Neurosciences Commons^™

Selecting Optimal Combinations Of Transcription Factors To Promote Axon Regeneration: Why Mechanisms Matter, Ishwariya Venkatesh, Murray G. Blackmore

Biomedical Sciences Faculty Research and Publications

Recovery from injuries to the central nervous system, including spinal cord injury, is constrained in part by the intrinsically low ability of many CNS neurons to mount an effective regenerative growth response. To improve outcomes, it is essential to understand and ultimately reverse these neuron-intrinsic constraints. Genetic manipulation of key transcription factors (TFs), which act to orchestrate production of multiple regeneration-associated genes, has emerged as a promising strategy. It is likely that no single TF will be sufficient to fully restore neuron-intrinsic growth potential, and that multiple, functionally interacting factors will be needed. An extensive literature, mostly from non-neural cell …

Molecular Mechanism: The Human Dopamine Transporter Histidine 547 Regulates Basal And Hiv-1 Tat Protein-Inhibited Dopamine Transport, Pamela M. Quizon, Wei-Lun Sun, Yaxia Yuan, Narasimha M. Midde, Chang-Guo Zhan, Jun Zhu

Molecular Modeling and Biopharmaceutical Center Faculty Publications

Abnormal dopaminergic transmission has been implicated as a risk determinant of HIV-1-associated neurocognitive disorders. HIV-1 Tat protein increases synaptic dopamine (DA) levels by directly inhibiting DA transporter (DAT) activity, ultimately leading to dopaminergic neuron damage. Through integrated computational modeling prediction and experimental validation, we identified that histidine547 on human DAT (hDAT) is critical for regulation of basal DA uptake and Tat-induced inhibition of DA transport. Compared to wild type hDAT (WT hDAT), mutation of histidine547 (H547A) displayed a 196% increase in DA uptake. Other substitutions of histidine547 showed that DA uptake was not altered in H547R but decreased by 99% …

An Examination Of The Neural Unreliability Thesis Of Autism, John Butler, Sophie Molholm, Gizely Andrade, John J. Foxe

Articles

An emerging neuropathological theory of Autism, referred to here as “the neural unreliability thesis,” proposes greater variability in moment-to-moment cortical representation of environmental events, such that the system shows general instability in its impulse response function. Leading evidence for this thesis derives from functional neuroimaging, a methodology ill-suited for detailed assessment of sensory transmission dynamics occurring at the millisecond scale. Electrophysiological assessments of this thesis, however, are sparse and unconvincing. We conducted detailed examination of visual and somatosensory evoked activity using high-density electrical mapping in individuals with autism (N = 20) and precisely matched neurotypical controls (N = 20), recording …

An Examination Into The Relationship Between Iron Deficiency And Postpartum Depression, Sara A. Burroughs

Senior Honors Theses

Postpartum depression is recognized as the most common complication of childbearing; however, its etiology remains fairly undetermined. Many different influences have been hypothesized as to what may cause postpartum depression, including changes in levels of various hormones (such as estrogen and progesterone), a decrease in serotonin, low levels of vitamin D, social factors, and iron deficiency. The lack of strong evidence for one specific cause makes it fairly clear that there are many factors that play a role in the development of postpartum depression. Iron deficiency is one issue that is thought to contribute to the development of postpartum depression …

Self-Reported Sleep Apnea And Dementia Risk: Findings From The Prevention Of Alzheimer's Disease With Vitamin E And Selenium Trial, Xiuhua Ding, Richard J. Kryscio, Joshua Turner, Gregory A. Jicha, Gregory E. Cooper, Allison M. Caban-Holt, Frederick A. Schmitt, Erin L. Abner

Sanders-Brown Center on Aging Faculty Publications

OBJECTIVES: To investigate the association between baseline sleep apnea and risk of incident dementia in the Prevention of Alzheimer's Disease with Vitamin E and Selenium (PREADViSE) study and to explore whether the association depends on apolipoprotein E (APOE) ɛ4 allele status.

DESIGN: Secondary analysis based on data collected during PREADViSE.

SETTING: Participants were assessed at 128 local clinical study sites during the clinical trial phase and later were followed by telephone from a centralized location.

