Neuroscience and Neurobiology Commons^™

Ganglioside-Cytokine Interaction In The Induction Of Primary Brain Cell Death, John Charles Gorbet

Open Access Theses & Dissertations

Gangliosides have been implicated in multiple pathologies affecting the central nervous system (CNS) and recent research has implicated them in playing an active role in the pathogenesis of multiple sclerosis. Empirical studies and theoretical considerations have suggested the possibility of interactions between gangliosides, like GD3, and pro-inflammatory cytokines present in the nervous system. This study sought to investigate the possibility that either individual gangliosides acting alone or complexed with other species interact with the known immune response factor TNF&alpha to initiate or facilitate cell death in the CNS. I examined the cellular viability and gene expression in primary brain cell …

Preliminary Archaeological Investigations At The Sierra Diablo Cave Site: Paleoindian And Archaic Occupations In Hudspeth County, Texas, Jose Javier Vasquez

Open Access Theses & Dissertations

It is generally rare to find archaeological sites in the Southwest that retain the type of contextual integrity that the Sierra Diablo Cave exhibits. Often times, cave sites such as the one currently studied offer excellent preservation of cultural materials due to the general lack of moisture and isolation from wind and water erosion. The research aimed to determine when the site was occupied as well as the types of activities that were occurring during those occupations. It exhibits an extensive stratigraphic sequence that contains a well pronounced Late Archaic Period assemblage (Strata A and B) and a Late Pleistocene/Early …

Involvement Of The Nmda Receptor In Moderate Ethanol Preconditioning-Dependent Neuroprotection From Amyloid-Beta In Vitro, Robert Matthew Mitchell

Dissertations

Alzheimer's disease (AD) is a progressive, mentally crippling, and eventually fatal form of dementia with growing prevalence in aging populations. In 2009 it was estimated that 5.3 million Americans have AD, with 5.1 million older than age 65 and 200,000 under 65. That accounts for 1 in 8 adults over 65. Furthermore, AD costs Americans 148 billion dollars in direct expenses, and is the leading cause of dementia and the 6th leading cause of death. Since improved medical care in general is increasing average life span and age is the primary risk factor for AD, there is need for basic …

Forced-Exercise Alleviates Neuropathic Pain In Experimental Diabetes: Effects On Voltage-Gated Calcium Channels, Sahadev A. Shankarappa

Dissertations

Exercise is now established as an integral adjunct to the management of diabetes. Diabetic polyneuropathy, a painful complication of diabetes, remains untreatable, emphasizing a critical need for improved therapeutic strategies. Recent evidence suggests that exercise may facilitate recovery of peripheral nerve function in diabetes. However, the mechanism by which exercise protects against diabetes-induced nerve dysfunction is unknown. In this dissertation we hypothesized that forced-exercise protects against experimental DPN by preventing glucose-associated alterations of voltage-gated calcium currents (VGCC) in small diameter dorsal root ganglion (DRG) neurons. Using behavioral, nerve-electrophysiology and patch-clamp methodology we examined the functional consequences of forced-exercise (treadmill, 5.4 …

Hindbrain Serotonin Neurons Activate 5-Ht1a Receptors In The Nucleus Tractus Solitarius (Nts) To Modulate Sympathetic And Ventilatory Recovery Following Hypotensive Hemorrhage, Ling-Hsuan Kung

Dissertations

Trauma is the leading cause of death of young people in the United States. Most such deaths result either from the initial blood loss or from secondary reperfusion injury following resuscitation.

Currently, the standard treatments for hypovolemic shock include volume resuscitation and using of vasoconstrictors to raise pressure. However, these treatments can exacerbate reperfusion injury, and require technical care when apply to patients. Therefore, novel therapies that can safely restore perfusion pressure are needed.

