Open Access. Powered by Scholars. Published by Universities.®

Molecular Biology Commons

Open Access. Powered by Scholars. Published by Universities.®

2016

Neuroscience and Neurobiology

Institution
Keyword
Publication
Publication Type

Articles 1 - 21 of 21

Full-Text Articles in Molecular Biology

Mitogen And Morphogen Signaling Dysregulation: Pathophysiological Influence In Pancreatic Cancer And Alzheimer’S Disease, Eric Cruz Dec 2016

Mitogen And Morphogen Signaling Dysregulation: Pathophysiological Influence In Pancreatic Cancer And Alzheimer’S Disease, Eric Cruz

Theses & Dissertations

Although the etiology of a particular disease will vary, there are genetic and epigenetic bottlenecks that frequently converge resulting in dysregulation of mitogenic and morphogenetic signaling. This propensity is acutely experienced in malignancy and neurodegenerative disease.

Here, we have first investigated the role of dysregulated signaling in the context of pancreatic cancer (PC). Morphogenetic signaling has been regarded as a pleiotropic pathway with the potential to promote and inhibit metastatic features. Our investigation of bone morphogenetic protein 2 (BMP-2), an archetypical member of the BMP superfamily, has revealed the presence of extracellular, intracellular, and long non-coding RNA products. Our findings ...


Characterization Of Vesicular Monoamine Transporter 2 And Its Role In Parkinson's Disease Pathogenesis Using Drosophila, Antonio Joel Tito Jr., Sheng Zhang Dec 2016

Characterization Of Vesicular Monoamine Transporter 2 And Its Role In Parkinson's Disease Pathogenesis Using Drosophila, Antonio Joel Tito Jr., Sheng Zhang

UT GSBS Dissertations and Theses (Open Access)

Parkinson’s disease (PD) is a progressive neurodegenerative disorder caused by the selective loss of the dopaminergic neurons in the Substantia nigra pars compacta region of the brain. PD is also the most common neurodegenerative disorder and the second most common movement disorder. PD patients exhibit the cardinal symptoms, including tremor of the extremities, rigidity, slowness of movement, and postural instability, after 70-80% of DA neurons degenerate. It is, therefore, imperative to elucidate the underlying mechanisms involved in the selective degeneration of DA neurons. Although increasing numbers of PD genes have been identified, why these largely widely expressed genes ...


Rna Sequencing Analysis Of The Developing Chicken Retina, Christophe Langouet-Astrie*, Annamarie Meinsen*, Emily R. Grunwald*, Stephen Turner, Raymond A. Enke Nov 2016

Rna Sequencing Analysis Of The Developing Chicken Retina, Christophe Langouet-Astrie*, Annamarie Meinsen*, Emily R. Grunwald*, Stephen Turner, Raymond A. Enke

Ray Enke Ph.D.

RNA sequencing transcriptome analysis using massively parallel next generation sequencing technology provides the capability to understand global changes in gene expression throughout a range of tissue samples. Development of the vertebrate retina requires complex temporal orchestration of transcriptional activation and repression. The chicken embryo (Gallus gallus) is a classic model system for studying developmental biology and retinogenesis. Existing retinal transcriptome projects have been critical to the vision research community for studying aspects of murine and human retinogenesis, however, there are currently no publicly available data sets describing the developing chicken retinal transcriptome. Here we used Illumina RNA sequencing (RNA-seq) analysis ...


Design Of Novel Ion Channel Modulators, Vladimir Yarov-Yarovoy Nov 2016

Design Of Novel Ion Channel Modulators, Vladimir Yarov-Yarovoy

Science Seminar Series

Function and modulation of neuronal sodium channels are critical for the neuromodulation of electrical excitability and synaptic transmission in neurons - the basis for many aspects of signal transduction, learning, memory and physiological regulation. Mutations in neuronal voltage-gated sodium channel genes are responsible for various human neurological disorders. Furthermore, human neuronal voltage-gated sodium channels are primary targets of therapeutic drugs used as local anesthetics and for treatment of neurological and cardiac disorders. Yarov-Yarovoy's lab is working on rational design of novel therapeutically useful blockers of voltage-gated sodium channels for treatment of pain and epilepsy. Serious, chronic pain affects at least ...


