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Micrornas Are Necessary For Bmp-7-Induced Dendritic Growth In Cultured Rat Sympathetic Neurons, Vidya Chandrasekaran 2019 Saint Mary's College of California

Micrornas Are Necessary For Bmp-7-Induced Dendritic Growth In Cultured Rat Sympathetic Neurons, Vidya Chandrasekaran

Vidya Chandrasekaran

Neuronal connectivity is dependent on size and shape of the dendritic arbor. However, mechanisms controlling dendritic arborization, especially in the peripheral nervous system, are not completely understood. Previous studies have shown that bone morphogenetic proteins (BMPs) are important initiators of dendritic growth in peripheral neurons. In this study, we examined the hypothesis that post-transcriptional regulation mediated by microRNAs (miRNAs) is necessary for BMP-7-induced dendritic growth in these neurons. To examine the role of miRNAs in BMP-7-induced dendritic growth, microarray analyses was used to profile miRNA expression in cultured sympathetic neurons from the superior cervical ganglia of embryonic day 21 rat ...


Hyaluronan At The Brain-Environment Interface, Donald M. Thevalingam 2019 The Graduate Center, City University of New York

Hyaluronan At The Brain-Environment Interface, Donald M. Thevalingam

All Dissertations, Theses, and Capstone Projects

Hyaluronan (HA; Hyaluronic Acid), a primary scaffolding component of the brain extracellular matrix, serves as an integral structural component to the brain extracellular space (ECS). The fossorial African naked mole-rat (Heterocephalus glaber; NM-R), a mammal which lives in a low-oxygen environment and is capable of tolerating hypoxia and hypercapnia, has been shown to synthesize and sustain a unique high-molecular-mass variant of hyaluronan macromolecule (HMM-HA). This body of work highlights HA’s role in mediating the interplay between brain ECM composition, ECS structure, and cell viability.

Here we employ the NM-R as a unique animal model to observe the role of ...


Distributions Of Hypothalamic Neuron Populations Co-Expressing Tyrosine Hydroxylase And The Vesicular Gaba Transporter In The Mouse., Kenichiro Negishi, Mikayla A. Payant, Kayla S. Schumacker, Gabor Wittman, Rebecca M. Butler, Ronald M. Lechan, Harry W. M. Steinbusch m, Arshad M. Khan, Melissa J. Chee 2019 Carleton University

Distributions Of Hypothalamic Neuron Populations Co-Expressing Tyrosine Hydroxylase And The Vesicular Gaba Transporter In The Mouse., Kenichiro Negishi, Mikayla A. Payant, Kayla S. Schumacker, Gabor Wittman, Rebecca M. Butler, Ronald M. Lechan, Harry W. M. Steinbusch M, Arshad M. Khan, Melissa J. Chee

Arshad M. Khan, Ph.D.

No abstract provided.


Assessing The Role Of Drosophila Melanogaster Neuroligin 3 On Social Spacing And Climbing Behaviour, J. Wesley Robinson 2019 The University of Western Ontario

Assessing The Role Of Drosophila Melanogaster Neuroligin 3 On Social Spacing And Climbing Behaviour, J. Wesley Robinson

Electronic Thesis and Dissertation Repository

Autism spectrum disorders can be clinically defined in part by impairments of social interactions. Social interactions can be modeled in Drosophila melanogaster with behaviours such as social spacing. Here, I examined the effects of autism-related gene neuroligin 3 on fly social spacing. I hypothesized if neuroligin 3 is mutated or gene expression is targeted for knockdown, then flies will have altered social space in males and females at different ages. Using the social space assay, I found that different mutations to neuroligin 3 change the fly’s behavior, in a mutation and sex-specific manner. Using an antibody against Nlg3, I ...


Modulation Of Actin Polymerization Affects Nucleocytoplasmic Transport In Multiple Forms Of Amyotrophic Lateral Sclerosis, Anthony Giampetruzzi, Eric W. Danielson, Valentina Gumina, Maryangel Jeon, Sivakumar Boopathy, Robert H. Brown Jr., Antonia Ratti, John E. Landers, Claudia Fallini 2019 University of Massachusetts Medical School

Modulation Of Actin Polymerization Affects Nucleocytoplasmic Transport In Multiple Forms Of Amyotrophic Lateral Sclerosis, Anthony Giampetruzzi, Eric W. Danielson, Valentina Gumina, Maryangel Jeon, Sivakumar Boopathy, Robert H. Brown Jr., Antonia Ratti, John E. Landers, Claudia Fallini

Open Access Articles

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease of unknown etiology. Although defects in nucleocytoplasmic transport (NCT) may be central to the pathogenesis of ALS and other neurodegenerative diseases, the molecular mechanisms modulating the nuclear pore function are still largely unknown. Here we show that genetic and pharmacological modulation of actin polymerization disrupts nuclear pore integrity, nuclear import, and downstream pathways such as mRNA post-transcriptional regulation. Importantly, we demonstrate that modulation of actin homeostasis can rescue nuclear pore instability and dysfunction caused by mutant PFN1 as well as by C9ORF72 repeat expansion, the most common mutation in ALS patients ...


