Neurosciences Commons^™

Cellular Responses And Tissue Depots For Nanoformulated Antiretroviral Therapy., Andrea L. Martinez-Skinner, Mariluz Araínga, Pavan Puligujja, Diana L. Palandri, Hannah M. Baldridge, Benson J. Edagwa, Joellyn Mcmillan, R. Lee Mosley, Howard Gendelman

Journal Articles: Pharmacology & Experimental Neuroscience

Long-acting nanoformulated antiretroviral therapy (nanoART) induces a range of innate immune migratory, phagocytic and secretory cell functions that perpetuate drug depots. While recycling endosomes serve as the macrophage subcellular depots, little is known of the dynamics of nanoART-cell interactions. To this end, we assessed temporal leukocyte responses, drug uptake and distribution following both intraperitoneal and intramuscular injection of nanoformulated atazanavir (nanoATV). Local inflammatory responses heralded drug distribution to peritoneal cell populations, regional lymph nodes, spleen and liver. This proceeded for three days in male Balb/c mice. NanoATV-induced changes in myeloid populations were assessed by fluorescence-activated cell sorting (FACS) with CD45, …

Cellular Responses And Tissue Depots For Nanoformulated Antiretroviral Therapy., Andrea L. Martinez-Skinner, Mariluz Araínga, Pavan Puligujja, Diana L. Palandri, Hannah M. Baldridge, Benson J. Edagwa, Joellyn Mcmillan, R. Lee Mosley, Howard Gendelman

Journal Articles: Pharmacology & Experimental Neuroscience

Long-acting nanoformulated antiretroviral therapy (nanoART) induces a range of innate immune migratory, phagocytic and secretory cell functions that perpetuate drug depots. While recycling endosomes serve as the macrophage subcellular depots, little is known of the dynamics of nanoART-cell interactions. To this end, we assessed temporal leukocyte responses, drug uptake and distribution following both intraperitoneal and intramuscular injection of nanoformulated atazanavir (nanoATV). Local inflammatory responses heralded drug distribution to peritoneal cell populations, regional lymph nodes, spleen and liver. This proceeded for three days in male Balb/c mice. NanoATV-induced changes in myeloid populations were assessed by fluorescence-activated cell sorting (FACS) with CD45, …

What Does Recent Neuroscience Tell Us About Criminal Responsibility?, Uri Maoz, Gideon Yaffe

Psychology Faculty Articles and Research

A defendant is criminally responsible for his action only if he is shown to have engaged in a guilty act—actus reus (eg for larceny, voluntarily taking someone else’s property without permission)—while possessing a guilty mind—mens rea (eg knowing that he had taken someone else’s property without permission, intending not to return it)—and lacking affirmative defenses (eg the insanity defense or self-defense). We therefore first review neuroscientific studies that bear on the nature of voluntary action, and so could, potentially, tell us something of importance about the actus reus of crimes.Then we look at studies of intention, perception of …

How The Manipulation Of The Ras Homolog Enriched In Striatum Alters The Behavioral And Molecular Progression Of Huntington’S Disease, Franklin A. Lee

University of New Orleans Theses and Dissertations

Huntington’s disease is an incurable, progressive neurological disorder characterized by loss of motor control, psychiatric dysfunction, and eventual dystonia leading to death. Despite the fact that this disorder is caused by a mutation in one single gene, there is no cure. The mutant Huntingtin (mHtt) protein is expressed ubiquitously throughout the brain but frank cell death is limited to the striatum. Recent work has suggested that Rhes, Ras homolog enriched in striatum, which is selectively expressed in the striatum, may play a role in Huntington’s disease neuropathology. In vitro studies have shown Rhes to be an E3 ligase for the …

The Feedforward And Feedback Controls On Gait In Adults With Diabetes, Chun-Kai Huang

Theses & Dissertations

There are nearly 26 million people with diabetes mellitus (DM) in the US, and half of chronic DMs develop somatosensory deficits due to diabetic polyneuropathy or diabetic peripheral neuropathy (DPN). The absence or impaired somatosensory feedback (e.g. touch sensation or joint proprioception) resulted from the damage of large nerve fiber, and motor deficits such as attenuated muscle strength and abnormal plantar pressure of lower extremity have been identified in DPN, and these sensorimotor impairments lead to an increased number of falls. To reduce the risk of falling, a well-coordinated and adapted limb movement driven by the feedforward (anticipatory) and feedback …

