Neuroscience and Neurobiology Commons^™

Tet1-Mediated Dna Hydroxymethylation Regulates Adult Remyelination In Mice, Sarah Moyon, Rebecca Frawley, Damien Marechal, Dennis Huang, Katy L.H. Marshall-Phelps, Linde Kegel, Boguslawa Sadowski, Yong-Hui Jiang, David A. Lyons, Wiebke Möbius, Patrizia Casaccia

Advanced Science Research Center

The mechanisms regulating myelin repair in the adult central nervous system (CNS) are unclear. Here, we identify DNA hydroxymethylation, catalyzed by the Ten-Eleven- Translocation (TET) enzyme TET1, as necessary for myelin repair in young adults and defective in old mice. Constitutive and inducible oligodendrocyte lineage-specific ablation of Tet1 (but not of Tet2), recapitulate this age-related decline in repair of demyelinated lesions. DNA hydroxymethylation and transcriptomic analyses identify TET1-target in adult oligodendrocytes, as genes regulating neuro-glial communication, including the solute carrier (Slc) gene family. Among them, we show that the expression levels of the Na+/K+/Cl− transporter, SLC12A2, are …

The Atr-Chek1 Pathway Inhibits Axon Regeneration In Response To Piezo-Dependent Mechanosensation, Feng Li, Tsz Y. Lo, Leann Miles, Qin Wang, Harun N. Noristani, Dan Li, Jingwen Niu, Shannon Trombley, Jessica I. Goldshteyn, Chuxi Wang, Shuchao Wang, Jingyun Qiu, Katarzyna Pogoda, Kalpana Mandal, Megan Brewster, Panteleimon Rompolas, Ye He, Pau A. Janmey, Gareth M. Thomas, Shuxin Li, Yuanquan Song

Advanced Science Research Center

Atr is a serine/threonine kinase, known to sense single-stranded DNA breaks and activate the DNA damage checkpoint by phosphorylating Chek1, which inhibits Cdc25, causing cell cycle arrest. This pathway has not been implicated in neuroregeneration. We show that in Drosophila sensory neurons removing Atr or Chek1, or overexpressing Cdc25 promotes regeneration, whereas Atr or Chek1 overexpression, or Cdc25 knockdown impedes regeneration. Inhibiting the Atr-associated checkpoint complex in neurons promotes regeneration and improves synapse/behavioral recovery after CNS injury. Independent of DNA damage, Atr responds to the mechanical stimulus elicited during regeneration, via the mechanosensitive ion channel Piezo and its downstream NO …

The Role Of Leadership Communication Patterns On Organizational Effectiveness, Nidal Pascoe

Walden Dissertations and Doctoral Studies

Abstract The communication patterns of leaders in the workplace are vital to ensuring productivity and meeting organizational mission and goals. The quality of workplace communication from the leaders impacts the perceptions of employees about the workplace and their ability to fulfill organizational missions and goals. Communication can be delivered through multiple technological means, in person, and in writing. Message delivery also can convey the tone of the sender. The purpose of this case study was to identify the communication patterns between the executive leaders and six of eight site leaders of a nonprofit counseling center focused on serving children and …

Multimodal Neuroscience Data Modeling And Inference, Sima Azizi

Doctoral Dissertations

“Mathematical models can be combined with deep learning and machine learning methods to provide new insights in neuroscience. The field of neuroscience is characterized by rich datasets that include fluid biomarkers, EEG signals, and advanced neuroimages. Recent advances in natural language processing have led to the opportunity to gain additional insights from rapidly growing text databases as well as electronic health records. In this research, we focus on applying computational intelligence methods to the analysis of three different complex data sources: blood levels of disease biomarkers, EEG signals from schizophrenic patients, and disease phenotypes encoded in electronic health records. First, …

Using Zebrafish To Elucidate The Expression And Gene Regulatory Network Of The Genomic Screen Homeobox Transcription Factors And Bring Innovative Science Learning Experiences To West Virginia, Rebecca Ann Coltogirone

Graduate Theses, Dissertations, and Problem Reports (ETD)

Central nervous system (CNS) development requires a code of regionally expressed transcription factors that impart initial neuronal cell identity, connectivity, and function. The absence of a transcription factor code would eliminate the neurodevelopmental logic producing diverse cell types in the CNS. Furthermore, early disruptions in transcription factor expression can affect later connectivity and function of neuronal circuits mediating sensory processing, defects in which are often observed as comorbid with various neurodevelopmental disorders (NDDs). Characterizing transcription factor expression and function is therefore an essential step in discerning the molecular mechanisms underlying human NDDs. genomic screen homeobox 1 and 2 (gsx1 …

