Neurosciences Commons^™

Strad Pseudokinases Regulate Axogenesis And Lkb1 Stability, Biliana O. Veleva-Rotse, James L. Smart, Annette F. Baas, Benjamin Edmonds, Zi-Ming Zhao, Allyson Brown, Lillian R. Klug, Kelly Hansen, Gabrielle Rielly, Alexandria P. Gardner, Krishnaveni Subbiah, Eric A. Gaucher, Hans Clevers, Anthony P. Barnes

Faculty Publications - Department of Biological & Molecular Science

No abstract provided.

Ube3a Role In Synaptic Plasticity And Neurodevelopmental Disorders.The Lessons From Angelman Syndrome., Irina Filonova

USF Tampa Graduate Theses and Dissertations

Angelman Syndrome (AS) is a severe neurodevelopmental disorder that affects 1:12000 newborns. It is characterized by mental retardation, delayed major motor and cognitive milestones, seizures, absence of speech and excessive laughter. The majority of AS cases arise from deletions or mutations of UBE3A gene located on the chromosome 15q11-13. UBE3A codes for E3-ubiquitin ligase that target specific proteins for degradation. To date, a wide variety of Ube3a substrates has been identified. The accumulation of Ube3a-dependent proteins and their effect on the multitude of signal transduction pathways are` considered the main cause of the AS pathology. While the majority of research …

Role Of Peripheral Immune Response In Microglia Activation And Regulation Of Brain Chemokine And Proinflammatory Cytokine Responses Induced During Vsv Encephalitis, Christina D. Steel, Kimberly Breving, Susan Tavakoli, Woong-Ki Kim, Larry D. Sanford, Richard P. Ciavarra

Biological Sciences Faculty Publications

We report herein that neuroinvasion by vesicular stomatitis virus (VSV) activates microglia and induces a peripheral dendritic cell (DC)-dependent inflammatory response in the central nervous system (CNS). VSV neuroinvasion rapidly induces multiple brain chemokine and proinflammatory cytokine mRNAs that display bimodal kinetics. Peripheral DC ablation or T cell depletion suppresses the second wave of this response demonstrating that infiltrating T cells are primarily responsible for the bimodal characteristics of this response. The robust infiltrate associated with VSV encephalitis likely depends on sustained production of brain CCL19 and CCR7 expression on infiltrating inflammatory cells. © 2013 Elsevier B.V. All rights reserved.

Direct Control Of Visual Perception With Phase-Specific Modulation Of Posterior Parietal Cortex, Andrew Jaegle, Tony Ro

Publications and Research

We examined the causal relationship between the phase of alpha oscillations (9–12 Hz) and conscious visual perception using rhythmic TMS (rTMS) while simultaneously recording EEG activity. rTMS of posterior parietal cortex at an alpha frequency (10 Hz), but not occipital or sham rTMS, both entrained the phase of subsequent alpha oscillatory activity and produced a phase-dependent change on subsequent visual perception, with lower discrimination accuracy for targets presented at one phase of the alpha oscillatory waveform than for targets presented at the opposite phase. By extrinsically manipulating the phase of alpha before stimulus presentation, we provide direct evidence that the …

Adolescent Crash Rates And School Start Times In Two Central Virginia Counties, 2009-2011: A Follow-Up Study To A Southeastern Virginia Study, 2007-2008, Robert Daniel Vorona, Mariana Szklo-Coxe, Rajan Lamichhane, J. Catesby Ware, Ann Mcnallen, David Leszczyszyn

Community & Environmental Health Faculty Publications

Background and Objective: Early high school start times (EHSST) may lead to sleep loss in adolescents ("teens"), thus resulting in higher crash rates. (Vorona et al., 2011). In this study, we examined two other adjacent Virginia counties for the two years subsequent to the above-mentioned study. We again hypothesized that teens from jurisdictions with EHSST (versus later) experience higher crash rates.

Methods: Virginia Department of Motor Vehicles supplied de-identified aggregate data on weekday crashes and time-of- day for 16-18 year old (teen) and adult drivers for school years 2009-2010 and 2010-2011 in Henrico and Chesterfield Counties (HC and CC, respectively). …

Impact Of Nutrition On Cognition And Its Association With Blood And Brain Alzheimer Disease Related Biomarkers, Samantha Gardener

Theses: Doctorates and Masters

Alzheimer’s disease (AD), the most common form of senile dementia, currently affects over 35 million people worldwide. While there is no cure or effective treatment, early intervention programs hold considerable promise. Following particular dietary patterns represents one potential intervention strategy accessible to all.

