenergic Cells, Yan Wang

Electronic Theses and Dissertations

It has been reported that locus coeruleus (LC) degeneration precedes the degeneration of other neurons in the brain in some neurodegenerative diseases like Alzheimer’s disease (AD) and Parkinson’s disease (PD). However, the precise mechanisms of neurodegeneration remain to be elucidated. N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP4) has been widely used as a noradrenergic neurotoxin in the development of AD and PD animal models for specific LC degeneration. However, the precise mechanism of action of DSP4 remains unclear. An increased systemic DNA damage caused by neurotoxin or oxidative stress has been found to be related to the pathogenic development of neurodegeneration. The process of neurodegeneration …

Functional Implications Of Demyelination And The Molecular Control Of Remyelination In The Adult Mouse., Nicholas John Kuypers

Electronic Theses and Dissertations

Oligodendrocyte (OL) loss contributes to the functional deficits underlying diseases with a demyelinating component (Gajjar et al., 1997; Miller et al., 2002). Remyelination can restore these deficits (Duncan et al., 2009). Chapter 1 is an introduction to de- and re-myelination thus providing the necessary background information for consideration in subsequent chapters. Ethidium bromide (EB) has been extensively used in the rat and cat as a model of spinal cord demyelination. However, this lesion has not been addressed in the adult mouse. Therefore, Chapters 2 and 3 characterize a model of chronic EB-induced spinal cord demyelination in the mouse which can …

Rho Gtpases In Neuronal Apoptosis And Neurodegeneration, Trisha Stankiewicz

Electronic Theses and Dissertations

Several studies have identified Rho family GTPases (i.e. Rho, Rac, Cdc42) as mediators of diverse critical cellular processes, such as actin cytoskeleton remodeling, gene transcription, cell-cell adhesion, and cell cycle progression. However, more recent data highlight an essential role for Rho GTPases as regulators of neuronal morphology and neuronal survival. In particular, Rac GTPase generally induces neurite outgrowth and promotes neuronal survival while Rho GTPase typically provokes neurite retraction and induces neuronal apoptosis. However, the precise signaling pathways that regulate neuronal survival downstream of Rho GTPases and the potential involvement of dysregulated activity of Rho GTPases as a causative factor …

Amyotrophic Lateral Sclerosis: Mechanism Behind Mutant Sod Toxicity And Improving Current Therapeutic Strategies, Cassandra Dennys

Electronic Theses and Dissertations

Amyotrophic Lateral Sclerosis (ALS) is an always lethal motor neuron disease with unknown pathogenesis. Inhibitors of the molecular chaperone heat shock protein 90 (Hsp90) have limited neuroprotection in some models of motor neuron degeneration. However the direct effect of Hsp90 inhibition on motor neurons is unknown. Here we show that Hsp90 inhibition induced motor neuron death through activation of the P2X7 receptor. Motor neuron death required phosphatase and tensein homolog (PTEN)-mediated inhibition of the PI3K/AKT pathway leading to Fas receptor activation and caspase dependent death. The relevance of Hsp90 for motor neuron survival was investigated in mutant Cu/Zn superoxide dismutase …

Seeded Propagation Of Tau Fibrils, Paul David Dinkel

Electronic Theses and Dissertations

In various neurodegenerative diseases, including Alzheimer's disease, progressive supranuclear palsy, Pick's disease, and corticobasal degeneration, the deposition of fibrils composed of misfolded tau protein is observed. Recent evidence suggests that tau fibrils transfer between cells and spread throughout the brain, underscoring the significance of fibril propagation.

Six tau isoforms exist in the adult human brain that can be grouped into 4-repeat (4R) tau and 3-repeat (3R) tau based on the presence or absence of the second of four microtubule binding repeats. We demonstrate in vitro that seeded fibril growth, a prerequisite for the spreading of the tau pathology, is crucially …

Connexin-32 And Connexin-43 Immunoreactivity In Rodent Taste Buds, Amanda E. Bond