Pharmacokinetics And Reward-Related Behaviors Of Ethanol In Male And Female Japanese Quail (Coturnix Japonica), Shannon Eaton

Theses and Dissertations--Psychology

Ethanol is one of the most widely used and abused drugs. Problem use is associated with many different health problems and the economic burden is in the billions of dollars. Additionally, many people have difficulty controlling their ethanol consumption and about 5% of adults end up with an alcohol use disorder (AUD). Many people with an AUD often find themselves in a cycle of binge, remission, and relapse.

Following ethanol consumption ethanol enters the bloodstream from the small intestine where it gets distributed to peripheral tissues. Ethanol in the bloodstream is cleared from the system by the liver. The primary …

The Identification Of Lxr-Dependent Pathways In The Dorsal Root Ganglia In Models Of Obesity, Nadia Elshareif

Master's Theses

Peripheral Neuropathy is characterized as injury to the peripheral nervous system. In terms of sensory neuropathy, metabolic syndrome is involved in chronic inflammation and ER stress pathways induced by lipid overload, leading to the structural and physiological damage of afferent sensory nerves. To protect the cell from lipid-induced ER stress, Liver X Receptors (LXRs) are sterol-activated nuclear transcription factors that are of particular interest due to its role in the regulation of lipid homeostasis, membrane phospholipids, and inflammation in metabolic tissues. Their role in the peripheral nervous system remains to be elucidated. LPCAT3, regulated by LXRs, has been shown to …

Advancing Our Understanding Of Mechanosensitive Microtubule Acetylation In Neurons, Margaret Earl Utgaard

Master's Theses

Stiffness is a signaling cue in the brain, and neuronal response to stiffness impacts development, injury and disease. Mechanotransduction is the process of cells interpreting and converting mechanical cues to biochemical signals. Tubulin acetylation increases microtubule stability and could be mechanosensitive. The impact of stiffness on tubulin acetylation and role of septins is the focus of this project.It was hypothesized that stiffer surfaces would increase tubulin acetylation. SH-SY5Y cells were plated on varying stiffness and the ratio of acetylated to alpha tubulin was measured using immunocytochemistry. This study found SH-SY5Y cells had the highest acetylation on hard surfaces. SH-SY5Y cells …

Characterization And Targeting Of Voltage-Gated Ion Channels In Meningioma Cell Lines, Erik White

Master's Theses

Meningiomas (MN) are primary brain tumors originating in the meningeal covering of the central nervous system. These tissues can evolve through familial inheritance (NF2, Cowden Syndrome, or Werner Syndrome) or sporadic mutations. The WHO categorizes MNs into three grades (I-III); Grade I contain benign tumors and Grade III the most aggressive. Increasing grade coincides with an increase in genetic diversity, making universal treatments difficult. MNs are typically treated with hydroxyurea (HU), but this chemotherapy agent has many adverse side effects, leading to research in less toxic options. This study uses ion channel antagonists for T- and L-type calcium channels using …

Characterizing A Putative Membrane Androgen Receptor In Glioma Cell Models, Emma Yuen

Master's Theses

The goal of this current research was to explore the role of a putative membraneandrogen receptor (AR) in modulating the viability of various models of glioma/astrocytoma, relative to normal (non-tumor) astrocytes. We hypothesized that binding to the membrane AR could enhance the sensitivity of glioma cells to toxic insult (i.e., the chemotherapeutic, Temozolomide, TMZ), while leaving “normal” astrocytes unscathed. Our data reveal that binding to the putative membrane AR sensitized C6 glioma cells to TMZ and the oxidative/metabolic insult, iodoacetic acid (IAA). And while there was some evidence that binding to the membrane AR could enhance the effect of TMZ …

The Effect Of Gonadal Steroids Following Repeat Mild Traumatic Brain Injury On Anxiety-Like Behaviors In Rats, Trevor Nykamp

Master's Theses

Traumatic brain injury (TBI) affects millions of people in the U.S. each year. This thesis worked to address anxiety, a common emotional symptom following TBI, by utilizing a five-hit repeat mild TBI (rmTBI) experimental model. First, changes in gonadal status following injury and the severity of anxiety symptoms experienced were investigated. Our data revealed that suppressed testosterone levels following rmTBI resulted in significantly more anxiety-like behaviors across several observational variables. Even more, some of these behaviors were reduced by providing testosterone supplementation immediately following injury.Another goal of this work was to investigate the role of mitochondrial dysfunction, measured by COX4i1 …