PARTICIPANTS: Men enrolled in PREADViSE (without dementia or other active neurological conditions that affect cognition such as major psychiatric disorders, including depression; N = …

Post-Concussion Experiences Of Collegiate Student-Athletes, Kaitlin Iris Singer

Doctoral Dissertations

Sports-related concussions are a major public health concern affecting a significant number of collegiate student-athletes. Medical and public health research has addressed every aspect of concussion management processes including concussion education, medical diagnosis, recovery, and returning to sport and classroom. This research has led to several best-practices for concussion management. Since 2010, the NCAA has mandated that its member institutions maintain concussion management policies and procedures. However, the current recommendations, based primarily on medical research, have been found in quantitative studies of the behaviors and practices of athletic trainers, coaches, and student-athletes to be ineffective. To date, no studies have …

Epigenetic Profiling Reveals A Developmental Decrease In Promoter Accessibility During Cortical Maturation In Vivo, Ishwariya Venkatesh, Matthew T. Simpson, Denise M. Coley, Murray G. Blackmore

Biomedical Sciences Faculty Research and Publications

Axon regeneration in adult central nervous system (CNS) is limited in part by a developmental decline in the ability of injured neurons to re-express needed regeneration associated genes (RAGs). Adult CNS neurons may lack appropriate pro-regenerative transcription factors, or may display chromatin structure that restricts transcriptional access to RAGs. Here we performed epigenetic profiling around the promoter regions of key RAGs, and found progressive restriction across a time course of cortical maturation. These data identify a potential intrinsic constraint to axon growth in adult CNS neurons. Neurite outgrowth from cultured postnatal cortical neurons, however, proved insensitive to treatments that improve …

Genomics And Csf Analyses Implicate Thyroid Hormone In Hippocampal Sclerosis Of Aging, Peter T. Nelson, Yuriko Katsumata, Kwangsik Nho, Sergey C. Artiushin, Gregory A. Jicha, Wang-Xia Wang, Erin L. Abner, Andrew J. Saykin, Walter A. Kukull, Alzheimer’S Disease Neuroimaging Initiative (Adni), David W. Fardo

Sanders-Brown Center on Aging Faculty Publications

We report evidence of a novel pathogenetic mechanism in which thyroid hormone dysregulation contributes to dementia in elderly persons. Two single nucleotide polymorphisms (SNPs) on chromosome 12p12 were the initial foci of our study: rs704180 and rs73069071. These SNPs were identified by separate research groups as risk alleles for non-Alzheimer’s neurodegeneration. We found that the rs73069071 risk genotype was associated with hippocampal sclerosis (HS) pathology among people with the rs704180 risk genotype (National Alzheimer’s Coordinating Center/Alzheimer’s Disease Genetic Consortium data; n = 2113, including 241 autopsy-confirmed HS cases). Furthermore, both rs704180 and rs73069071 risk genotypes were associated with widespread brain …

Evaluating Cardiovascular Dysfunction During Increased Activity And Exercise Rehabilitation Following Incomplete Thoracic Spinal Cord Injury In The Adult Rat., Kathryn A. Harman

Electronic Theses and Dissertations

Spinal cord injury (SCI) results in whole-body dysfunction. While the majority of SCI research is focused on improving locomotor function after injury, cardiovascular (CV) disease continues to be the leading cause of morbidity in the chronic SCI patient population. The combination of injury-induced destruction of autonomic pathways, maladaptive plasticity within lumbosacral circuits, and the progressive decline in physical fitness contribute to the poor CV status of SCI individuals. Currently, there is little emphasis on implementing appropriately-timed acute rehabilitation techniques aimed to curtail maladaptive remodeling and improve CV outcomes. Furthermore, no pre-clinical or clinical studies have investigated the most appropriate time-course …

Dissecting The Physiological Roles Of Ulk1/2 In The Mouse Brain, Bo Wang

Theses and Dissertations (ETD)

Mammalian UNC-51–like kinases 1 and 2 (ULK1 and ULK2), Caenorhabditis elegans UNC-51 and Drosophila melanogaster Atg1 are redundant serine/threonine kinases that regulate flux through the autophagy pathway in response to various types of cellular stress. C. elegans UNC-51 and D. melanogaster Atg1 also promote axonal growth and defasciculation, and disruption of these genes results in defects in axon guidance in invertebrates. Germline Ulk1/2-deficient mice die perinatally. Therefore, we used a conditional-knockout approach to investigate the roles of ULK1/2 in the brain. Mice lacking Ulk1 and Ulk2 in their central nervous systems (CNS) showed defects in axonal pathfinding and defasciculation affecting …