Results from previous studies investigating the association of diet, cognition and biomarkers of AD are inconsistent: Positive results have been reported (1-7), whilst others have shown no associations. Prior to this thesis, no study has assessed the relationship of four dietary patterns to cognition, blood-based and neuroimaging biomarkers of AD in a large highly-characterised ageing cohort. Participants …

Blast-Induced Tinnitus: A Combined Behavioral, Memri, And Electrophysiology Study, Jessica Pengyun Ouyang

Wayne State University Dissertations

ABSTRACT

BLAST-INDUCED TINNITUS: A COMBINED BEHAVIORAL, MEMRE, AND ELECTROPHYSIOLOGY STUDY

by

JESSICA OUYANG

May 2014 Advisor: Drs. Steve Cala & Jinsheng Zhang

Major: Physiology

Degree: Doctor of Philosophy

Tinnitus and hearing loss are the frequent auditory-related co-morbidities of blast trauma. The etiology of blast-induced tinnitus is also muddled by brain mechanisms associated with emotional and cognitive problems such as anxiety, memory loss, and depression. We set out to develop a realistic and ecologically valid model to address changes of cognitive status and psychological state that are associated with blast- induced tinnitus. In this study, 19 adult rats were randomly divided …

Linking Molecular, Electrical And Anatomical Properties Of Human Epileptic Brain, Shruti Bagla

Wayne State University Dissertations

Epilepsy is a common neurological disorder of recurrent unprovoked seizures. It affects almost 1% of the world population. Although there is a wide range of anti-epileptic drugs (AEDs) available, they only treat the seizure symptoms and do not cure the disease itself. The poor role of AEDs can be attributed to the lack of knowledge of exact mechanisms and networks that produce epileptic activities in the neocortex. At present, the best cure for epilepsy is surgical removal of electrically localized epileptic brain tissue. Surgically removed brain tissue presents an excellent opportunity to discover the molecular and cellular basis of human …

The Effects Of Nesting Environment On Neonatal Hypoxic-Ischemic Injury, Laura Grace Rollins

Graduate Masters Theses

Term neonates with hypoxic-ischemic (HI) injury are at risk for devastating neurological sequelae. The objective of this study is to determine if altering the early environment for maternal care-taking impacts the immediate and long-term sequelae of HI offspring. The Rice-Vannucci model was used to induce HI in postnatal day (PND) 7 Long-Evans pups. Litters were assigned to a closed nest (CN) or normal standard housing (SH) condition. Neurobehavioral development, cognitive ability, and stress response were assessed to establish any benefits of the CN condition. Finally, postmortem brain tissue was analyzed for morphometric markers of injury.

Transient And Selective Suppression Of Neural Activity With Infrared Light, Michael W. Jenkins, Hui Lu, Jeffrey M. Mcmanus, Hillel J. Chiel

Faculty Scholarship

Analysis and control of neural circuitry requires the ability to selectively activate or inhibit neurons. Previous work showed that infrared laser light selectively excited neural activity in endogenous unmyelinated and myelinated axons. However, inhibition of neuronal firing with infrared light was only observed in limited cases, is not well understood and was not precisely controlled. Using an experimentally tractable unmyelinated preparation for detailed investigation and a myelinated preparation for validation, we report that it is possible to selectively and transiently inhibit electrically- initiated axonal activation, as well as to both block or enhance the propagation of action potentials of specific …

Alternations Of Nmda And Gabab Receptor Function In Development: A Potential Animal Model Of Schizophrenia, Monica Bolton

UNLV Theses, Dissertations, Professional Papers, and Capstones

Schizophrenia is a debilitating mental disorder that affects up to 3% of the world population. The behavioral symptoms are categorized into positive and negative symptoms, which appear during late adolescence/early adulthood. Unfortunately, the underlying cellular and molecular mechanisms of the disease are poorly understood. Several hypotheses exist to explain mechanisms contributing to these behavioral alterations. One model proposes that a reduced function of the NMDA glutamate receptor on specific GABAergic interneurons may be responsible for deficits in schizophrenia. Post-mortem investigations provide evidence of reductions in both glutamate and GABA-related proteins in patients with schizophrenia. Further, GABAergic interneurons that are activated …

Network Dynamics Of Visual Naming, Christopher R. Conner

Dissertations and Theses (Open Access)

Recognition and naming of objects and actions are fundamental components of language. They involve several different systems working in coordination to accomplish a complex behavior. During visual naming, sensory and semantic processing are carried out by dedicated cortical substrates in the temporal and occipital lobes, while response selection and articulatory planning are handled by prefrontal cortex. Despite decades of research using lesion analysis, functional MRI and electro-encephalography, the precise dynamics involved remain unknown due to the inadequate spatio-temporal resolution of these methodologies. Of particular interest is the organization of semantic knowledge and the degree of serial and parallel organization of …