Exosome-Mediated Delivery Of Hydrophobically Modified Sirna For Huntingtin Mrna Silencing, Marie C. Didiot, Lauren M. Hall, Andrew H. Coles, Reka A. Haraszti, Bruno M. D. C. Godinho, Kathryn O. Chase, Socheata Ly, Julia F. Alterman, Matthew R. Hassler, Dimas Echeverria, Neil Aronin, Anastasia Khvorova Oct 2016

Exosome-Mediated Delivery Of Hydrophobically Modified Sirna For Huntingtin Mrna Silencing, Marie C. Didiot, Lauren M. Hall, Andrew H. Coles, Reka A. Haraszti, Bruno M. D. C. Godinho, Kathryn O. Chase, Socheata Ly, Julia F. Alterman, Matthew R. Hassler, Dimas Echeverria, Neil Aronin, Anastasia Khvorova

RNA Therapeutics Institute Publications

Delivery represents a significant barrier to the clinical advancement of oligonucleotide therapeutics for the treatment of neurological disorders, such as Huntington's disease. Small, endogenous vesicles known as exosomes have the potential to act as oligonucleotide delivery vehicles, but robust and scalable methods for loading RNA therapeutic cargo into exosomes are lacking. Here, we show that hydrophobically modified small interfering RNAs (hsiRNAs) efficiently load into exosomes upon co-incubation, without altering vesicle size distribution or integrity. Exosomes loaded with hsiRNAs targeting Huntingtin mRNA were efficiently internalized by mouse primary cortical neurons and promoted dose-dependent silencing of Huntingtin mRNA and protein. Unilateral ...


Overcoming Toxicity From Transgene Overexpression Through Vector Design In Aav Gene Therapy For Gm2 Gangliosidoses, Diane L. Golebiowski Sep 2016

Overcoming Toxicity From Transgene Overexpression Through Vector Design In Aav Gene Therapy For Gm2 Gangliosidoses, Diane L. Golebiowski

GSBS Dissertations and Theses

GM2 gangliosidoses are a family of lysosomal storage disorders that include both Tay-Sachs and Sandhoff diseases. These disorders result from deficiencies in the lysosomal enzyme β-N-acetylhexosaminidase (HexA). Impairment of HexA leads to accumulation of its substrate, GM2 ganglioside, in cells resulting in cellular dysfunction and death. There is currently no treatment for GM2 gangliosidoses. Patients primarily present with neurological dysfunction and degeneration. Here we developed a central nervous system gene therapy through direct injection that leads to long-term survival in the Sandhoff disease mouse model. We deliver an equal mixture of AAVrh8 vectors that encode for the two subunits (α ...


Cal And Magi Pdz Protein Regulation Of Crfr1 And 5-Ht2ar Trafficking And Signaling, Maha Mahmoud Hammad Aug 2016

Cal And Magi Pdz Protein Regulation Of Crfr1 And 5-Ht2ar Trafficking And Signaling, Maha Mahmoud Hammad

Electronic Thesis and Dissertation Repository

PDZ (PSD95/Disc Large/Zona Occludens) domain-containing proteins are scaffolding proteins that play important roles in regulating the activity of G protein-coupled receptors. Corticotropin Releasing Factor Receptor 1 (CRFR1) and Serotonin 2A Receptor (5-HT2AR) are two GPCRs that are commonly associated with mental disorders. Both receptors also contain a class I PDZ-binding motif at the carboxyl terminal tail. In the first chapter, we investigate the effects of CAL (CFTR-associated ligand) on regulating the trafficking and signaling of CRFR1. We demonstrate a role for CAL in inhibiting CRFR1 endocytosis, cell surface expression, and CRF-mediated ERK1/2 signaling via the ...


Docosahexaenoic Acid Conjugation Enhances Distribution And Safety Of Sirna Upon Local Administration In Mouse Brain, Mehran Nikan, Maire F. Osborn, Andrew H. Coles, Bruno M. D. C. Godinho, Lauren M. Hall, Reka A. Haraszti, Dimas Echeverria, Neil Aronin, Matthew R. Hassler, Anastasia Khvorova Aug 2016

Docosahexaenoic Acid Conjugation Enhances Distribution And Safety Of Sirna Upon Local Administration In Mouse Brain, Mehran Nikan, Maire F. Osborn, Andrew H. Coles, Bruno M. D. C. Godinho, Lauren M. Hall, Reka A. Haraszti, Dimas Echeverria, Neil Aronin, Matthew R. Hassler, Anastasia Khvorova

RNA Therapeutics Institute Publications

The use of siRNA-based therapies for the treatment of neurodegenerative disease requires efficient, nontoxic distribution to the affected brain parenchyma, notably the striatum and cortex. Here, we describe the synthesis and activity of a fully chemically modified siRNA that is directly conjugated to docosahexaenoic acid (DHA), the most abundant polyunsaturated fatty acid in the mammalian brain. DHA conjugation enables enhanced siRNA retention throughout both the ipsilateral striatum and cortex following a single, intrastriatal injection (ranging from 6-60 mug). Within these tissues, DHA conjugation promotes internalization by both neurons and astrocytes. We demonstrate efficient and specific silencing of Huntingtin mRNA expression ...