Development, Validation And Application Of A New Fornix Template For Studies Of Aging And Preclinical Alzheimer's Disease, Christopher A. Brown, Nathan F. Johnson, Amelia J. Anderson-Mooney, Gregory A. Jicha, Leslie M. Shaw, John Q. Trojanowski, Linda J. Van Eldik, Frederick A. Schmitt, Charles D. Smith, Brian T. Gold

Physical Therapy Faculty Publications

We developed a merged younger-older adult template of the fornix and demonstrated its utility for studies of aging and preclinical Alzheimer's disease (AD). In Experiment 1, probabilistic tractography was used to reconstruct the fornix in younger and older adults and successful streamlines were then averaged to create a merged template in standard space. The new template includes the majority of the fornix from the hippocampal formation to the subcallosal region and the thalamus/hypothalamus. In Experiment 2, the merged template was validated as an appropriate measure for studies of aging, with comparisons against manual tracing measures indicating identical spatial coverage in …

Proceedings Of The Fourth Annual Deep Brain Stimulation Think Tank: A Review Of Emerging Issues And Technologies, Wissam Deeb, James J. Giordano, Peter J. Rossi, Alon Y. Mogilner, Aysegul Gunduz, Jack W. Judy, Bryan T. Klassen, Christopher R. Butson, Craig Van Horne, Damiaan Deny, Darin D. Dougherty, David Rowell, Greg A. Gerhardt, Gwenn S. Smith, Francisco A. Ponce, Harrison C. Walker, Helen M. Bronte-Stewart, Helen S. Mayberg, Howard J. Chizeck, Jean-Philippe Langevin, Jens Volkmann, Jill L. Ostrem, Jonathan B. Shute, Joohi Jimenez-Shahed, Kelly D. Foote, Aparna Wagle Shukla, Marvin A. Rossi, Michael Oh, Michael Pourfar, Paul B. Rosenberg

Neurosurgery Faculty Publications

This paper provides an overview of current progress in the technological advances and the use of deep brain stimulation (DBS) to treat neurological and neuropsychiatric disorders, as presented by participants of the Fourth Annual DBS Think Tank, which was convened in March 2016 in conjunction with the Center for Movement Disorders and Neurorestoration at the University of Florida, Gainesveille FL, USA. The Think Tank discussions first focused on policy and advocacy in DBS research and clinical practice, formation of registries, and issues involving the use of DBS in the treatment of Tourette Syndrome. Next, advances in the use of neuroimaging …

The Effects Of Synthetic And Dietary Therapeutics On Learning, Memory, Motor Coordination, And Seizure In An Angelman Syndrome Mouse Model, Stephanie Lynn Ciarlone

USF Tampa Graduate Theses and Dissertations

Angelman syndrome (AS) is a rare genetic and neurological disorder presenting with severe developmental delay, ataxia, epilepsy, and lack of speech. AS is associated with a neuron-specific loss of function of the maternal UBE3A allele, a gene encoding an E3 ubiquitin ligase. Currently, no cure exists for this disorder; however, recent research using an AS mouse model suggests that pharmacological intervention is plausible, and can alleviate some of the detrimental phenotypes reported in AS patients.

Although there is no curative treatment for AS, seizure medication and behavioral therapies are most commonly prescribed in order to minimize symptoms. However, these options …

Hypercapnic Hyperoxia Increases Free Radical Production And Cellular Excitability In Rat Caudal Solitary Complex Brain Slice Neurons, Geoffrey Edward Ciarlone

USF Tampa Graduate Theses and Dissertations

The caudal solitary complex (cSC) is a cardiorespiratory integrative center in the dorsal medulla oblongata that plays a vital role in the central CO₂-chemoreceptive network. Neurons in this area respond to hypercapnic acidosis (HA) by a depolarization of the membrane potential and increase in firing rate, however a definitive mechanism for this response remains unknown. Likewise, CO₂-chemoreceptive neurons in the cSC respond to hyperoxia in a similar fashion, but via a free radical mediated mechanism. It remains unknown if the response to increased pO₂ is merely an increase in redox signaling, or if it’s the …