Selective Vip Receptor Agonists Facilitate Immune Transformation For Dopaminergic Neuroprotection In Mptp-Intoxicated Mice., Katherine E. Olson, Lisa M. Kosloski-Bilek, Kristi M. Anderson, Breha J. Diggs, Barbara E. Clark, John M. Gledhill, Scott J. Shandler, R. Lee Mosley, Howard Gendelman

Journal Articles: Pharmacology & Experimental Neuroscience

UNLABELLED: Vasoactive intestinal peptide (VIP) mediates a broad range of biological responses by activating two related receptors, VIP receptor 1 and 2 (VIPR1 and VIPR2). Although the use of native VIP facilitates neuroprotection, clinical application of the hormone is limited due to VIP's rapid metabolism and inability to distinguish between VIPR1 and VIPR2 receptors. In addition, activation of both receptors by therapeutics may increase adverse secondary toxicities. Therefore, we developed metabolically stable and receptor-selective agonists for VIPR1 and VIPR2 to improve pharmacokinetic and pharmacodynamic therapeutic end points. Selective agonists were investigated for their abilities to protect mice against MPTP-induced neurodegeneration …

Serotonergic System And Gait: Dorsal Raphe Nucleus As A Control System For Gait, Nahal Farhani

Electronic Thesis and Dissertation Repository

In advanced stages of Parkinson Disease (PD), gait and postural abnormalities emerge. These symptoms are not prominent at early stages of PD despite significant dopaminergic neuronal loss. Gait abnormalities are largely not responsive to levodopa. Therefore, other types of neurons might be responsible for gait abnormalities of the PD.

Since the reticulospinal tract (RET) is mainly implicated in the control of axial muscles, the degeneration of this pathway or populations of neurons controlling this pathway might be responsible for axial symptoms. However, there is limited data about the neurons controlling the RET. Our aim in this study is to delineate …

Criminal Law And Common Sense: An Essay On The Perils And Promise Of Neuroscience, Stephen J. Morse

All Faculty Scholarship

This article is based on the author’s Barrock Lecture in Criminal Law presented at the Marquette University Law School. The central thesis is that the folk psychology that underpins criminal responsibility is correct and that our commonsense understanding of agency and responsibility and the legitimacy of criminal justice generally are not imperiled by contemporary discoveries in the various sciences, including neuroscience and genetics. These sciences will not revolutionize criminal law, at least not anytime soon, and at most they may make modest contributions to legal doctrine, practice, and policy. Until there are conceptual or scientific breakthroughs, this is my story …

Greater Magnocellular Saccadic Suppression In High Versus Low Autistic Tendency Suggests A Causal Path To Local Perceptual Style., David P Crewther, Daniel Crewther, Stephanie Bevan, Melvyn A Goodale, Sheila G Crewther

Brain and Mind Institute Researchers' Publications

Saccadic suppression-the reduction of visual sensitivity during rapid eye movements-has previously been proposed to reflect a specific suppression of the magnocellular visual system, with the initial neural site of that suppression at or prior to afferent visual information reaching striate cortex. Dysfunction in the magnocellular visual pathway has also been associated with perceptual and physiological anomalies in individuals with autism spectrum disorder or high autistic tendency, leading us to question whether saccadic suppression is altered in the broader autism phenotype. Here we show that individuals with high autistic tendency show greater saccadic suppression of low versus high spatial frequency gratings …

Cardiovascular Regulation And Effects Of Respiratory Motor Training In Patients With Chronic Spinal Cord Injury., Bonnie Legg Ditterline

Electronic Theses and Dissertations

This dissertation attempts to discover the mechanisms between cardiovascular and respiratory motor control post spinal cord injury (SCI): in normal, non-injured (NI) persons, cardiovascular regulation is dependent upon respiration, but there is nothing that suggests the mechanism for this relationship post-SCI. Thus we hoped to evaluate various aspects of cardiovascular regulation to further illustrate how this relationship is changed or unchanged by SCI. Chapter I describes the anatomy and physiology of the spine, respiratory system, and cardiovascular system in a NI person, and then describes how the function of these systems is changed by SCI. In addition, we describe therapies …