Exploring The Relationship Between Behaviour And Neurochemistry In The Polyphenic Spider, Anelosimus Studiosus (Araneae: Theridiidae), Jennifer B. Price Aug 2016

Exploring The Relationship Between Behaviour And Neurochemistry In The Polyphenic Spider, Anelosimus Studiosus (Araneae: Theridiidae), Jennifer B. Price

Electronic Theses and Dissertations

The importance of social behaviour is evident in human society, but there are both costs and benefits associated with cooperation and sociality throughout the animal kingdom. At what point do the benefits outweigh the costs, and when do selective pressures favour sociality and colonization over solitude and independence? To investigate these questions, we have focused on an anomalous species of spider, Anelosimus studiosus, also known now as the northern social spider. Throughout its broad range, A. studiosus is solitary and aggressive, but recently, colonies of cooperative and social individuals have been observed at northern latitudes. This leads to two research ...


The Role Of Daf-19 In Non-Ciliated Neurons: How Is Neural Development Regulated By Different Daf-19 Isoforms?, Zabdiel Ek Vazquez Jun 2016

The Role Of Daf-19 In Non-Ciliated Neurons: How Is Neural Development Regulated By Different Daf-19 Isoforms?, Zabdiel Ek Vazquez

Lawrence University Honors Projects

A degenerative disease-like phenotype, specifically reduction in synaptic protein levels in adult worms, is correlated with loss-of-function of the only RFX transcription factor gene, daf-19, in C. elegans. This gene encodes four known transcription factor isoforms, two of which are correlated with particular functions. The DAF-19C isoform activates genes responsible for cilia development, while DAF-19M is needed for cilia specification in males. A comparison of the transcriptome of daf-19 null and isogenic wild type adult worms suggests both positive and negative regulation of gene expression is correlated with the presence of DAF-19 proteins. We have assessed DAF-19 regulation of gene ...


The Effects Of Chronic Partial Sleep Deprivation And Chronic Voluntary Alcohol Consumption On Δfos B Accumulation, Kristian Ponder May 2016

The Effects Of Chronic Partial Sleep Deprivation And Chronic Voluntary Alcohol Consumption On Δfos B Accumulation, Kristian Ponder

Masters Theses

The present study explores the relation between sleep restriction and alcohol use and the neural substrates that result from chronic behaviors. Accumulation of the transcription factors ΔFosB is suggested as a possible outcome of chronic behaviors, such as addiction. Sleep is discussed as possible mediating factor in the relationship between ΔFosB and chronic alcohol consumption. There were four experimental groups in this study: Control (C), Sleep Deprivation only (SD), Alcohol Exposure only (AO), and both sleep deprivation and alcohol exposure (B). Levels of ΔFosB accumulation in the Nucleus Accumbens (NAc) revealed a significant main effect of sleep deprivation, but no ...


Reciprocal Autoregulation By Nfi Occupancy And Etv1 Promotes The Developmental Expression Of Dendrite-Synapse Genes In Cerebellar Granule Neurons, Baojin Ding, John W. Cave, Paul R. Dobner, Debra Mullikin-Kilpatrick, Marina Bartzokis, Hong Zhu, Chi-Wing Chow, Richard M. Gronostajski, Daniel Lee Kilpatrick May 2016

Reciprocal Autoregulation By Nfi Occupancy And Etv1 Promotes The Developmental Expression Of Dendrite-Synapse Genes In Cerebellar Granule Neurons, Baojin Ding, John W. Cave, Paul R. Dobner, Debra Mullikin-Kilpatrick, Marina Bartzokis, Hong Zhu, Chi-Wing Chow, Richard M. Gronostajski, Daniel Lee Kilpatrick

Open Access Articles

Nuclear Factor One (NFI) transcription factors regulate temporal gene expression required for dendritogenesis and synaptogenesis via delayed occupancy of target promoters in developing cerebellar granule neurons (CGNs). Mechanisms that promote NFI temporal occupancy have not been previously defined. We show here that the transcription factor ETV1 directly binds to and is required for expression and NFI occupancy of a cohort of NFI-dependent genes in CGNs maturing in vivo. Expression of ETV1 is low in early postnatal cerebellum and increases with maturation, mirroring NFI temporal occupancy of coregulated target genes. Precocious expression of ETV1 in mouse CGNs accelerated onset of expression ...