Administration Of Electroconvulsive Therapy For Depression Associated With Deep Brain Stimulation In A Patient With Post-Traumatic Parkinson's Disease: A Case Study, Miles G. Cunningham, Golnaz Yadollahikhales, Gordana Vitaliano, Craig Van Horne

Neurosurgery Faculty Publications

Background: Deep brain stimulation (DBS) has been shown to be effective for parkinsonian symptoms poorly responsive to medications. DBS is typically well-tolerated, as are the maintenance battery changes. Here we describe an adverse event during a battery replacement procedure that caused rapid onset of severe depression.

Case Presentation: The patient is a 58-year-old woman who was in a serious motor vehicle accident and sustained a concussion with loss of consciousness. Within weeks of the accident she began developing parkinsonian symptoms that progressively worsened over the subsequent 10 years. Responding poorly to medications, she received DBS, which controlled her movement symptoms. …

Regulation Of Palmitoylation Enzymes And Substrates By Intrinsically Disordered Regions, Krishna D. Reddy

USF Tampa Graduate Theses and Dissertations

Protein palmitoylation refers to the process of adding a 16-carbon saturated fatty acid to the cysteine of a substrate protein, and this can in turn affect the substrate’s localization, stability, folding, and several other processes. This process is catalyzed by a family of 23 mammalian protein acyltransferases (PATs), a family of transmembrane enzymes that modify an estimated 10% of the proteome. At this point in time, no structure of a protein in this family has been solved, and therefore there is poor understanding about the regulation of the enzymes and their substrates. Most proteins, including palmitoylation enzymes and substrates, have …

Estimating Propensity Parameters Using Google Pagerank And Genetic Algorithms, David Murrugarra, Jacob Miller, Alex N. Mueller

Mathematics Faculty Publications

Stochastic Boolean networks, or more generally, stochastic discrete networks, are an important class of computational models for molecular interaction networks. The stochasticity stems from the updating schedule. Standard updating schedules include the synchronous update, where all the nodes are updated at the same time, and the asynchronous update where a random node is updated at each time step. The former produces a deterministic dynamics while the latter a stochastic dynamics. A more general stochastic setting considers propensity parameters for updating each node. Stochastic Discrete Dynamical Systems (SDDS) are a modeling framework that considers two propensity parameters for updating each node …

A Non-Canonical Role For Choline Acetyltransferase In Chromatin Organization And The Response To Beta-Amyloid, Warren R. Winick-Ng

Electronic Thesis and Dissertation Repository

The three-dimensional structure of chromatin is essential for context-dependent regulation of gene expression in post-mitotic neurons. Chromosomal rearrangements have been observed in the aging brain, and proteins involved in chromatin organization have altered expression and/or localization in Alzheimer’s disease (AD). A human- and primate-specific transcript of choline acetyltransferase produces an 82-kDa protein (82-kDa ChAT) that is localized to the nucleus of cholinergic neurons, but is found in the cytoplasm in individuals with mild cognitive impairment (MCI) and AD. The function of the 82-kDa ChAT protein is unknown, though recent evidence suggests it has a role in gene expression changes in …

Hormone Replacement Therapy (Hrt) Modulates Peripheral And Central Auditory System Processing With Aging, Tanika Williamson

USF Tampa Graduate Theses and Dissertations

After the findings were reported for the Women’s Health Initiative (WHI) study in the past decade, there has been a significant decline in the overall use of hormone replacement therapy (HRT) among women. However, there are still millions of middle-aged, menopausal women in the U.S. who are currently undergoing hormone therapy. Their reasons for continuing treatment include relief of severe menopausal symptoms, aid in the management of osteoporosis and reduction in the risk of colon cancer (Ness et al., 2005). The purpose of the following investigation was to evaluate the impact of HRT on the central and peripheral auditory systems …

Intraocular Pressure Sensing And Control For Glaucoma Research, Simon Antonio Bello