Theory Of Mind Indexes The Broader Autism Phenotype In Siblings Of Children With Autism At School Age, Tawny Tsang, Kristen Gillepsie-Lynch, Ted Huntman

Publications and Research

Subclinical variants of the social-communicative challenges and rigidity that define autism spectrum disorder (ASD) are known as the broader autism phenotype (BAP). The BAP has been conceptualized categorically (as specific to a subset of relatives of individuals with ASD) and dimensionally (as continuously distributed within the general population). The current study examined the compatibility of these two approaches by assessing associations among autism symptoms and social-communicative skills in young school-age children with ASD, children who have a sibling with ASD, and children without a sibling with ASD. Autism symptomswere associated with reducedTheory ofMind (ToM), adaptive skills, cognitive empathy, and language …

Current Understanding Of The Mechanism Of Action Of The Antiepileptic Drug Lacosamide, Michael A. Rogawski, Azita Tofighy, H Steve White, Alain Matagne, Christian Wolff

Michael A. Rogawski

The antiepileptic drug lacosamide [(R)-2-acetamido-N-benzyl-3-methoxypropanamide], a chiral functionalized amino acid, was originally identified by virtue of activity in the mouse and rat maximal electroshock (MES) test. Attention was drawn to lacosamide because of its high oral potency and stereoselectivity. Lacosamide is also active in the 6 Hz seizure model but inactive against clonic seizures in rodents induced by subcutaneous pentylenetetrazol, bicuculline and picrotoxin. It is also ineffective in genetic models of absence epilepsy. At doses greater than those required to confer protection in the MES test, lacosamide inhibits behavioral and electrographic seizures in hippocampal kindled rats. It also effectively terminates …

Neurophysiological Activity Related To Speech Production: An Erp Investigation, Adithya Chandregowda

USF Tampa Graduate Theses and Dissertations

The event related potential (ERP) technique is enjoying widespread application in neurophysiological research due to its fine temporal resolution. Of relevance to this study are ERPs related to voluntary movements. The precision with which movement related processes could be recorded using the ERP technique was demonstrated by Gilden, Vaughan and Costa (1966) and Kutas and Donchin (1974, 1977, and 1980) who found that the readiness potential (RP) immediately preceding hand movement was larger over the hemisphere contralateral to the responding hand. Given that left hemisphere controls right hand movements and vice versa, their findings confirmed that the lateralized readiness potential …

An Animal Model Of Flashbulb Memory: Insights Into The Time-Dependent Mechanisms Of Memory Enhancement, Laura Ashley Bullard

USF Tampa Graduate Theses and Dissertations

The vivid memory of an emotional event, as well as memory for incidental details associated with the arousing event, has been referred to collectively as a “flashbulb memory”. An important aspect of flashbulb memory in people is that an emotional event enhances memory of contextual details, such as the weather, or clothes one was wearing at the time of the event. Therefore, an emotional event not only produces a detailed memory of the event, itself, but also enhances memory for contextual details that would otherwise not be remembered. The first goal of this work is to describe the development of …

Loss Of Vglut3 Produces Circadian-Dependent Hyperdopaminergia And Ameliorates Motor Dysfunction And L-Dopa-Mediated Dyskinesias In A Model Of Parkinson's Disease., Christopher B. Divito, Kathy Steece-Collier, Daniel T. Case, Sean-Paul G. Williams, Jennifer A. Stancati, Lianteng Zhi, Maria E. Rubio, Caryl E. Sortwell, Timothy J. Collier, David Sulzer, Robert H. Edwards, Hui Zhang, Rebecca P. Seal

Department of Neuroscience Faculty Papers

UNLABELLED: The striatum is essential for many aspects of mammalian behavior, including motivation and movement, and is dysfunctional in motor disorders such as Parkinson's disease. The vesicular glutamate transporter 3 (VGLUT3) is expressed by striatal cholinergic interneurons (CINs) and is thus well positioned to regulate dopamine (DA) signaling and locomotor activity, a canonical measure of basal ganglia output. We now report that VGLUT3 knock-out (KO) mice show circadian-dependent hyperlocomotor activity that is restricted to the waking cycle and is due to an increase in striatal DA synthesis, packaging, and release. Using a conditional VGLUT3 KO mouse, we show that deletion …

