Medicine and Health Sciences Commons^™

Using Functionalized Benzylidene Oxindoles To Determine An Improved Monoamine Oxidase-B Inhibitor As A Therapeutic Agent For Parkinson's Disease, Christine Morgan Kinstedt

Browse all Theses and Dissertations

With the intent to create an optimized monoamine oxidase-B (MAO-B) inhibitor, researchers in this investigation synthesized derivatives of the benzylidene oxindole scaffold in order to determine a lead molecule for further drug development. Previous work in this laboratory group evaluated a similar scaffold, the chalcone structural unit. As this class of compounds was determined to possess the ability to permeate the blood brain barrier (BBB) and to act as potent MAO-B inhibitors, it was posited that scaffold hopping from this previously studied molecular skeleton to benzylidene oxindoles would provide analogous results. Benzylidene oxindoles are readily synthesized via the Claisen-Schmidt condensation …

Using Fmri Bold Imaging To Motion-Correct Associated, Simultaneously Imaged Pet Data, Joseph M. Williamitis

Browse all Theses and Dissertations

Because magnetic resonance (MR) and positron emission tomography (PET) scanning sessions last long durations, motion blur during scanning constitutes a problem for clinical interpretation. To counteract this, motion-correction algorithms have been developed to reduce smearing between scan slices of MRI, but these algorithms are not commonplace for PET. This feasibility study determined if applying MRI motion-correction algorithms to simultaneously acquired PET data improved PET signal clarity in specific brain regions. Seven subjects received increasing levels of PET tracers while undergoing two separate simultaneous PET/MRI scans. We modified existing fMRI algorithms to apply them to the accompanying PET data. We hypothesized …

The Effect Of Endogenous Ligands Of The Aryl Hydrocarbon Receptor On Antibody Expression In A Human B-Cell Model, Valerie Benedict

Browse all Theses and Dissertations

Small changes in antibody expression have broad impacts on human health and disease. An environmental toxicant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) induces profound immune suppression in animal models in an aryl hydrocarbon receptor (AhR)-mediated fashion. In a human Burkitt's lymphoma cell line (CL-01), TCDD inhibited IgG secretion and differentially impacted Ig heavy chain expression. In addition to TCDD, the AhR has several endogenous, dietary, and bacterial ligands such as 6-formylindolo[3,2-b]carbazole (FICZ) and indole, which are present within the human body at varied concentrations (0.30 mM- 6.64 mM). Both FICZ (100 nM) and indole (100 µM) significantly reduced IgG secretion. Overall antibody secretion is …

Characterization Of B3galt2 And Heg1 Expression In Dorsal Root Ganglia, Alexander H. Nguyen

Browse all Theses and Dissertations

Proprioception provides unique sensory feedback about the body’s orientation in space and this sensation is essential for creating specific motor functions and coordinated movement. During neurogenesis, unique genetic markers are expressed and classified as early, transient/middle, and late markers depending on their timing of expression. This study focuses on the expression patterns of two late markers: Heg1 and B3galt2. We investigated how expression of these two markers respond to peripheral nerve injury (PNI). We cloned and generated riboprobes to detect expression of B3galt2 and Heg1 in DRGs using in situ hybridization after transection of the sciatic nerve. B3galt2 hybridization in …

Connectivity Of Monosynaptic Ia Afferents On Renshaw Cells In Neonatal Mice, Todd Joseph Rapetti

Browse all Theses and Dissertations

Proprioception allows sensory information about muscle position and length to enter the CNS without the aid of visual cues. One type of fiber that carries this information is the Ia afferent, which innervates muscle spindles that respond to mechanical perturbation in muscle. Ia fibers are known to synapse with Ia interneurons (INs) and motor neurons (MNs), setting up important circuits which affect movement. Another type of IN is the Renshaw cell (RC), which is located in the ventral part of lamina VII of the spinal cord and is critical for the functionality of the recurrent inhibitory circuit. In addition to …

The Inhibitory Effects Of Opioids On Voltage-Gated Calcium Influx In Neonatal Rat Carotid Body Type I Cells, Ellen M. Ricker

Browse all Theses and Dissertations

It is known that opioids inhibit the hypoxic ventilatory response, but little is known about the mechanisms that underpin this. This study's objectives were to examine which opioid receptors are located on the oxygen-sensing carotid body type I cells and determine whether selective agonists inhibit cellular excitability.

