Nervous System Diseases Commons^™

Neurodevelopmental Vulnerability To Gestational Ozone Exposure, Vishnupriya Alavala, Sarah E. Brent, Christopher G. Canal, Joseph Wang, Russell P. Hunter, Matthew J. Campen, Andrew K. Ottens

Undergraduate Research Posters

Ambient air pollution accounts for about 4.2 million premature deaths annually per the World Health Organization. Ozone (O3) is a highly reactive air pollutant found in smog and is implicated in cellular damage leading to organ dysfunction. Ambient air pollution is associated with neurodevelopmental, behavioral, and cognitive disorders though ozone’s role is unknown. Studies here look at ozone exposure shortly after implantation vs. shortly before term to evaluate differences in neurodevelopmental susceptibility over time.

To inquire on the effects of ozone on the fetal brain, pregnant Sprague-Dawley rats were exposed once to 0.3 ppm of O3 or filtered air (FA) …

Brominated Flame Retardants: A Literature Review Of The Toxicity Mechanisms, Clinical Manifestations, And Current Treatments, Yacobus Christian Prasetyo, Eti Nurwening Sholikhah

Occupational and Environmental Medicine Journal of Indonesia

Brominated flame retardants (BFRs) are organohalogen compounds that can inhibit fire formation and delay its spread in manufacturing materials. BFRs are known to be toxic for the environment and humans. BFRs could persist for years prolonging potential exposure and toxicity to living beings. Indonesia had begun to reduce the use, even though some of toxic BFRs are still illegally circulating. This review aims to describe some aspects of BFRs toxicity including the mechanism, its clinical manifestations, and the current possible treatments. Toxicity after BFRs exposure includes endocrine, neurodevelopmental, and genotoxicity. The toxicity is manifested into some clinical conditions such as …

Selective Gsk3Β Inhibition Mediates An Nrf2-Independent Anti-Inflammatory Microglial Response, Mohamed H. Yousef

Theses and Dissertations

Glycogen Synthase Kinase 3 (GSK3) is associated with the proinflammatory phenotype of microglia and has been shown to act in concert with Nuclear factor kappa B (NF-κB). . GSK3 is also a suppressor of Nuclear factor erythroid 2-related factor 2 (Nrf2), the principal regulator of redox homeostasis. Agreeing with the oxidative paradigm of aging, Nrf2 is often deregulated in parainflammatory and neurodegenerative diseases. In this study, we aimed to explore a multimodal disease-modifying utility of GSK3 inhibition, beyond neuronal proteopathologies, Furthermore, we aimed to underscore the difference in therapeutic value between the two GSK3 paralogs by isoform-selective chemical inhibition.

The …

Psychedelics Can Save: The Scientific And Social Case For Rescheduling Psychedelic Compounds, Galen M. Fader

Chancellor’s Honors Program Projects

No abstract provided.

Open Neuroscience Initiative, Austin Lim

College of Science and Health Full Text Publications

The Open Neuroscience Initiative is a free-to-use textbook

This project began as a means to overcoming the financial burden that face undergraduate neuroscience students when buying textbooks. By compiling and writing a completely free-to-access textbook that covers the foundations of a typical college introduction to neuroscience course, students would have one less obstacle to overcome in their educational career, allowing them to focus their valuable time and attention on learning rather than finances. To make this project a reality, I began with a humble tweet in May 2019 that managed to gain a tiny bit of traction among the neuroscience …

Novel Mechanistic Insights Towards The Repositioning Of Alogliptin In Parkinson's Disease, Eman Ramadan, Marwa M. Safar

Pharmacy

Parkinson's disease (PD) is a progressive neurodegenerative disease that impairs people's lives tremendously. The development of innovative treatment modalities for PD is a significant unmet medical need. The critical function of glucagon-like peptide-1 (GLP-1) in neurodegenerative diseases has raised impetus in investigating the repositioning of a dipeptidyl peptidase IV inhibitor, alogliptin (ALO), as an effective treatment for PD. As a result, the focus of this research was to assess the effect of ALO in a rat rotenone (ROT) model of PD. For 21 days, ROT (1.5 mg/kg) was delivered subcutaneously every other day. ALO (30 mg/kg/day), delivered by gavage for …

Investigating Cannabinoid Type-1 Receptor (Cb1r) Positive Allosteric Modulators (Pams) In Mouse Models Of Overt Cannabimimetic Activity, Subjective Drug Effects, And Neuropathic Pain, Jayden Elmer