The Effects Of Chronic Calcium Dysregulation On Behavioral And Pathological Features Of Alzheimer's Disease, Jonathan Sabbagh

UNLV Theses, Dissertations, Professional Papers, and Capstones

Alzheimer's disease (AD) is a progressive neurodegenerative disorder whose etiology is unknown. Recent studies have implicated alterations in calcium homeostasis as a pathogenic contributor to AD. Calcium dysregulation has been observed in aged and AD brains, an event which could potentially facilitate the development of multiple pathologies observed in AD. Specifically, disrupting intracellular calcium levels in vitro has been demonstrated to increase amyloid-beta (Aβ) production, tau phosphorylation, and neuronal loss. However, there is a paucity of data on the behavioral and biochemical consequences of chronic in vivo perturbation of calcium homeostasis. In a series of experiments designed to evaluate the …

Roles Of Neuregulin1 In Neuromuscular Junction Development, Jiajing Wang

Wayne State University Dissertations

Neuromuscular junction (NMJ) development is a multistep process mediated by coordinated interactions between nerve terminals, target muscles, and peri-synaptic glial cells, and thus requires reciprocal signals derived from every cell type. Neuregulin1s (NRG1s) are a family of predominantly neuronal growth and differentiation factors that are important for many aspects of nervous system development. In this thesis, both the effects of NRG1 on NMJ development and reciprocal effects of neurotrophic factors on NRG1 expression were studied as a means to define the complex regulatory communication at the NMJ. Using the chicken embryo as a model, methods were developed to study the …

Investigating Therapeutic Options For Lafora Disease Using Structural Biology And Translational Methods, Amanda R. Sherwood

Theses and Dissertations--Molecular and Cellular Biochemistry

Lafora disease (LD) is a rare yet invariably fatal form of epilepsy characterized by progressive degeneration of the central nervous and motor systems and accumulation of insoluble glucans within cells. LD results from mutation of either the phosphatase laforin, an enzyme that dephosphorylates cellular glycogen, or the E3 ubiquitin ligase malin, the binding partner of laforin. Currently, there are no therapeutic options for LD, or reported methods by which the specific activity of glucan phosphatases such as laforin can be easily measured. To facilitate our translational studies, we developed an assay with which the glucan phosphatase activity of laforin as …

Impairment Of Trkb-Psd-95 Signaling In Angelman Syndrome, Cong Cao, Mengia S. Rioult-Pedotti, Paolo Migani, Crystal J. Yu, Rakesh Tiwari, Keykavous Parang, Mark R. Spaller, Dennis J. Goebel, John Marshall

Pharmacy Faculty Articles and Research

Angelman syndrome (AS) is a neurodevelopment disorder characterized by severe cognitive impairment and a high rate of autism. AS is caused by disrupted neuronal expression of the maternally inherited Ube3A ubiquitin protein ligase, required for the proteasomal degradation of proteins implicated in synaptic plasticity, such as the activity-regulated cytoskeletal-associated protein (Arc/Arg3.1). Mice deficient in maternal Ube3A express elevated levels of Arc in response to synaptic activity, which coincides with severely impaired long-term potentiation (LTP) in the hippocampus and deficits in learning behaviors. In this study, we sought to test whether elevated levels of Arc interfere with brain-derived neurotrophic factor (BDNF) …

Aβ Alters The Dna Methylation Status Of Cell-Fate Genes In An Alzheimer’S Disease Model, Gary D. Isaacs, Noor Taher, Courtney Mckenzie, Rebecca Garrett, Matthew Baker, Nena Fox

Faculty Publications and Presentations

Alzheimer’s disease (AD) is characterized by neurofibrillary tangles and extracellular amyloid-β plaques (Aβ). Despite ongoing research, some ambiguity remains surrounding the role of Aβ in the pathogenesis of this neurodegenerative disease. While several studies have focused on the mutations associated with AD, our understanding of the epigenetic contributions to the disease remains less clear. To that end, we determined the changes in DNA methylation in differentiated human neurons with and without Aβ treatment. We isolated the DNA from neurons treated with Aβ or vehicle, and digested the two samples with either a methylation-sensitive (HpaII) or a methylation-insensitive (MspI) restriction endonuclease. …

Studies Of Regulated Exocytosis From Neuroendocrine Cells, Madhurima Das

Wayne State University Theses

In this thesis we study cargo release and fusion pore dilation during calcium triggered exocytosis and the co-localization of calcium sensing proteins essential for exocytosis, in neuroendocrine cells.