Immunocytochemistry revealed the presence of μ and κ opioid receptors on type I cells. The μ-selective agonist DAMGO (10μM) and the κ-selective agonist U50-488 (10μM) significantly (p<0.0025 and p<0.0095 respectively, unpaired student's t-test) inhibited high K+ induced rises in intracellular Ca2+ compared with controls. After a three-hour incubation with pertussis toxin, a Gi protein-coupled inhibitor, DAMGO and U50-488 (10μM) has no significant effect on the responses to K+.

These results indicate that opioids acting at μ and κ receptors inhibit voltage-gated Ca2+ influx in carotid body type I cells. This mechanism may explain, in …

Angiotensin-Ii Receptor Blocker And Its Effects On Depressive-Like Behavior During Maternal Separation, Evan D. Xanthos

Browse all Theses and Dissertations

Maternal separation has been shown to promote the onset of adult depression. This early life stressor produces a biphasic response marked by an active "protest" phase followed by a passive "despair" phase in humans and other species. In infant guinea pigs, active phase behaviors include increased locomotion and distress vocalizations, whereas the passive phase is marked by depressive-like behaviors including a crouch stance, eye closure and piloerection. Separation elicits physiological responses including increased core body temperature and proinflammatory cytokine expression suggesting fever. Angiotensin-II receptor blockers (ARB's) inhibit inflammation both peripherally and centrally following peripheral administration. The goal of the present …

Is Polyvinylidene Diflouride (Pvdf) Film Biocompatible In The Murine Cochlea?, Robert Maxwell Jaggers

Browse all Theses and Dissertations

Polyvinylidene fluoride (PVDF) film, a biomaterial that is an integral part of a Totally Implantable Sustainable Hearing Aide (TISHA) device, was examined to determine its biocompatibility within the murine cochlea. The biofilm was implanted in the ear using a round window cochleostomy in 7-9 week old male C57BL/6 mice. Three test groups containing seven mice each were implanted with PVDF film. Each mouse received a sham surgery on the non-implanted cochlea. Three test groups were examined at 48 hours, 3 weeks, and 3 months. At the end of this time the mouse was euthanized, the tissue containing the cochlea was …

Efficacy Of Mastery-Based And Autonomy-Supportive Neuroanatomy Curriculum In Graduate Level Human Neurobiology Course, Corin Wolfgang Magee

Browse all Theses and Dissertations

Anatomy provides scientists with a common vocabulary for discussing the human body, and is, therefore, an important aspect of science education. Literature shows that traditional teaching methods may be enhanced by the employment of mastery-based learning in an autonomy-supportive environment. The present study sought to determine the effects of these teaching strategies on the learning of neuroanatomy in a graduate neurobiology course.

These results show students learned and reportedly enjoyed learning a large amount of neuroanatomy. Experimentally taught students who completed the curriculum did well on the 30-item neuroanatomy quiz (mean score 81%), which was administered at the end of …

Mechanisms Of Hyperglycemia-Induced Ros Production In Osmotically Swollen Glial Cells, Augusta K. Eduafo

Browse all Theses and Dissertations

Cerebral edema is a potentially fatal complication of diabetes. There is evidence for increased Reactive Oxidative Species (ROS) production during cerebral edema in diabetics. This can lead to oxidative stress, thought to contribute to the onset and progression of diabetes and can cause cell injury and cell death. ROS, in moderate amounts, are involved in physiological processes within the body that produce favorable cellular responses. Unfortunately, high levels of ROS can lead to cellular damage of lipids, membranes, proteins and DNA. Hyperglycemia can cause an increase in ROS production due to activation of NADPH oxidases. The purpose of this study …