Electronic Theses and Dissertations

Studies indicate that ATP is one of the primary neurotransmitters in taste transduction. ATP release occurs from taste cells via specific hemichannels such as pannexin/connexin hemichannels (Huang et al., 2007; Romanov et al., 2007). We hypothesize that Type II (receptor) and possibly Type III (presynaptic) cells release ATP at sites containing pannexin/connexin hemichannels. In this study, we examine the presence of connexin–32–LIR (Like Immunoreactivity) and connexin–43–LIR in rodent taste buds through immunocytochemical analysis and DAB (Di–amino–benzidine) immunoelectron microscopy. We observed that connexin–32–LIR co–localizes with P2X2–LIR in nerve fibers and in a small subset of NCAM–LIR cells. Connexin–32–LIR does not co–localize …

Nutraceutical Antioxidants And Their Therapeutic Potential In Neurodegeneration, Erika Kristine Ross

Electronic Theses and Dissertations

Amyotrophic lateral sclerosis (ALS) is a fatal neuromuscular disease that affects motor neurons of the brain and spinal cord. Many studies indicate that mitochondrial oxidative stress (MOS) is a principal mechanism underlying the pathophysiology of this and other devastating neurodegenerative diseases. Here, we investigated a unique whey protein supplement (Immunocal®) to determine its neuroprotective efficacy in several in vitro models of MOS and in an in vivo mouse model of ALS. This non-denatured whey supplement contains cystine which is an oxidized form of cysteine, an essential precursor for synthesis of the endogenous antioxidant, glutathione (GSH). In primary cultured rat cerebellar …

Micrornas 9a, 9b, 9c And 315 Regulate Expression Of A Reporter For The Neuronal Microtubule-Associated Protein Futsch/Map1b, Leslie M. Rozeboom

Electronic Theses and Dissertations

Fragile X syndrome (FXS) is the most common form of inherited mental retardation in humans. FXS is caused by loss of the Fragile X Mental Retardation Protein (FMRP), an important regulator of neuronal mRNA translation. Patients with FXS display cognitive deficits including memory problems. Protein synthesis-dependent long-term changes in synaptic plasticity are involved in the establishment and maintenance of long-term memory. One prevalent theory of FXS pathology predicts that FMRP is required to negatively regulate the translation of important mRNAs at the synapse. We are investigating microRNAs (miRNAs) as a potential regulator of synaptic FMRP-regulated mRNAs that have previously been …

Acute Synaptic Activity Causes Differential Mirna Expression In The Drosophila Melanogaster Larval Central Nervous System, Robert Ian Sand

Electronic Theses and Dissertations

The primary goal of this thesis was to determine if spaced synaptic stimulation induced the differential expression of microRNAs (miRNAs) in the Drosophila melanogaster central nervous system (CNS). Prior to attaining this goal, we needed to identify and validate a spaced stimulation paradigm that could induce the formation of new synaptic growth at a model synapse, the larval neuromuscular junction (NMJ). Both Channelrhodopsin- and high potassium-based stimulation paradigms adapted from (Ataman, et al. 2008) were tested. Once validation of these paradigms was complete, we sought to characterize the miRNA expression profile of the larval CNS by miRNA array. Following attainment …

Neurochemical Levels Correlate With Population Level Differences In Social Structure And Individual Behavior In The Polyphenic Spider, Anelosimus Studiosus., Jennifer Bryson Price

Electronic Theses and Dissertations

Anelosimus studiosus is a socially polyphenic spider. Individuals can be classified as social/tolerant or solitary/aggressive. These behavioral differences are associated with considerable variation in social structure. Here, we begin to examine the physiological differences that may underlie the behavioral dimorphism in this species and possible implications for the evolution of sociality. Octopamine is a neurotransmitter that has been found to elevate aggression in invertebrates. Serotonin has been shown, in some cases, to interact antagonistically with octopamine. We used High Pressure Liquid Chromatography with Electrochemical Detection to quantify levels of these neurochemicals among adult females from social (multi-female) and solitary (single-female) …

Overexpression Of Amyloid Precursor Protein Induces Mitochondrial Oxidative Stress And Activates The Intrinsic Apoptosis Pathway, Matthew G. Bartley