Pancreatic beta cells secrete several hormones, the most studied one being insulin. C-peptide is a protein which is co-stored with and secreted from the same vesicles as insulin. It is found in the soluble phase unlike insulin, which is found in the dense core. The pancreatic beta cells also secrete the Chromogranin B (CgB) which is mostly found in the dense cores of secretory vesicles. In chapter 1, we found that CgB, …

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 …

Progress Towards Understanding Of Mechanisms Of Action Of Potent Multifunctional Disease Modifying Therapeutics For Parkinson's Disease & Investigating The Methamphetamine-Induced Striatal Microglia Activation., Mrudang M. Shah

Wayne State University Dissertations

PROGRESS TOWARDS UNDERSTANDING OF MECHANISMS OF ACTION OF POTENT MULTIFUNCTIONAL DISEASE MODIFYING

THERAPEUTICS FOR PARKINSON'S DISEASE.

by

MRUDANG MANOJKUMAR SHAH

December 2013

Advisor: Dr. Aloke Dutta

Major: Pharmaceutical Sciences

Degree: Doctor of Philosophy

Our long term goal is to design and develop potent multifunctional disease modifying therapeutics for Parkinson's disease. The objective of my dissertation was to understand the mechanisms of action of some potent small molecules (synthesized in our lab) as a disease modifying Parkinson's disease therapeutic. The objective was achieved by pursuing the following two specific aims:

1. Investigating anti-oxidant and neuroprotective effects of a lead molecule (D-512) …

Proteolytic Processing Of The Amyloid Precursor Protein During Apoptosis And Cell Cycle: Implications For Alzheimer's Disease, Tina N. Fiorelli

USF Tampa Graduate Theses and Dissertations

Alzheimer's disease is characterized by the presence of amyloid plaques, made up primarily of Aϐ peptides, and neurofibrillary tangles, containing hyperphosphorylated tau. Aϐ is generated by sequential proteolysis of the amyloid precursor protein (APP) by beta and gamma secretases. The leading hypothesis of Alzheimer's disease pathogenesis is the amyloid cascade hypothesis, which suggests that amyloid is central to the disease process. However, tau pathology correlates more closely with cognitive dysfunction and follows a predictable anatomical course through the brain. We hypothesize that if Aϐ is upstream of tau pathology and tau pathology follows this predictable course through the brain, Aϐ …

The Role Of Molecular Chaperones In The Etiology And Treatment Of Psychiatric Diseases In The Elderly, John Clarence O'Leary

USF Tampa Graduate Theses and Dissertations

The elderly are at increased risk for developing psychiatric diseases, which include Alzheimer's disease, depression, anxiety and suicide. The probability of multiple disease comorbidity is also increased in the elderly. At the cellular level, the loss of protein homeostasis is often at the root of disease emergence, and thus the scientific community is searching for ways to help maintain this balance. A vast group of proteins that are paramount to balancing and counterbalancing protein levels is the molecular chaperone protein group, which has evolved a tremendous variety of functions in the cell. They aid in protein trafficking, folding, receptor signaling, …

The Inflammatory Response Initiated By The Spleen To Ischemic Stroke, Hilary Seifert

USF Tampa Graduate Theses and Dissertations

The peripheral immune system plays a role in delayed neural injury after stroke. This response originates from the spleen as splenectomy prior to middle cerebral artery occlusion (MCAO) in rats significantly reduces infarct volume in the brain. This research is based on the hypothesis that inhibiting the splenic response will reduce neurodegeneration after stroke. Studies in animals have implicated lymphocytes as the immune cell type that is detrimental following MCAO. Interferon gamma (IFNγ) has been identified as a pro-inflammatory cytokine that is also detrimental following stroke. IFNγ is important because it activates microglia and macrophages in a pro-inflammatory nature that …

Exercise-Induced Neuroprotection In A Hemiparkinsonian 6-Hydroxydopamine Rat Model, Merrill Russen Landers

UNLV Theses, Dissertations, Professional Papers, and Capstones

Outside of finding a cure, one of the preeminent goals of research in Parkinson's disease (PD) is finding a neuroprotective treatment that when applied prior to the onset of the disease will decrease the risk and severity of the subsequent disease. One such treatment that has potential as a neuroprotective agent in PD is exercise. Several studies have found forced exercise to be protective of Parkinson's disease in adult rodent models; however, few of these studies have used a design wherein voluntary exercise was evaluated. Moreover, no study has used a true neuroprotective design in which exercise was applied prior …

A Pre-Clinical Assessment Of Minocycline For Treatment Of Chronic Neuropathic Pain After Spinal Cord Injury, Alissa R. Poteete

Dissertations and Theses (Open Access)

Patients living with a spinal cord injury (SCI) often develop chronic neuropathic pain (CNP). Unfortunately, the clinically approved, current standard of treatment, gabapentin, only provides temporary pain relief. This treatment can cause numerous adverse side effects that negatively affect the daily lives of SCI patients. There is a great need for alternative, effective treatments for SCI-dependent CNP.