Effects Of Delayed Pharmacological Treatment And Limb Rehabilitation On Infarct Size And Functional Recovery After Stroke, Maria Helen Harley Balch

Browse all Theses and Dissertations

Previous studies show a fluoxetine/simvastatin drug combination successfully reduced infarct size and increased functional recovery when administered 20-26 hours post stroke. This project tested the hypothesis that earlier drug delivery at 6-12 hours post stroke will improve functional recovery and decrease infarct size, and that limb rehabilitation will improve functional recovery.

Pre-stroke function was determined in rats, a stroke was induced, and daily treatment began 6-12 hours post stroke. Baseline functional deficit was established, and additional testing over 90 days monitored functional recovery. Limb rehabilitation was provided for designated animals, and brain analysis measured infarct size.

In animals with no …

Effect Of Rat Strain Stereotactic Coordinates On Infarct Volume, Saagar K. Sanghvi

Browse all Theses and Dissertations

Ischemic stroke makes up 87% of all hospital-admitted stroke cases annually; the primary treatment for these cases is intravenous administration of tPA within a 3.5 hour window from stroke onset. A long-term delayed ischemic stroke treatment proposed by this study was a combination of the pharmaceuticals Fluoxetine (SSRI), Simvastatin (statin), and ascorbic acid (Vitamin C). 51 adult rat subjects (10-12 months of age; 44 Sprague Dawley, 7 Long Evans) were given a combination of the drugs for 31 days. Drugs were given through voluntary oral administration via sugar cookie-dough balls to reduce inhibition of neurogenesis through stress-related glucocorticoid production. Drug …

Characterization Of Stimulation-Induced Volume Changes In The Ca1 Region Of Rat Hippocampus Slices, Amanda Brooke Gutwein

Browse all Theses and Dissertations

Intrinsic optical signals (IOS) were used to evaluate volume regulation mechanisms during Schaffer collateral stimulation-induced volume changes in hippocampal slices. The effects of stimulation frequency, synaptic function, ionotropic glutamate receptor (iGluR) activation, glutamate uptake, and volume regulatory anion channels (VRAC) were examined with IOS. Data were analyzed using ANOVA with Dunnett's post hoc test (p<0.05 indicated significance). IOS changes were stimulation frequency dependent between 1 Hz and 10 Hz with full recovery of IOS within 5 min. Synaptic blockage reduced the rate of swelling by 81% compared to the control and the IOS did not fully recover. Recovery rate was reduced with iGluR inhibition. Inhibition of glutamate uptake reduced the rate of swelling by 70% compared to vehicle controls. During stimulation, action potentials, iGluR activation, and glutamate uptake contribute to swelling. Regulatory volume mechanisms during stimulation were glutamate-mediated via iGluRs and VRAC independent.

C-Bouton Coverage Of Alpha-Motoneurons Following Peripheral Nerve Injury, Esra Salah Shermadou

Browse all Theses and Dissertations

Peripheral nerve injuries (PNI) cause alternations in central synapses leading to loss of function. The C-bouton synapses onto a-motoneurons in the ventral horn, and has a role in regulating motor output. Following tibial nerve ligation, the somatic C-bouton coverage is depleted (Alvarez et al., 2011), however, it is unknown what happens following crush type injuries. PNI causes neuroglia activation and proliferation that contribute to synaptic alterations, a response that has not been well-characterized in the ventral horn, where motoneurons are located. Therefore, I hypothesize that glia activation following peripheral nerve injury correlates to the degree of depletion of synaptic coverage …

The Role Of Corticotropin-Releasing Factor In The Behavior And Proinflammatory Activity Of Separated Guinea Pig Pups, Vincent Rasahd Alexander