Adolescent Intermittent Alcohol Exposure: Deficits In Object Recognition Memory And Forebrain Cholinergic Markers, H. Scott Swartzwelder, Shawn K. Acheson, Kelsey M. Miller, Hannah G. Sexton, Wen Liu, Fulton T. Crews, Mary-Louise Risher

Biomedical Sciences

The long-term effects of intermittent ethanol exposure during adolescence (AIE) are of intensive interest and investigation. The effects of AIE on learning and memory and the neural functions that drive them are of particular interest as clinical findings suggest enduring deficits in those cognitive domains in humans after ethanol abuse during adolescence. Although studies of such deficits after AIE hold much promise for identifying mechanisms and therapeutic interventions, the findings are sparse and inconclusive. The present results identify a specific deficit in memory function after AIE and establish a possible neural mechanism of that deficit that may be of translational …

Hiv-1-Tat Protein Inhibits Sc35-Mediated Tau Exon 10 Inclusion Through Up-Regulation Of Dyrk1a Kinase, Ferdous Kadri, Marco Pacifici, Anna Wilk, Amanda Parker-Struckhoff, Luis Del Valle, Kurt F. Hauser, Pamela E. Knapp, Christopher Parsons, Duane Jeansonne, Adam Lassak, Francesca Peruzzi

School of Medicine Faculty Publications

The HIV-1 transactivator protein Tat is implicated in the neuronal damage that contributes to neurocognitive impairment affecting people living with HIV/AIDS. Aberrant splicing of TAU exon 10 results in tauopathies characterized by alterations in the proportion of TAU isoforms containing three (3R) or four (4R) microtubule-binding repeats. The splicing factor SC35/SRSF2 binds to nuclear RNA and facilitates the incorporation of exon 10 in the TAU molecule. Here, we utilized clinical samples, an animal model, and neuronal cell cultures and found that Tat promotes TAU 3R up-regulation through increased levels of phosphorylated SC35, which is retained in nuclear speckles. This mechanism …

Abcc9/Sur2 In The Brain: Implications For Hippocampal Sclerosis Of Aging And A Potential Therapeutic Target, Peter T. Nelson, Gregory A. Jicha, Wang-Xia Wang, Eseosa T. Ighodaro, Sergey C. Artiushin, Colin G. Nichols, David W. Fardo

Sanders-Brown Center on Aging Faculty Publications

The ABCC9 gene and its polypeptide product, SUR2, are increasingly implicated in human neurologic disease, including prevalent diseases of the aged brain. SUR2 proteins are a component of the ATP-sensitive potassium (“K _ATP ”) channel, a metabolic sensor for stress and/or hypoxia that has been shown to change in aging. The K _ATP channel also helps regulate the neurovascular unit. Most brain cell types express SUR2, including neurons, astrocytes, oligodendrocytes, microglia, vascular smooth muscle, pericytes, and endothelial cells. Thus it is not surprising that ABCC9 gene variants are associated with risk for human brain diseases. For example, Cantu syndrome is …

Functional Differences Between Statistical Learning With And Without Explicit Training., Laura J Batterink, Paul J Reber, Ken A Paller

Brain and Mind Institute Researchers' Publications

Humans are capable of rapidly extracting regularities from environmental input, a process known as statistical learning. This type of learning typically occurs automatically, through passive exposure to environmental input. The presumed function of statistical learning is to optimize processing, allowing the brain to more accurately predict and prepare for incoming input. In this study, we ask whether the function of statistical learning may be enhanced through supplementary explicit training, in which underlying regularities are explicitly taught rather than simply abstracted through exposure. Learners were randomly assigned either to an explicit group or an implicit group. All learners were exposed to …

Dual Optimization Method Of Radiofrequency And Quasistatic Field Simulations For Reduction Of Eddy Currents Generated On 7t Radiofrequency Coil Shielding., Yujuan Zhao, Tiejun Zhao, Shailesh B Raval, Narayanan Krishnamurthy, Hai Zheng, Chad T Harris, William B Handler, Blaine A Chronik, Tamer S Ibrahim

Brain and Mind Institute Researchers' Publications

PURPOSE: To optimize the design of radiofrequency (RF) shielding of transmit coils at 7T and reduce eddy currents generated on the RF shielding when imaging with rapid gradient waveforms.