Minocycline, an FDA-approved antibiotic, has been widely prescribed for the treatment of acne for several decades. However, recent studies demonstrate that minocycline has neuroprotective properties in several pre-clinical rodent models of CNS trauma and disease. Pre-clinical studies also show that short-term minocycline treatment …

Cosmetic Neurology: Enhancement Of The Mind And Attention Deficit Hyperactive Disorder Medication Abuse Among College Students, Mary M. Huff

Senior Honors Theses

Cosmetic neurology is becoming increasingly popular, and it is not just sleep deprived, over worked college students who are interested. People are beginning to seek off-label prescriptions for medications that are typically used to treat disorders such as attention deficit hyperactive disorder (ADHD) or narcolepsy, while researchers are trying to create drugs used solely for mind enhancement purposes. Along with these drugs come many legal and ethical quandaries relating to the regulation of current use as well as the what ifs of future possibilities. A survey was conducted among college students regarding the diagnosis of ADHD, the abuse of ADHD …

The Effects Of Oxygen On The Electrophysiology Of Co2/H+-Chemosensitive And -Insensitive Neurons Of The Solitary Complex Of The Rat, Michael Patrick Matott

USF Tampa Graduate Theses and Dissertations

This study tested the hypothesis that decreasing the control O₂ level from 95% to 40% (5% CO₂ + 55% N₂) maintains viability in caudal solitary complex (cSC) neurons in transverse slices (~300-400ꝳ) prepared from neonatal rat (P2-22) maintained at 32-34°C. The underlying rationale is to reduce exposure to redox and nitrosative stimuli generated during several hours of exposure to 95% O₂ that produces a tissue O₂ tension throughout the slice which is in excess of 203 kPa (2.0 atmospheres absolute,ATA) oxygen. Whole cell recordings of cSC neurons maintained in 40% O₂ exhibited spontaneous …

Hiv-1 Tat Triggers Nuclear Localization Of Zo-1 Via Rho Signaling And Camp Response Element-Binding Protein Activation, Yu Zhong, Bei Zhang, Sung Yong Eum, Michal Toborek

Neurosurgery Faculty Publications

The human immunodeficiency virus (HIV)-specific protein trans-activator of transcription (Tat) can contribute to the dysfunction of brain endothelial cells and HIV trafficking into the brain by disrupting tight junction (TJ) integrity at the blood–brain barrier (BBB) level. Specific TJ proteins, such as zonula occludens (ZO) proteins, localize not only at the cell–cell borders but are also present in the nuclei. The objective of the present study was to evaluate the mechanisms and significance of Tat-induced nuclear localization of ZO-1. Treatment of a brain endothelial cell line (hCMEC/D3 cells) with Tat resulted in a decrease in total levels of ZO-1 but …

Understanding The Gender-Based Mechanism Of Mso In Als Mice: A Metabolic Characterization Of The Sod1-G93a Mouse Model, Monica Ann Bame

Wayne State University Dissertations

Amyotrophic Lateral Sclerosis (ALS) is a devastating neurodegenerative disease characterized by motor neuron death and a corresponding loss of neuromuscular connections resulting in muscle atrophy. Patients become paralyzed shortly after symptom onset and typically die within one to five years of pulmonary complications. ALS is a relatively rare disease, with an overall incidence of approximately 2 in 100,000 people per year and a prevalence of about 5 in 100,000 people. It is typically associated with increasing age and has a slight male prevalence, with a male to female ratio of approximately 3:2. ALS is classified as either familial (the less …

Signals From Intraventricular Depth Electrodes Can Control A Brain-Computer Interface, Jerry J. Shih, Dean J. Krusienski

Electrical & Computer Engineering Faculty Publications

A Brain-Computer Interface (BCI) is a device that enables severely disabled people to communicate and interact with their environments using their brain waves. Most research investigating BCI in humans have used scalp-recorded electroencephalography (EEG). We have recently demonstrated that signals from intracranial electrocorticography (ECoG) and stereotactic depth electrodes (SDE) in the hippocampus can be used to control a BCI P300 Speller paradigm. We report a case in which stereotactic depth electrodes positioned in the ventricle were able to obtain viable signals for a BCI. Our results demonstrate that event-related potentials from intraventricular electrodes can be used to reliably control the …