Browse all Theses and Dissertations

Isolation of guinea pig pups in a novel environment first produces active behaviors such as vocalizing and movement; over time, these behaviors wane and pups show characteristic passive responses similar to those produced by increased proinflammatory activity. Further, isolation of pups on two consecutive days has recently been shown to enhance those passive responses on the second day. Endogenous proinflammatory activity is thought to mediate the enhancement (sensitization). An injection of corticotropin-releasing factor (CRF) has been shown to increase passive behavior, possibly by increasing proinflammatory activity. The present study further investigated the role of CRF on proinflammatory activity and behavior …

Maturation Of The Carotid Body Oxygen-Sensor During Rat Development, Julia Paulet

Browse all Theses and Dissertations

Carotid bodies (CB) are paired, oxygen-sensing organs located in the bifurcation of the carotid artery that act as peripheral chemoreceptors in the detection of hypoxic, hypercapnic and acidotic levels in the arterial blood. CBs respond to these fluctuations in blood gases by initiating firing of the carotid sinus nerve. This ultimately results in the appropriate ventilatory change to restore blood gases to their physiological levels. Studies have shown that the hypoxic response of the carotid body in juvenile mammals is low, but as maturation occurs this response is strengthened and clearly exhibited in adults. One theory suggests mitochondria play a …

Effects Of Elevated Glucocorticoid Levels On Dentate Gyrus Development, Zachary Dale Vallandingham

Browse all Theses and Dissertations

Exogenous glucocorticoids are commonly used in modern medications and animal studies examining the effects of glucocorticoids on the developing brain report inconsistent results. Recent reports have questioned the reliability of available drug delivery methods in mice (Herrmann et al., 2009). In our laboratory, variable behavioral results using trace eyeblink conditioning (EBC) suggest that we may be having similar problems delivering glucoroticoids to developing rat pups (Claflin et al., 2005, 2011). Subcutaneous pellets and osmotic minipumps resulted in impaired learning during trace eyeblink conditioning whereas subcutaneous injection of corticosterone (CORT) resulted in facilitation of learning on the same task. One of …

Electrical Brain Stimulation And Depressive-Like Behavior In Guinea Pigs, Nadia Kardegar

Browse all Theses and Dissertations

Maternal separation in guinea pigs produces a biphasic response consisting of an active behavior phase (vocalizations and locomotor activity) followed by a phase of passive depressive-like behavior (crouched stance, piloerection, and eye closure). The mechanism for the transition from the active to the passive phase is unknown. One suggestion is that continual activity of neural circuitry producing active behavior eventually leads to the expression of passive behaviors. The purpose of this study was to test this possibility. Guinea pigs were assigned to experimental and control groups. The experimental group received daily stimulation of the bed nucleus stria terminalis (BNST) to …

Glutamate Receptor-Mediated Taurine Release From The Hippocampus During Oxidative Stress, Brian Christopher Tucker

Browse all Theses and Dissertations

Oxidative stress is an important result of cerebral ischemia and has been directly linked to hippocampal swelling and cytotoxic brain edema in vitro. Swollen brain cells activate volume regulatory mechanisms including a significant efflux of the endogenous sulfonic amino acid taurine via volume-regulated anion channels (VRACs). Studies in brain slice preparations also suggest that the excitatory amino acid glutamate plays an important role in both brain tissue swelling and in cell volume regulation. We examined relationships between oxidative stress, glutamate receptor activation, cell swelling, and volume regulation in acutely prepared slices of rat hippocampus. Our results indicate that the release …

Influence Of Daily Electrical Stimulation Of Periaqueductal Grey On Vocalization And Depressive-Like Behavior During Separation In Guinea Pigs, Jennifer Dazey

Browse all Theses and Dissertations

Maternal separation has been shown to promote the onset of depression. This early life stressor produces a biphasic response marked by an active "protest" phase followed by a passive "despair" phase in humans as well as several other species. In infant guinea pigs, active phase behaviors include increased locomotion and species-typical distress vocalizations, whereas the passive phase is marked by depressive-like behaviors including a crouched stance, eye-closure and extensive piloerection. The mechanism underlying the transition from one phase to the next is still unknown. The purpose of this study was to determine if daily stimulation of the neural pathway initiating …