METHODS: One set of a four-element, 2 × 2 Tic-Tac-Toe head coil structure was selected and constructed to study eddy currents on the RF coil shielding. The generated eddy currents were quantitatively studied in the time and frequency domains. The RF characteristics were studied using the finite difference time domain method. Five different kinds of RF shielding were tested on a 7T MRI scanner with phantoms and in vivo human subjects. …

Behavioral, Perceptual, And Neural Alterations In Sensory And Multisensory Function In Autism Spectrum Disorder., Sarah H Baum, Ryan A Stevenson, Mark T Wallace

Brain and Mind Institute Researchers' Publications

Although sensory processing challenges have been noted since the first clinical descriptions of autism, it has taken until the release of the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) in 2013 for sensory problems to be included as part of the core symptoms of autism spectrum disorder (ASD) in the diagnostic profile. Because sensory information forms the building blocks for higher-order social and cognitive functions, we argue that sensory processing is not only an additional piece of the puzzle, but rather a critical cornerstone for characterizing and understanding ASD. In this review we discuss what …

Steroid Receptor Isoform Expression In Drosophila Nociceptor Neurons Is Required For Normal Dendritic Arbor And Sensitivity, Aidan L. Mcparland, Taylor L. Follansbee, Gwendolyn D. Vesenka, Alexandra E. Panaitiu, Geoffrey K. Ganter

Biology Student Publications

Steroid hormones organize many aspects of development, including that of the nervous system. Steroids also play neuromodulatory and other activational roles, including regulation of sensitivity to painful stimuli in mammals. In Drosophila, ecdysteroids are the only steroid hormones, and therefore the fly represents a simplified model system in which to explore mechanisms of steroid neuromodulation of nociception. In this report, we present evidence that ecdysteroids, acting through two isoforms of their nuclear ecdysone receptor (EcR), modulate sensitivity to noxious thermal and mechanical stimuli in the fly larva. We show that EcRA and EcRB1 are expressed by third instar larvae in …

Differential Modification Of Cortical And Thalamic Projections To Cat Primary Auditory Cortex Following Early- And Late-Onset Deafness., Nicole Chabot, Blake E Butler, Stephen G Lomber

Brain and Mind Institute Researchers' Publications

Following sensory deprivation, primary somatosensory and visual cortices undergo crossmodal plasticity, which subserves the remaining modalities. However, controversy remains regarding the neuroplastic potential of primary auditory cortex (A1). To examine this, we identified cortical and thalamic projections to A1 in hearing cats and those with early- and late-onset deafness. Following early deafness, inputs from second auditory cortex (A2) are amplified, whereas the number originating in the dorsal zone (DZ) decreases. In addition, inputs from the dorsal medial geniculate nucleus (dMGN) increase, whereas those from the ventral division (vMGN) are reduced. In late-deaf cats, projections from the anterior auditory field (AAF) …

Role Of The Slingshot-Cofilin And Ranbp9 Pathways In Alzheimer's Disease Pathogenesis, Jung A Woo

USF Tampa Graduate Theses and Dissertations

Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by two major pathological hallmarks, amyloid plaques and neurofibrillary tangles. The accumulation of amyloid-β protein (Aβ) is an early event associated with synaptic and mitochondrial damage in AD. Therefore, molecular pathways underlying the neurotoxicity and generation of Aβ represent promising therapeutic targets for AD. Recent studies have shown that actin severing protein, Cofilin plays an important role in synaptic remodeling, mitochondrial dysfunction, and AD pathogenesis. However, whether Cofilin is an essential component of AD pathogenesis and how Aβ induced neurotoxicity impinges its signals to Cofilin are unclear.