Gephyrin-Lacking Pv Synapses On Neocortical Pyramidal Neurons, Dika A. Kuljis, Kristina D. Micheva, Ajit Ray, Waja Wegner, Ryan Bowman, Daniel V. Madison, Katrin I. Willig, Alison L. Barth

Biology Faculty Publications

Gephyrin has long been thought of as a master regulator for inhibitory synapses, acting as a scaffold to organize γ-aminobutyric acid type A receptors (GABA_ARs) at the post-synaptic density. Accordingly, gephyrin immunostaining has been used as an indicator of inhibitory synapses; despite this, the pan-synaptic localization of gephyrin to specific classes of inhibitory synapses has not been demonstrated. Genetically encoded fibronectin intrabodies generated with mRNA display (FingRs) against gephyrin (Gephyrin.FingR) reliably label endogenous gephyrin, and can be tagged with fluorophores for comprehensive synaptic quantitation and monitoring. Here we investigated input- and target-specific localization of gephyrin at a defined …

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 …

Interclass Gpcr Heteromerization Affects Localization And Trafficking, Rudy Toneatti

Theses and Dissertations

Class A serotonin (5-hydroxytryptamine) 2A (5-HT_2AR) and class C metabotropic glutamate 2 receptors (mGluR2) are seven transmembrane receptors (7TMRs or G protein-coupled receptors – GPCRs) involved in multiple neuropsychiatric disorders including schizophrenia. Previous findings from our laboratory reported that 5-HT_2AR and mGluR2 are dysregulated in the prefrontal cortex of patients suffering from this psychiatric condition, although 5-HT_2AR’s expression was recovered in antipsychotic-medicated patients. Genome-wide association studies on schizophrenia reported that endosomal trafficking that regulates cell surface abundance of another 7TMR implicated in this disease (dopamine D2 receptor) can be altered. Ligand-activated receptors, including the …

Evaluating Neuromuscular Function Of The Biceps Brachii After Spinal Cord Injury: Assessment Of Voluntary Activation And Motor Evoked Potential Input-Output Curves Using Transcranial Magnetic Stimulation, Thibault Roumengous

Theses and Dissertations

Activation of upper limb muscles is important for independent living after cervical spinal cord injury (SCI) that results in tetraplegia. An emerging, non-invasive approach to address post-SCI muscle weakness is modulation of the nervous system. A long-term goal is to develop neuromodulation techniques to reinnervate (i.e. resupply nerve to) muscle fiber and thereby increase muscle function in individuals with tetraplegia. Towards this goal, developing monitoring techniques to quantify neuromuscular function is needed to better direct neurorehabilitation. Assessment of voluntary activation (VA) is a promising approach because the location of the stimulus can be applied cortically using transcranial magnetic stimulation (TMS) …

The Role Of Glt-1 Signaling In Oligodendrocytes During Development And Myelin Repair, Elizabeth Thomason

Theses and Dissertations

The differentiation of oligodendrocyte progenitor cells (OPCs) into myelinating oligodendrocytes (OLGs) requires an increase in the complexity of process morphology, alterations in membrane trafficking, and the production of myelin proteins. Branching and process extension have already been shown to follow glutamate signaling through OLG-expressed excitatory amino acid transporters (EAATs), mostly via GLT-1. It is of note that glutamate homeostasis often goes awry in multiple sclerosis (MS), the main demyelinating disease in humans. Thus, we have sought to gain an understanding of the role that GLT-1 plays under the myelination and remyelination conditions that arise during natural development of OLGs and …

Rapid Golgi Stain For Dendritic Spine Visualization In Hippocampus And Prefrontal Cortex, Maya Frankfurt, Rachel E. Bowman

Psychology Faculty Publications

Golgi impregnation, using the Golgi staining kit with minor adaptations, is used to impregnate dendritic spines in the rat hippocampus and medial prefrontal cortex. This technique is a marked improvement over previous methods of Golgi impregnation because the premixed chemicals are safer to use, neurons are consistently well impregnated, there is far less background debris, and for a given region, there are extremely small deviations in spine density between experiments. Moreover, brains can be accumulated after a certain point and kept frozen until further processing. Using this method any brain region of interest can be studied. Once stained and cover …