Persisiting Sensitization Of Depressive-Like Behavior And Thermogenic Response During Maternal Separation In Pre- And Post Weaning Guinea Pigs, Randi Lynn Schneider

Browse all Theses and Dissertations

Early attachment disruption is thought to promote later onset of depressive illness through a process involving sensitization. Maternal separation in guinea pig pups (~21 days of age) produces depressive-like behavior and core body temperature fluctuations that appear to be mediated by proinflammatory activity. These responses are enhanced during repeated separations over several days. Here, enhanced depressive-like behavior and core body temperature responses were observed from the early pre-weaning to the periadolescent period (~10-40 days of age) and persisted for more than a week. The greatest temperature response was observed during the final separation. These results demonstrate persisting sensitization of behavioral …

Aquaporin 4 Expression And Distribution During Osmotic Brain Edema And Following Chronic Treatment Of Desipramine, Sergei Alexander Robinson

Browse all Theses and Dissertations

Osmotic brain edema or chronic treatment with desipramine alters brain water permeability. In this study we investigated aquaporin 4 expression and distribution in these two conditions. Brain edema development was induced by intraperitoneal water injection. Blood serum osmolality decreased from 296 ± 1 mOsm to 278 ± 2 mOsm within 15 min. Cerebral cortex water content increased from 79.8 ± 0.2 % to 81.3 ± 0.5% during 120 min of this hyposmotic exposure. Aquaporin 4 immunostaining intensity at the astrocytic endfeet increased in water injected animals from 2.6 ± 0.04 intensity unites (IU) to 3.2 ± 0.21 IU, while total …

The Role Of Apoptosis In Hela Cells Expressing Hiv-1 Rev, Elizabeth Page

Browse all Theses and Dissertations

The HIV protein Rev is a nucleolar protein that regulates late gene expression in infected cells by promoting the export of under-spliced viral RNAs (Pollard and Malim, 1998). Its over-expression can also inhibit progression through mitosis (Miyazaki et al., 1995), possibly through its ability to depolymerize microtubules (Watts et al., 2000). Consequently, Rev may activate the spindle assembly checkpoint in mitotic cells and increase the frequency of apoptosis. Rev also binds the nucleolar protein B23 involved in ribosome maturation and centrosome duplication. Because loss of B23 function stimulates apoptosis (Ahn et al., 2005), Rev expression may promote apoptosis by inhibiting …

Sensitization Of Behavioral Response To Maternal Separation: Persistence Of The Effect And Role Of Proinflammatory Activity, Jessie Caraway

Browse all Theses and Dissertations

Maternal separation in guinea pigs produces a biphasic response consisting of an active behavior phase followed by a phase of passive behavior (crouched stance, piloerection, and eye closure). Previous studies suggest that pro-inflammatory cytokines mediate passive behavior during the passive phase. It is also known that guinea pig pups separated on two consecutive days show a significant increase (sensitization) in full passive behavior on the second day. The current study examined the persistence and role of pro-inflammatory activity in the sensitization of passive behavior in maternally separated guinea pigs. Guinea pig pups were assigned to one of four groups differing …

Presynaptic Regulation Of Carotid Body Type I Cells By Histaminergic And Muscarinic Receptors, Carrie Marie Thompson

Browse all Theses and Dissertations

Type I cells are one of two main cell types located within the carotid body. These cells respond to hypoxia, hypercapnia, and acidosis by releasing excitatory and inhibitory neurotransmitters. This causes increased firing of the carotid sinus nerve and restores blood gas levels to their physiological values. While previous studies have shown whether individual neurotransmitters are excitatory or inhibitory, this work demonstrates how the interplay between two neurotransmitters may potentially shape the output of the carotid body. Histamine, which has previously been shown to have no effect on intracellular Ca2+ in type I cells, may function to modulate the actions …