Axonal Transport And Life Cycle Of Mitochondria In Parkinson's Disease Model, Hyun Sung Apr 2016

Axonal Transport And Life Cycle Of Mitochondria In Parkinson's Disease Model, Hyun Sung

Open Access Dissertations

In neurons, normal distribution and selective removal of mitochondria are essential for preserving compartmentalized cellular function. Parkin, an E3 ubiquitin ligase associated with familial Parkinson’s disease, has been implicated in mitochondrial dynamics and removal. However, it is not clear how Parkin plays a role in mitochondrial turnover in vivo, and whether the mature neurons possess a compartmentalized Parkin-dependent mitochondrial life cycle. Using the live Drosophila nervous system, here, I investigate the involvement of Parkin in mitochondrial dynamics; organelle distribution, morphology and removal. Parkin deficient animals displayed less number of axonal mitochondria without disturbing organelle motility behaviors, morphology and metabolic ...


Excitatory Transmission Onto Agrp Neurons Is Regulated By Cjun Nh2-Terminal Kinase 3 In Response To Metabolic Stress, Santiago Vernia, Caroline Morel, Joseph C. Madara, Julie Cavanagh-Kyros, Tamera Barrett, Kathryn O. Chase, Norman J. Kennedy, Dae Young Jung, Jason K. Kim, Neil Aronin, Richard A. Flavell, Bradford B. Lowell, Roger J. Davis Feb 2016

Excitatory Transmission Onto Agrp Neurons Is Regulated By Cjun Nh2-Terminal Kinase 3 In Response To Metabolic Stress, Santiago Vernia, Caroline Morel, Joseph C. Madara, Julie Cavanagh-Kyros, Tamera Barrett, Kathryn O. Chase, Norman J. Kennedy, Dae Young Jung, Jason K. Kim, Neil Aronin, Richard A. Flavell, Bradford B. Lowell, Roger J. Davis

Davis Lab Publications

The cJun NH2-terminal kinase (JNK) signaling pathway is implicated in the response to metabolic stress. Indeed, it is established that the ubiquitously expressed JNK1 and JNK2 isoforms regulate energy expenditure and insulin resistance. However, the role of the neuron-specific isoform JNK3 is unclear. Here we demonstrate that JNK3 deficiency causes hyperphagia selectively in high fat diet (HFD)-fed mice. JNK3 deficiency in neurons that express the leptin receptor LEPRb was sufficient to cause HFD-dependent hyperphagia. Studies of sub-groups of leptin-responsive neurons demonstrated that JNK3 deficiency in AgRP neurons, but not POMC neurons, was sufficient to cause the hyperphagic response. These ...


Hpcnmf: A High-Performance Toolbox For Non-Negative Matrix Factorization, Karthik Devarajan, Guoli Wang Feb 2016

Hpcnmf: A High-Performance Toolbox For Non-Negative Matrix Factorization, Karthik Devarajan, Guoli Wang

COBRA Preprint Series

Non-negative matrix factorization (NMF) is a widely used machine learning algorithm for dimension reduction of large-scale data. It has found successful applications in a variety of fields such as computational biology, neuroscience, natural language processing, information retrieval, image processing and speech recognition. In bioinformatics, for example, it has been used to extract patterns and profiles from genomic and text-mining data as well as in protein sequence and structure analysis. While the scientific performance of NMF is very promising in dealing with high dimensional data sets and complex data structures, its computational cost is high and sometimes could be critical for ...


Messenger Rna Transport And Translation Regulated By The 3' Utrs Of Dendritic Mrnas And Abnormal Alternative Splicing Of Neuroligin1 In The Fmr1 Ko Mouse Hippocampus, Tianhui Zhu Feb 2016

Messenger Rna Transport And Translation Regulated By The 3' Utrs Of Dendritic Mrnas And Abnormal Alternative Splicing Of Neuroligin1 In The Fmr1 Ko Mouse Hippocampus, Tianhui Zhu

All Dissertations, Theses, and Capstone Projects

Fragile X Syndrome (FXS) is one of the most commonly inherited mental retardations. It is caused by the loss of functional fragile X mental retardation protein (FMRP). Loss of functional FMRP is the most widespread single-gene cause of autism. The most prominent phenotype of FXS patients is an IQ ranging from 20 to 70. FMRP is an RNA binding protein, widely expressed in almost all tissues and highly expressed in brain. As a RNA binding protein, 85-90 % of FMRP in the brain is associated with polyribosomes. Approximately 4 % of total mRNA is associated with FMRP, which functions in the stability ...