Our lab has found that 5-HT1A-receptor agonist, 8-OH-DPAT, increases perfusion pressure and improves acid-base balance in hypovolemic rats by stimulation of sympathetic-mediated increases in venous tone. …

Mechanisms Of Ipsapirone-Mediated Neuroprotection Of Ethanol-Treated Fetal Rhombencephalic Neurons: Role Of Endogenous Antioxidants, Jongho Lee

Dissertations

Prenatal exposure to ethanol can cause serious damage to the developing central nervous system. Both in vivo and in vitro studies demonstrate the vulnerability of the developing serotonergic system to the damaging effects of ethanol. However, treatment with a serotonin-1A (5-HT1A) agonist prevents the ethanol-associated apoptosis in developing 5-HT neurons. One mechanism by which 5-HT1A agonists exert their neuroprotective effects appears to involve activation of the phosphatidylinositol 3'kinase (PI-3K) pro-survival pathway and activation of NF-κB dependent anti-apoptotic genes. Additional NF-κB dependent genes might also be involved with the neuroprotective effects of ipsapirone.

There is also considerable evidence that ethanol augments …

Metabolic Targeting Of Malignant Glioma: Modulation Of Glycolytic Flux By Erythropoietic Factors, Todd Brendon Francis

Wayne State University Dissertations

Introduction: Malignant glioma display a highly glycolytic phenotype where the tumors flux glucose to lactic acid independent of oxygen concentration ("aerobic glycolysis"). This altered phenotype is facilitated by expression of primarily fetal enzyme isoforms in these malignant tumors. The end-product lactic acid is rapidly expelled from the cytosol by selective monocarboxylate transporters expressed on the plasma membrane. GATA response element islands are present on the promoter of glioma lactate transporter genes, and GATA-1 has been shown to be over-expressed in glioblastoma. Our long-term goal is to inhibit glioma proliferation by indirectly down-regulating GATA-1 to inhibit glycolysis. (Colen et al., 2006; …

Role Of Kappa-Opioid Receptors In The Effects Of Salvinorin A And Ketamine On Attention Behavior In Rats, Christina L. Nemeth, Tracie A. Paine, Joseph E. Rittiner, Cécile Béguin, F. Ivy Carroll, Bryan L. Roth, Bruce M. Cohen, William A. Carlezon Jr.

Faculty & Staff Scholarship

Background: Disruptions in perception and cognition are characteristic of psychiatric conditions such as schizophrenia. Studies of pharmacological agents that alter perception and cognition in humans might provide a better understanding of the brain substrates of these complex processes. One way to study these states in rodents is with tests that require attention and visual perception for correct performance. Methods: We examined the effects of two drugs that cause disruptions in perception and cognition in humans—the kappa-opioid receptor (KOR) agonist salvinorin A (salvA; 0.125–4.0 mg/kg) and the non-competitive NMDA receptor antagonist ketamine (0.63–20 mg/kg)—on behavior in rats using the 5-choice serial …

Mental Reversal Of Imagined Melodies: A Role For The Posterior Parietal Cortex, Robert J. Zatorre, Andrea R. Halpern, Marc Bouffard

Faculty Journal Articles

Two fMRI experiments explored the neural substrates of a musical imagery task that required manipulation of the imagined sounds: temporal reversal of a melody. Musicians were presented with the first few notes of a familiar tune (Experiment 1) or its title (Experiment 2), followed by a string of notes that was either an exact or an inexact reversal. The task was to judge whether the second string was correct or not by mentally reversing all its notes, thus requiring both maintenance and manipulation of the represented string. Both experiments showed considerable activation of the superior parietal lobe (intraparietal sulcus) during …

Perception Of Emotion In Sounded And Imagined Music, Brian L. Lucas, Emery Schubert, Andrea R. Halpern

Faculty Journal Articles

WE STUDIED THE EMOTIONAL RESPONSES BY MUSICIANS to familiar classical music excerpts both when the music was sounded, and when it was imagined.We used continuous response methodology to record response profiles for the dimensions of valence and arousal simultaneously and then on the single dimension of emotionality. The response profiles were compared using cross-correlation analysis, and an analysis of responses to musical feature turning points, which isolate instances of change in musical features thought to influence valence and arousal responses. We found strong similarity between the use of an emotionality arousal scale across the stimuli, regardless of condition (imagined …