USF Tampa Graduate Theses and Dissertations

Animal models of ocular hypertension are important for glaucoma research but come with experimental costs. Available methods of intraocular pressure (IOP) elevation are not always successful, the amplitude and time course of IOP changes are unpredictable and irreversible, and IOP measurement by tonometry is laborious. This dissertation focuses on the development and implementation of two novel systems for monitoring and controlling IOP without these limitations. The first device consists of a cannula implanted in the anterior chamber of the eye, a pressure sensor that continually measures IOP, and a bidirectional pump driven by control circuitry that can infuse or withdraw …

Brainwave Signatures For Detecting Malingered Neurocognitive Deficit (Mncd), Esias K. Bedingar

Posters-at-the-Capitol

Traumatic brain injury is a major public health concern in the United States, affecting up to 1.7 million people each year. Mild traumatic brain injury (mTBI) accounts for 80% of these cases. Various tests have been created in order to document brain injury and evaluate cognitive functions. However, neuropsychologists report that up to 40% of individuals undergoing evaluations following mTBI may be malingering deficits. This points to a need for innovative and non-invasive approaches to validating mTBI while identifying malingerers.

The aim of this study was to utilize neuroimaging and behavioral approaches to detect MNCD by comparing the reaction times …

The Serotonin Transporter Promoter Polymorphism Moderates The Continuity Of Behavioral Inhibition In Early Childhood., Victoria C Johnson, Katie R Kryski, Haroon I Sheikh, Heather J Smith, Shiva M Singh, Elizabeth P Hayden

Brain and Mind Institute Researchers' Publications

Persistently elevated behavioral inhibition (BI) in children is a marker of vulnerability to psychopathology. However, little research has considered the joint influences of caregiver and child factors that may moderate the continuity of BI in early childhood, particularly genetic variants that may serve as markers of biological plasticity, such as the serotonin transporter linked polymorphic region (5-HTTLPR). We explored this issue in 371 preschoolers and their caregivers, examining whether parent characteristics (i.e., overinvolvement or anxiety disorder) and child 5-HTTLPR influenced the continuity of BI between ages 3 and 5. Measures were observational ratings of child BI, observational and questionnaire measures …

When Empathy Bites Back: Cautionary Tales From Neuroscience For Capital Sentencing, Sheri Lynn Johnson, Amelia Courtney Hritz, Caisa Elizabeth Royer, John H. Blume

Cornell Law Faculty Publications

The neuroscience of empathy provides one more reason to believe that the decision to sentence another human being to death is inevitably an arbitrary one, and one that cannot be divorced from either race or caprice. While we can tinker with aspects of capital trials that exacerbate caprice and discrimination stemming from empathy, we cannot alter basic neural responses to the pain of others and therefore cannot rationalize (in either sense of the word) empathic responses.

Resting-State Network-Specific Breakdown Of Functional Connectivity During Ketamine Alteration Of Consciousness In Volunteers., Vincent Bonhomme, Audrey Vanhaudenhuyse, Athena Demertzi, Marie-Aurélie Bruno, Oceane Jaquet, Mohamed Ali Bahri, Alain Plenevaux, Melanie Boly, Pierre Boveroux, Andrea Soddu, Jean François Brichant, Pierre Maquet, Steven Laureys

Brain and Mind Institute Researchers' Publications

BACKGROUND: Consciousness-altering anesthetic agents disturb connectivity between brain regions composing the resting-state consciousness networks (RSNs). The default mode network (DMn), executive control network, salience network (SALn), auditory network, sensorimotor network (SMn), and visual network sustain mentation. Ketamine modifies consciousness differently from other agents, producing psychedelic dreaming and no apparent interaction with the environment. The authors used functional magnetic resonance imaging to explore ketamine-induced changes in RSNs connectivity.

METHODS: Fourteen healthy volunteers received stepwise intravenous infusions of ketamine up to loss of responsiveness. Because of agitation, data from six subjects were excluded from analysis. RSNs connectivity was compared between absence of …

Metabolic Therapy For Temporal Lobe Epilepsy In A Dish: Investigating Mechanisms Of Ketogenic Diet Using Electrophysiological Recordings In Hippocampal Slices, Masahito Kawamura Jr., David N. Ruskin, Susan A. Masino