Electronic Theses and Dissertations

Down syndrome (DS) is the most common genetic form of cognitive disability and is caused by trisomy of chromosome 21. Within chromosome 21 is the gene, amyloid precursor protein (APP). Proteolysis of APP into toxic and aggregate-prone, beta-amyloid fragments underlies the pathophysiology of Alzheimer's disease (AD). Individuals with DS develop the neuropathology that can be diagnosed as AD; however, the role of APP overexpression in this comorbidity is presently unclear. Here, we elucidated the mechanism of cell death induced by overexpression of wild type APP. Chinese hamster ovary cells transfected with a DsRed-APP fusion construct displayed caspase-3 activation and nuclear …

Neuroprotective Effects Of Anthocyanins On Neuronal Death Induced By Inhibition Of Bcl-2 And Oxidative Stress, Natalie A. Kelsey

Electronic Theses and Dissertations

Neurodegenerative diseases such as Parkinson’s and amyotrophic lateral sclerosis have devastating consequences to the afflicted patients. A major cellular pathophysiology underlying these diseases is mitochondrial oxidative stress (MOS) leading to neuronal death. Here, we investigated the neuroprotective effects of a novel class of nutraceuticals, anthocyanins, against MOS-induced death in primary cultures of rat cerebellar granule neurons (CGNs). Anthocyanins are natural antioxidants whose neuroprotective potential has yet to be examined in detail. Kuromanin and callistephin are anthocyanins derived from black rice and strawberries, respectively. Glutathione (GSH)-sensitive MOS and intrinsic apoptosis were induced in CGNs by the Bcl-2 inhibitor, HA14-1. Callistephin and …

Dopamine D2 Receptor Priming Enhances Dopaminergic Response To Amphetamine In The Nucleus Accumbens: Role Of The D1 And D2 Receptors., Kimberly Norris Huggins

Electronic Theses and Dissertations

In past work, we have shown neonatal quinpirole (dopamine D₂/D₃ agonist) treatment produces a significant increase in dopamine D₂ receptor sensitivity, a phenomenon known as D₂ receptor priming. Dopamine D₂ receptor priming is common in psychosis. Male and female rats were administered quinpirole (1mg/kg) or saline from postnatal days 1-11 and raised to adulthood (P60). As adults, rats were administered d-amphetamine sulfate (1mg/kg) or saline every other day for 14 days. Approximately 10 min before each amphetamine or saline injection, animals were administered the D1 antagonist SCH 23390 (0.1 mg/kg), the D2 antagonist eticlopride …

Mcp-1 And App Involvement Of Glial Differentiation And Migration Of Neuroprogenitor Cells, Emmanuel Vrotsos

Electronic Theses and Dissertations

Neuroprogenitor cells are an important resource because of their potential to replace damaged cells in the brain caused by trauma and disease. It is of great importance to better understand which factors influence the differentiation and migration of these cells. Previously it has been reported that neuroprogenitor cells undergoing apoptotic stress have increased levels of Amyloid precursor protein (APP) and increased APP expression results in glial differentiation. APP activity was also shown to be required for staurosporine induced glial differentiation of neuroprogenitor cells. Monocyte chemoattractant protein-1 (MCP-1) is a chemokine that is expressed during inflammatory. The binding of MCP-1 to …

Elucidating The Role Of The Α7 Nicotinic Receptor In The Etiology Of Schizophrenia., Michelle Johnson Chandley

Electronic Theses and Dissertations

The α7 subunit of the nicotinic receptor, a ligand gated ion channel with an affinity for nicotine, has long been implicated in the pathophysiology of schizophrenia due to the extremely high rate of smoking within the patient population. However, the exact role of the receptor has never fully been determined. In the following studies, various functions the receptor may assume in disease state are evaluated. There is a strong relationship between the immune system and schizophrenia, with the α7 subunit possibly serving as the link between the two. One of the following studies looks at the possibility of the receptor …

Amphetamine Sensitization And In Vivo Microdialysis Of The Nucleus Accumbens Core Of Adult Male And Female Rats D2-Primed As Neonates., Zackary Adam Cope

Electronic Theses and Dissertations

Neonatal administration of quinpirole produces significant increases in D₂ receptor sensitivity that persists into adulthood. This phenomenon, known as D₂ receptor priming, is consistent with pathology in schizophrenia. Rats were administered quinpirole or saline postnatally and raised to adulthood. In adulthood, rats were administered d-amphetamine sulfate or saline every other day and were placed in a locomotor arena where activity was measured over 7 trials. Results showed that D₂-primed rats receiving amphetamine were higher in locomotor activity across all days of testing compared to other groups. This effect was more prominent in males than in females. …