Theses and Dissertations

Chronic pain affects between 20 and 30 percent of the adult population in western countries and represents a wide array of specific etiologies (Berge, 2011). Neuropathic pain secondary to traumatic nerve injury, chemotherapeutic toxicity, or diseases (e.g., diabetes mellitus) is often refractory to conventional analgesics, with patients receiving less than 50% pain relief compared to placebo (Finnerup et al. 2010). The endocannabinoid system has shown potential as a therapeutic target for neuropathic pain wherein CB1 agonism via administration of exogenous agonists or pharmacological blockade of endocannabinoid catabolic enzymes exhibits efficacy in reversing allodynia in the chronic constriction injury (CCI) model …

Levels Of Parp1-Immunoreactivity In The Human Brain In Major Depressive Disorder, Aamir Shaikh

Undergraduate Honors Theses

MDD is a severe and debilitating disorder that is associated with a growing global economic burden due to reduced workplace productivity along with increased healthcare resource utilization. Furthermore, depression markedly enhances the risk for suicide, mortality that is especially worrisome given that 30% of depressed individuals have an inadequate response to current antidepressants. This inadequacy of antidepressants necessitates the discovery of a better understanding of the pathobiology of MDD. Most current antidepressants work through monoamine neurotransmitters, and their relative efficacy in depression led to the now dated monoamine-deficiency hypothesis. The limited usefulness of antidepressants has led to a reinvigorated search …

Antidepressants Versus Music Therapy: Which Treatment Is Better For Treating Depression In Parkinson's Disease?, Emaan Dawood

Virginias Collegiate Honors Council Conference

Music and medicine are merging to treat depression in Parkinson’s disease (PD). Antidepressants, the current standard, demonstrate mixed effects in clinical trials, warranting other treatment options. Here, I compare music therapy to antidepressants in the treatment of depression in PD via literature review. Studies of depressed PD patients undergoing music therapy and/or antidepressants were reviewed with attention to variables including depression (on a patient-reported outcome) that were measured pre- and post- therapy. In the music studies, improvements were seen in depression. Methodological inconsistencies across these studies, a paucity of studies, and small sample sizes, however, necessitate more research to reach …

Combination Of Investigational Cell-Based Therapy And Deep Brain Stimulation To Alter The Progression Of Parkinson’S Disease, Nader El Seblani

Theses and Dissertations--Pharmacy

Parkinson’s disease (PD) is the second most common neurodegenerative disorder and the motor symptoms are caused by progressive loss of midbrain dopamine neurons. There is no current treatment that can slow or reverse PD. Our current “DBS-Plus” clinical trial (NCT02369003) features the implantation in vivo of autologous Schwann cells (SCs) derived from a patient’s sural nerve into the substantia nigra pars compacta (SNpc) in combination with Deep Brain Stimulation (DBS) therapy for treating patients with advanced PD.

The central hypothesis of our research is that transdifferentiated SCs within conditioned nerve tissue will deliver pro-regenerative factors to enhance the survival of …

The Use Of Current Steering During Subthalamic Deep Brain Stimulation To Alleviate Upper Limb Symptoms Of Parkinson's Disease, Shabna Iftikar Mohideen

Electronic Thesis and Dissertation Repository

Subthalamic (STN) deep brain stimulation (DBS) is an established treatment to alleviate the appendicular motor symptoms of Parkinson's Disease (PD). Current steering during DBS allows the unequal fractionation of current between two electrodes on the lead, resulting in a non-spherical electrical field. It is hypothesized that the way the electrical field is shaped will affect a patient’s upper limb symptom alleviation. Seven PD patients who underwent bilateral STN-DBS were tested over four weeks post-operation. 16 current fractionation settings were tested each week at an amplitude that increased weekly. Optimal setting was defined as the setting that provided the best …

Intranasal Oxytocin Enhances Connectivity In The Neural Circuitry Supporting Social Motivation And Social Perception In Children With Autism., Ilanit Gordon, Allison Jack, Charlotte M Pretzsch, Brent Vander Wyk, James F Leckman, Ruth Feldman, Kevin A. Pelphrey

Pharmacology and Physiology Faculty Publications

Oxytocin (OT) has become a focus in investigations of autism spectrum disorder (ASD). The social deficits that characterize ASD may relate to reduced connectivity between brain sites on the mesolimbic reward pathway (nucleus accumbens; amygdala) that receive OT projections and contribute to social motivation, and cortical sites involved in social perception. Using functional magnetic resonance imaging and a randomized, double blind, placebo-controlled crossover design, we show that OT administration in ASD increases activity in brain regions important for perceiving social-emotional information. Further, OT enhances connectivity between nodes of the brain's reward and socioemotional processing systems, and does so preferentially for …

Exploring The Effect Of Novel Small Molecules On Oligodendrocyte Precursor Proliferation, Sagune Sakya

University Scholar Projects

Gliomas, a type of brain tumor, can be difficult to treat and have a poor survival rate. One pathway that leads to glioma formation is excessive signaling by platelet derived growth factors (PDGF) through PDGF receptor α (PDGFRα). Through this research, I found that novel compounds that downregulate PDGFRα decrease proliferation of Oli-neu cells, an oligodendrocyte precursor cell model, and identified signaling pathways through which these compounds may exert their effect. Further investigation may identify targets for development of glioma treatments.