Faculty Scholarship

The hippocampus is prone to epileptic seizures and is a key brain region and experimental platform for investigating mechanisms associated with the abnormal neuronal excitability that characterizes a seizure. Accordingly, the hippocampal slice is a common in vitro model to study treatments that may prevent or reduce seizure activity. The ketogenic diet is a metabolic therapy used to treat epilepsy in adults and children for nearly 100 years; it can reduce or eliminate even severe or refractory seizures. New insights into its underlying mechanisms have been revealed by diverse types of electrophysiological recordings in hippocampal slices. Here we review these …

Positive Allosteric Modulator Of Gabab Receptor Alters Behavioral Effects But Not Afterdischarge Progression Induced By Partial Hippocampal Kindling., L Stan Leung, Miao Jin, Liangwei Chu, Jingyi Ma

Physiology and Pharmacology Publications

Hippocampal seizures decreased the function of GABAB receptors, which may further increase seizure susceptibility and contribute to development of schizophrenia-like behaviors. Recent literature indicates that GABAB receptor agonist may normalize schizophrenia-like behaviors and prevent drug-induced behavioral sensitization. We hypothesized that positive modulation of GABAB receptor function during seizure induction will reduce seizure-induced schizophrenia-like behaviors. Using a partial hippocampal kindling model, afterdischarges were induced after injection of saline or dimethyl sulfoxide (vehicle-kindled rats), or a GABAB receptor positive allosteric modulator CGP7930, at 1 mg/kg i.p. (CGP1-kindled) or 5 mg/kg i.p. (CGP5-kindled). The increase in the primary afterdischarge duration during kindling was …

Gradenigo Syndrome: A Rare Complication Of Otitis Media, Paul Brent Ferguson, Md

Paul Ferguson

Gradenigo syndrome is a very rare complication of otitis media that if left unrecognized and subsequently untreated will result in severe neurologic sequelae. Gradenigo Syndrome clinically represented by the triad of otitis media, ipsilateral, abducens nerve palsy and dysasthesia within the V1 and V2 divisions of the trigeminal nerve branches. We describe a 4 year-old patient who presented with headache, facial pain, diplopia and a recent history of upper respiratory tract symptomatology. Examination revealed an abducens palsy with subsequent magnetic resonance imaging demonstrating inflammation in the left petrous apex and along the tracts of the 6th, 7th, and 8th cranial …

Designing The Haptic Interface For Morse Code, Michael Walker

USF Tampa Graduate Theses and Dissertations

Two siblings have a muscular degenerative condition that has rendered them mostly blind, deaf and paraplegic. Currently, the siblings receive communication by close range sign language several feet in front of their vision. Due to the degenerative nature of their condition, it is believed that the siblings will eventually become completely blind and unable to communicate in this fashion. There are no augmented communication devices on the market that allow communication reception for individuals who cannot see, hear or possess hand dexterity (such as braille reading). To help the siblings communicate, the proposed communication device will transmit Morse code information …

Development Of Anatomical And Functional Magnetic Resonance Imaging Measures Of Alzheimer Disease, Samaneh Kazemifar

Electronic Thesis and Dissertation Repository

Alzheimer disease is considered to be a progressive neurodegenerative condition, clinically characterized by cognitive dysfunction and memory impairments. Incorporating imaging biomarkers in the early diagnosis and monitoring of disease progression is increasingly important in the evaluation of novel treatments. The purpose of the work in this thesis was to develop and evaluate novel structural and functional biomarkers of disease to improve Alzheimer disease diagnosis and treatment monitoring. Our overarching hypothesis is that magnetic resonance imaging methods that sensitively measure brain structure and functional impairment have the potential to identify people with Alzheimer’s disease prior to the onset of cognitive decline. …

Spinal Cord Injury And Autonomic Dysreflexia- A Case Report, Apurva Bhatt, Brit Moore, Talal Asif, Kristy E. Steigerwalt, Rebecca R. Pauly

Marshall Journal of Medicine

Autonomic dysreflexia (AD) is a life threatening condition affecting patients with spinal cord lesions T6 level and above. A 51 year old male with a history of paraplegia due to a C6 spinal cord injury (30 years prior) presented with recurrent debilitating episodic diaphoresis, hypertension, low body temperature, and bradycardia. Previous hospitalizations presumed sepsis from UTI to be the etiology, however on further evaluation his symptoms were consistent with undiagnosed AD. This article describes a unique case presentation and reviews AD in depth, including the etiology, pathophysiology and management.