The Endocytic Protein Numb Regulates App Metabolism And Notch Signaling: Implications For Alzheimer's Disease, George Kyriazis

Electronic Theses and Dissertations

Increased production of amyloid beta (A-beta) peptide, via altered proteolytic cleavage of amyloid protein precursor (APP), and abnormalities in neuronal calcium homeostasis play central roles in the pathogenesis of Alzheimer's disease (AD). Notch1, a membrane receptor that controls cell fate decisions during development of the nervous system, has been linked to AD because it is a substrate for the gamma-secretase protein complex in which mutations cause early-onset inherited AD. Numb is an evolutionarily conserved endocytic adapter involved in the internalization of transmembrane receptors. Mammals produce four Numb isoforms that differ in two functional domains, a phosphotyrosine-binding domain (PTB) and a …

Gene Therapy And Cellular Transplantation : Towards A Combination Strategy For Spinal Cord Injury Repair., Ahmed Abdelzaher Abdellatif

Electronic Theses and Dissertations

The combination of viral mediated gene delivery, tissue engineering, and Schwann cell (SC) transplantation offer a promising strategy to enhance axonal regeneration and functional recovery following spinal cord injury (SCI). The rationale and feasibility of using such combination has been extensively reviewed in Chapter 1. The study presented in Chapter 2 showed that lentiviral vectors are most suitable in situations where stable long term transgene expression is needed, while adenovirus and retrovirus are more suited for transient gene delivery. Tissue engineering combined with Schwann cell (SC) transplantation is a promising method to enhance regeneration and remyelination of axons following a …

Nicotine Sensitization In Β-Arrestin 2 Knockout Adolescent Mice., Jennifer A. Correll

Electronic Theses and Dissertations

ß arrestin-2 is a protein involved in signaling of D2 receptors and plays a mediating role in sensitization to psychostimulants and the opiate morphine. In this study, 3-4 week old BA-2 KO and wild type C57/B6 mice received nicotine tartarate (s.c, 0.5 mg/kg free base) for 7 or 14 consecutive days followed by a drug-free period. An acute nicotine challenge followed the drugfree period. Results indicated that the absence of ß-arrestin-2 reduced sensitization to nicotine in Experiment 1. BA-2 KOs eventually demonstrated sensitization in Experiment 2. However, absence of ß-arrestin-2 blocked expression of sensitization on the challenge. After the challenge, …

Glutamate Excitotoxicity In Epilepsy And Ischemia, Mangala Meenakshi Soundarapandian

Electronic Theses and Dissertations

'Excitotoxicity' represents the excitatory amino acid mediated degeneration of neurons. Glutamate is the major excitatory neurotransmitter in the brain. Glutamate excitotoxicity has been implicated in a number of neurodegenerative disorders like Stroke, Epilepsy, Alzheimer's disease and traumatic brain injury. This neurotoxicity is summed up by the 'glutamate hypothesis' which describes the cause of neuronal cell death as an excessive release of glutamate causing over excitation of the glutamate receptors and subsequent increase in influx of calcium leading to cell death. An effort to counteract this neurotoxicity has lead to the development of glutamate receptor antagonists that can effectively serve as …

Previous Spatial Memory Training And Nicotine Administration Alleviates Cognitive Deficits Produced By Medial Frontal Cortex Lesions In Rats., Rachel L. Norris

Electronic Theses and Dissertations

Rats were administered nicotine (0.3 mg/kg) for 11 consecutive days before and after an electrolytic medial frontal cortex lesion. Behavioral testing was arranged so that the rats were tested on the RAM 1 day after drug administration followed by behavioral testing on the MWT 19 days after drug treatment, or tested on the MWT 1 day after drug administration followed by testing on the RAM4 days after drug treatment. Results of MWT testing showed that regardless of the drug/behavioral testing interval, lesioned rats given nicotine demonstrated enhancement relative to saline-treated animals. Results of RAM testing showed that nicotine improved performance …