Robust Dynamic Balance Of Ap-1 Transcription Factors In A Neuronal Gene Regulatory Network., Gregory M Miller, Babatunde A Ogunnaike, James S Schwaber, Rajanikanth Vadigepalli

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

BACKGROUND: The octapeptide Angiotensin II is a key hormone that acts via its receptor AT1R in the brainstem to modulate the blood pressure control circuits and thus plays a central role in the cardiac and respiratory homeostasis. This modulation occurs via activation of a complex network of signaling proteins and transcription factors, leading to changes in levels of key genes and proteins. AT1R initiated activity in the nucleus tractus solitarius (NTS), which regulates blood pressure, has been the subject of extensive molecular analysis. But the adaptive network interactions in the NTS response to AT1R, plausibly related to the development of …

Synaptic Clustering Of Psd-95 Is Regulated By C-Abl Through Tyrosine Phosphorylation, Karen Perez De Arce, Lorena Varela-Nallar, Olivia Farias, Alejandra Cifuentes, Paulina Bull, Brian A. Couch, Anthony J. Koleske, Nibaldo C. Inestrosa, Alejandra R. Alvarez

School of Biological Sciences: Faculty Publications

The c-Abl tyrosine kinase is present in mouse brain synapses, but its precise synaptic function is unknown. We found that c-Abl levels in the rat hippocampus increase postnatally, with expression peaking at the first postnatal week. In 14 d in vitro hippocampal neuron cultures, c-Abl localizes primarily to the postsynaptic compartment, in which it colocalizes with the postsynaptic scaffold protein postsynaptic density protein-95 (PSD-95) in apposition to presynaptic markers. c-Abl associates with PSD-95, and chemical or genetic inhibition of c-Abl kinase activity reduces PSD-95 tyrosine phosphorylation, leading to reduced PSD-95 clustering and reduced synapses in treated neurons. c-Abl can phosphorylate …

Increased Dendrite Branching In Aβpp/Ps1 Mice And Elongation Of Dendrite Arbors By Fasudil Administration, Brian A. Couch, George J. Demarco, Shannon L. Gourley, Anthony J. Koleske

School of Biological Sciences: Faculty Publications

Amyloid-β (Aβ) overproduction and dendrite arbor atrophy are hallmarks of Alzheimer’s disease. The RhoA GTPase (Rho) signals through Rho kinase (ROCK) to control cytoskeletal dynamics and regulate neuron structure. Hyperactive Rho signaling destabilizes neurons leading to dendritic regression that can be rescued by genetic or pharmacological reduction of ROCK signaling. To understand what effect reduced ROCK signaling has on the dendrite arbors of mice that overproduce Aβ, we administered the ROCK inhibitor fasudil to AβPP/PS1 transgenic mice. We report that increased dendrite branching occurs in AβPP/PS1 mice and that fasudil promotes …

The Abl And Arg Non-Receptor Tyrosine Kinases Regulate Different Zones Of Stress Fiber, Focal Adhesion, And Contractile Network Localization In Spreading Fibroblasts, Justin G. Peacock, Brian A. Couch, Anthony J. Koleske

School of Biological Sciences: Faculty Publications

Directed cell migration requires precise spatial control of F-actin-based leading edge protrusion, focal adhesion (FA) dynamics, and actomyosin contractility. In spreading fibroblasts, the Abl family kinases, Abl and Arg, primarily localize to the nucleus and cell periphery, respectively. Here we provide evidence that Abl and Arg exert different spatial regulation on cellular contractile and adhesive structures. Loss of Abl function reduces FA, F-actin, and phosphorylated myosin light chain (pMLC) staining at the cell periphery, shifting the distribution of these elements more to the center of the cell than in wild-type (WT) and arg^—/— cells. Conversely, loss of Arg function …