Structural Basis For Mutation-Induced Destabilization Of Profilin 1 In Als, Sivakumar Boopathy, Tania Silvas, Maeve Tischbein, Silvia Jansen, Shivender Shandilya, Jill Zitzewitz, John Landers, Bruce Goode, Celia Schiffer, Daryl Bosco

Celia A. Schiffer

Mutations in profilin 1 (PFN1) are associated with amyotrophic lateral sclerosis (ALS); however, the pathological mechanism of PFN1 in this fatal disease is unknown. We demonstrate that ALS-linked mutations severely destabilize the native conformation of PFN1 in vitro and cause accelerated turnover of the PFN1 protein in cells. This mutation-induced destabilization can account for the high propensity of ALS-linked variants to aggregate and also provides rationale for their reported loss-of-function phenotypes in cell-based assays. The source of this destabilization is illuminated by the X-ray crystal structures of several PFN1 proteins, revealing an expanded cavity near the protein core of the …

The Role Of Oxidative Stress In The Mechanisms Of Ammonia-Induced Brain Swelling And Tolerance In The Goldfish (Carassius Auratus), David F. Jones Lisser Mr.

Theses and Dissertations (Comprehensive)

Toxic build-ups of ammonia can cause potentially fatal brain swelling in mammals, but such swelling is reversible in the anoxia- and ammonia-tolerant goldfish (Carassius auratus). The mechanisms of ammonia-induced brain swelling and tolerance remain elusive, but several studies have suggested a role for reactive oxygen species (ROS), which may damage proteins and lipids in the plasma membrane of astrocytes in the brain. As a result, osmotic gradients across cell membranes may be altered leading to water uptake by astrocytes and swelling. While a role for ROS has been proposed in mammals, no studies have addressed this question in …

Role Of Gluk1 Kainate Receptors In Seizures, Epileptic Discharges, And Epileptogenesis, Brita Fritsch, Janine Reis, Maciej Gasior, Rafal M. Kaminski, Michael A. Rogawski

Michael A. Rogawski

Kainate receptors containing the GluK1 subunit have an impact on excitatory and inhibitory neurotransmission in brain regions, such as the amygdala and hippocampus, which are relevant to seizures and epilepsy. Here we used 2-amino-3-(3-hydroxy-5-tert-butylisoxazol-4-yl) propanoic acid (ATPA), a potent and selective agonist of kainate receptors that include the GluK1 subunit, in conjunction with mice deficient in GluK1 and GluK2 kainate receptor subunits to assess the role of GluK1 kainate receptors in provoking seizures and in kindling epileptogenesis. We found that systemic ATPA, acting specifically via GluK1 kainate receptors, causes locomotor arrest and forelimb extension (a unique behavioral characteristic of GluK1 …

Role Of Gluk1 Kainate Receptors In Seizures, Epileptic Discharges, And Epileptogenesis, Brita Fritsch, Janine Reis, Maciej Gasior, Rafal M. Kaminski, Michael A. Rogawski

Michael A. Rogawski

Kainate receptors containing the GluK1 subunit have an impact on excitatory and inhibitory neurotransmission in brain regions, such as the amygdala and hippocampus, which are relevant to seizures and epilepsy. Here we used 2-amino-3-(3-hydroxy-5-tert-butylisoxazol-4-yl) propanoic acid (ATPA), a potent and selective agonist of kainate receptors that include the GluK1 subunit, in conjunction with mice deficient in GluK1 and GluK2 kainate receptor subunits to assess the role of GluK1 kainate receptors in provoking seizures and in kindling epileptogenesis. We found that systemic ATPA, acting specifically via GluK1 kainate receptors, causes locomotor arrest and forelimb extension (a unique behavioral characteristic of GluK1 …

Exploring The Role Of The Solvent In The Denaturation Of A Protein: A Molecular Dynamics Study Of The Dna Binding Domain Of The 434 Repressor, Celia Schiffer, Volker Dötsch, Kurt Wuthrich, Wilfred Van Gunsteren

Celia A. Schiffer

Molecular dynamics simulations of the DNA binding domain of 434 repressor are presented which aim at unraveling the role of solvent in protein denaturation. Four altered solvent models, each mimicking various possible aspects of the addition of a denaturant to the aqueous solvent, were used in the simulations to analyze their effects on the stability of the protein. The solvent was altered by selectively changing the Coulombic interaction between water and protein atoms and between different water molecules. The use of a modified solvent model has the advantage of mimicking the presence of denaturant without having denaturant molecules present in …