Short-Term Administration Of Corticosterone Has Lasting Effects On Learning In Young Rats, Christine L. Wentworth-Eidsaune

Browse all Theses and Dissertations

Corticosterone is a glucocorticoid released as part of the body's response to stress and is known to affect cognitive function, presumably via effects on the hippocampus. Trace classical eyeblink conditioning depends on the hippocampus, and has been used to examine the development of learning processes in young organisms. Experiment 1 was a dosing study, in which time course of effect of corticosterone was followed in 15-day-old Long-Evans rat pups over 24 hours for 4 different concentrations (high: 0.02 mg/g body weight (b.w.), medium: 0.01mg/g b.w., low: 0.005 mg/g b.w. and a vehicle control). In Experiment 2, two subcutaneous injections (0.02 …

Developmental Expression Of Calcium Buffering Proteins In Central Auditory Pathways Of Normal Hearing And Congenitally Deaf Mice, Adam S. Deardorff

Browse all Theses and Dissertations

These experiments analyze differences in synaptic development in central auditory pathways between normal hearing (CBA/J) and congenitally deaf (dn/dn) mice, which provide valuable insight into central synaptic plasticity corresponding to human congenital deafness. Immunofluorescent analysis of the developmental expression of the calcium buffering proteins calretinin, calbindin d-28k, and parvalbumin at various postnatal time points was performed to assess the effects of altered neural activity on the level and/or pattern of protein expression within these nuclei. Results indicate that the pattern of calbindin and parvalbumin is unaffected by congenital deafness in dn/dn mice. However, the pattern of calretinin expression in the …

Inhibition Of Pro-Inflammatory Processes Reduces Sensitization Of The Behavioral Response To Maternal Separation, Kristopher Doojin Paik

Browse all Theses and Dissertations

The current study examined the behavioral sensitization of guinea pig pups in response to consecutive days of maternal separation. In the first experiment, guinea pigs that received centrally administered artificial cerebrospinal fluid or IL-10 exhibited sensitization of passive behaviors from Day 1 to Day 2. IL-10 decreased the levels of passive behaviors on Day 1, as well as the increase on Day 2. The second experiment used unoperated pups, which also showed sensitization of the passive response from Day 1 to Day 2, though the effect appeared reduced relative to control pups of Experiment 1. Collectively, this investigation confirms previous …

Reorganization Of Ia Afferent Synapses On Motoneurons After Peripheral Nerve Injuries, Haley E. Titus

Browse all Theses and Dissertations

After peripheral nerve injuries patients lose and do not recover the stretch reflex which leads to altered locomotor function. The focus of this thesis is to investigate the structural integrity of the central connection between Ia afferents and alpha motoneurons that mediate the stretch reflex. The overall hypothesis is that the density and distribution of Ia synapses on motoneurons is altered after peripheral nerve injuries. Analysis of Ia afferent-motoneuron contacts, revealed by vesicular glutamate transporter 1 (VGLUT1) immunoreactivity, on the soma and dendritic arbor of motoneurons after peripheral nerve injuries revealed major reorganizations in the distribution and density of Ia …

The Presynaptic Regulation Of Isolated Neonatal Rat Carotid Body Type I Cells By Histamine, Drew C. Burlon

Browse all Theses and Dissertations

It has been previously shown that Carotid Body Type I cells have the ability to synthesize, package and release histamine in response to hypoxia, thereby contributing to the modulation of respiration within the rat. Here, isolated neonatal rat carotid body type I cells were used to identify the presynaptic effects of histamine and the specific receptor subtypes that modulate them. Although all four histamine receptor subtypes are expressed on the type I cells, and preliminary data showed promising results, further data proved that the activation of these receptors with histamine or selective agonists caused no rise in intracellular calcium ([Ca2+]i) …