Identification Of Novel Molecular-Genetic Pathways Regulating The Development Of Subpallial Derivatives, David Tischfield Jan 2016

Identification Of Novel Molecular-Genetic Pathways Regulating The Development Of Subpallial Derivatives, David Tischfield

Publicly Accessible Penn Dissertations

The embryonic subpallium produces many different neuronal cell types present throughout the adult telencephalon, including striatal medium spiny neurons (MSN) and cortical interneurons. Dysfunction of either cell type leads to neurological and psychiatric disorders including schizophrenia, epilepsy, and Tourette’s syndrome. Thus, understanding the molecular pathways that regulate their development and function has important implications for understanding disease pathogenesis. This work describes novel methods and genetic factors that expand our ability to characterize the development and function of two major subpallial derivatives: cortical interneurons and striatal MSN. The first part of this thesis characterizes a novel enrichment method for producing ...


Multiple Roles Of Ret Signaling In Mechanosensory Neuron Development, Michael Scott Fleming Jan 2016

Multiple Roles Of Ret Signaling In Mechanosensory Neuron Development, Michael Scott Fleming

Publicly Accessible Penn Dissertations

Somatosensation is critical for interaction with the surrounding environment. Somatosensory stimuli are detected by primary somatosensory neurons of the dorsal root ganglia and trigeminal ganglia, which detect distinct classes of stimuli, such as temperature, pain, and pressure. In Chapters 2 and 3 of this thesis, we focus on rapidly adapting low-threshold mechanoreceptors (RALTMRs), which mediate the detection of light touch. RALTMRs are molecularly defined by the early embryonic expression of the receptor tyrosine kinase Ret. Ret is required for the development of central axonal projections of RALTMRs into the dorsal spinal cord. RET responds to the glial cell line-derived family ...


Contextual Insights Into The Rett Syndrome Transcriptome, Brian Scott Roosevelt Johnson Jan 2016

Contextual Insights Into The Rett Syndrome Transcriptome, Brian Scott Roosevelt Johnson

Publicly Accessible Penn Dissertations

Mutations in MECP2 are responsible for Rett syndrome (RTT), a severe X-linked neurological disorder characterized by loss of developmental milestones, intellectual disability and motor impairments. However, molecular insight into how these mutations affect the neuronal transcriptiome, disrupt neuronal function and contribute to RTT is impeded by the cellular heterogeneity of the mammalian brain. A comparison between gene expression changes in the striatum, hypothalamus, and cerebellum of MeCP2-null mice revealed that gene expression changes are distinct between different brain regions, which suggests that MeCP2 function should be understood in a cell type-dependent context. To accomplish this task, I generated and phenotypically ...


Prokineticin-2: A Novel Anti-Apoptotic And Anti-Inflammatory Signaling Protein In Parkinson’S Disease, Matthew Neal Jan 2016

Prokineticin-2: A Novel Anti-Apoptotic And Anti-Inflammatory Signaling Protein In Parkinson’S Disease, Matthew Neal

Graduate Theses and Dissertations

The mechanisms behind the development and progression of Parkinson’s disease (PD) are still not fully understood. Several pathophysiological mechanisms have been implicated in the progression of the disease including oxidative stress, mitochondrial dysfunction, excitotoxicity, protein aggregation, and neuroinflammation. Since current therapeutic options for PD treat only the symptoms without influencing disease progression, recent translational studies have focused on identifying factors that protect against putative pathophysiological mechanisms of PD. We show herein, that the chemokine-like signaling protein, Prokineticin-2 (PK2), is expressed and secreted at higher levels in dopaminergic neurons during the acute phase of inflammatory or neurotoxic stress. Furthermore, we ...


Linking Acetyl-Coa Metabolism And Histone Acetylation To Dynamic Gene Regulation In Yeast And Mouse Hippocampus, Philipp Mews Jan 2016

Linking Acetyl-Coa Metabolism And Histone Acetylation To Dynamic Gene Regulation In Yeast And Mouse Hippocampus, Philipp Mews

Publicly Accessible Penn Dissertations

A compelling body of evidence suggests an intimate relationship between metabolic state and chromatin regulation. This link is manifested in key metabolites that participate in biochemical pathways as intermediates, and function as cofactors to regulate chromatin modifying enzymes. Of particular interest is the metabolite acetyl-CoA, given its central role as an intermediate of cellular energy metabolism and key determinant of all histone acetylation. How nuclear acetyl-CoA levels are regulated to, in turn, control histone acetylation is under intense investigation, and holds promise for increased understanding of the molecular mechanisms adapting gene expression to internal and external stimuli. We studied the ...