In my dissertation studies, we …

Preserved Haptic Shape Processing After Bilateral Loc Lesions., Jacqueline C Snow, Melvyn A Goodale, Jody C Culham

Brain and Mind Institute Researchers' Publications

UNLABELLED: The visual and haptic perceptual systems are understood to share a common neural representation of object shape. A region thought to be critical for recognizing visual and haptic shape information is the lateral occipital complex (LOC). We investigated whether LOC is essential for haptic shape recognition in humans by studying behavioral responses and brain activation for haptically explored objects in a patient (M.C.) with bilateral lesions of the occipitotemporal cortex, including LOC. Despite severe deficits in recognizing objects using vision, M.C. was able to accurately recognize objects via touch. M.C.'s psychophysical response profile to haptically explored shapes was also …

“Principal Component Analysis And The Cumulative Gait Index: Translational Tools To Assess Gait Impairments In Rats With Olivocerebellar Ataxia”, Chase Lambert

USF Tampa Graduate Theses and Dissertations

Numerous studies suggest that modulation of the cholinergic system through the use of nicotinic agonists can improve motor function in humans or animals with motor disorders. Specifically, although there are no approved therapeutics for patients with ataxia, the nicotinic receptor agonist varenicline has demonstrated efficacy to improve coordination and gait in several groups of patients with different subtypes of ataxia. Importantly, the mechanism underlying the varenicline’s mechanism of action to improve motor function remains to be elucidated. Thus, the purpose of these experiments was to first quantify gait impairments in rats with olivocerebellar ataxia utilizing an objective treadmill-based system to …

Maternal Postsecondary Education Associated With Improved Cerebellar Growth After Preterm Birth., Mikaela L Stiver, Daphne Kamino, Ting Guo, Angela Thompson, Emma G Duerden, Margot J Taylor, Emily W Y Tam

Brain and Mind Institute Researchers' Publications

The preterm cerebellum is vulnerable to impaired development impacting long-term outcome. Preterm newborns (<32 >weeks) underwent serial magnetic resonance imaging (MRI) scans. The association between parental education and cerebellar volume at each time point was assessed, adjusting for age at scan. In 26 infants, cerebellar volumes at term (P = .001), but not birth (P = .4), were associated with 2-year volumes. For 1 cm(3) smaller cerebellar volume (4% total volume) at term, the cerebellum was 3.18 cm(3) smaller (3% total volume) by 2 years. Maternal postsecondary education was not associated with cerebellar volume at term (P = .16). Maternal …

The Relationship Of Spasticity And Impairments In Force Regulation And Neuromuscular Fatigue Post Stroke, Reivian Berrios Barillas

Dissertations (1934 -)

Hyperreflexia that causes muscle spasticity may contribute to limitations in force regulation and walking ability post stroke. Additionally, neuromuscular fatigue may reduce force regulation, which is important because fatigue can assist to strengthen muscles that control walking. Hyperreflexia may be caused by cortical disinhibition that allows Ia afferents to amplify excitatory synaptic inputs to motoneuron pools. Cortical disinhibition is presumably caused by stroke-related motor cortex damage. Although, other excitatory synaptic sources to motoneurons contribute to motor control, hyperreflexia may be one contributor that affects stroke survivors. However, hyperreflexia is reported infrequently to effect force regulation post stroke. The goal was …

A Neurobiological Pathway That Mediates Stress-Induced Drug Use, Oliver Vranjkovic

Dissertations (1934 -)

Cocaine addiction represents a tremendous health and financial burden on our society and the high rate of relapse to cocaine use in abstinent addicts represents a major barrier to effective therapy. Thus, understanding the factors that contribute to relapse and the underlying neurobiological processes is important for guiding the development of treatment for addiction. Stressful life events often trigger drug use in recovering addicts. The contribution of stress to drug use is problematic due to the unpredictable and often uncontrollable nature of stress. A growing literature indicates that norepinephrine and corticotropin releasing factor (CRF) in the brain play key roles …

Initial Validation Of A Novel Method Of Presurgical Language Localization Through Functional Connectivity (Fcmri), Stephanie M. Noble, Dustin Scheinost, Susan Y. Bookheimer, Patricia Walshaw, R Todd Constable, Christopher F. Benjamin

Yale Day of Data

OBJECTIVE: Neurosurgery is potentially curative in chronic epilepsy but can only be offered to patients if the surgical risk to language is known. Clinical functional magnetic resonance imaging (fMRI) is an ideal, noninvasive method for localizing language cortex yet remains to be validated for this purpose. We have recently presented a novel method for localizing language cortex. Here we present a preliminary evaluation of this method’s validity. We hypothesized language regions identified using this novel method would demonstrate stronger functional connectivity than randomly generated set of proximal networks. METHOD: fMRI data were collected from sixteen temporal lobe patients …