Development Of An Imaging Analysis Algorithm For Fluorescence-Based High Content Screening In Parkinson’S Disease, Ryan Arlinghaus 2019 Purdue University

Development Of An Imaging Analysis Algorithm For Fluorescence-Based High Content Screening In Parkinson’S Disease, Ryan Arlinghaus

The Journal of Purdue Undergraduate Research

No abstract provided.


Optimizing Crispr/Cas9 For Gene Silencing Of Sod1 In Mouse Models Of Als, Zachary C. Kennedy 2019 University of Massachusetts Medical School

Optimizing Crispr/Cas9 For Gene Silencing Of Sod1 In Mouse Models Of Als, Zachary C. Kennedy

GSBS Dissertations and Theses

Mutations in the SOD1 gene are the best characterized genetic cause of amyotrophic lateral sclerosis (ALS) and account for ~20% of inherited cases and 1-3% of sporadic cases. The gene-editing tool Cas9 can silence mutant genes that cause disease, but effective delivery of CRISPR-Cas9 to the central nervous system (CNS) remains challenging. Here, I developed strategies using canonical Streptococcus pyogenes Cas9 to silence SOD1. In the first strategy, I demonstrate effectiveness of systemic delivery of guide RNA targeting SOD1 to the CNS in a transgenic mouse model expressing human mutant SOD1 and Cas9. Silencing was observed in both the brain ...


The Functional Conservation Of Frazzled In Insects, Benjamin Wadsworth 2019 University of Arkansas, Fayetteville

The Functional Conservation Of Frazzled In Insects, Benjamin Wadsworth

Theses and Dissertations

Axons in the developing embryo receive and react to signals that direct their growth to reach target tissues at specified locations. The signal pathways that direct midline crossing of axons during embryonic development have been comprehensively examined in the past years using the Drosophila ventral nerve cord or the spinal cord as a model system. A number of these signaling mechanisms are conserved, however disparities have been found between species in general strategy or the molecular signals controlling the response of axons to guidance cues.

The Netrin-Frazzled pathway has been shown to aid in midline crossing of axons in the ...


The Functional And Structural Analysis Of Drosophila Robo2 In Axon Guidance, LaFreda Janae Howard 2019 University of Arkansas, Fayetteville

The Functional And Structural Analysis Of Drosophila Robo2 In Axon Guidance, Lafreda Janae Howard

Theses and Dissertations

In animals with complex nervous systems such as mammals and insects, signaling pathways are responsible for guiding axons to their appropriate synaptic targets. Importantly, when this process is not successful during the development of an organism, outcomes include catastrophes such as human neurological diseases and disorders. It is vital to determine the underlying causes of such diseases by understanding the development of the nervous system. There are many pathways that have been identified to play a role in this, however, we lack an understanding of how these pathways can promote such diverse outcomes in different populations of neurons. These pathways ...


Intron And Small Rna Localization In Mammalian Neurons, Harleen Saini 2019 University of Massachusetts Medical School

Intron And Small Rna Localization In Mammalian Neurons, Harleen Saini

GSBS Dissertations and Theses

RNA molecules are diverse in form and function. They include messenger RNAs (mRNAs) that are templates for proteins, splice products such as introns that can generate functional noncoding RNAs, and a slew of smaller RNAs such as transfer RNAs (tRNAs) that help decode mRNAs into proteins. RNAs can show distinct patterns of subcellular localization that play an important role in protein localization. However, RNA distribution in cells is incompletely understood, with prior studies focusing primarily on RNAs that are long (>200 nucleotides), fully processed, and polyadenylated. We examined the distribution of RNAs in neurons. Neuronal compartments can be separated by ...


Nonnative Structure In A Peptide Model Of The Unfolded State Of Sod1: Implications For Als-Linked Aggregation, Noah R. Cohen, Jill A. Zitzewitz, Osman Bilsel, C. Robert Matthews 2019 University of Massachusetts Medical School

Nonnative Structure In A Peptide Model Of The Unfolded State Of Sod1: Implications For Als-Linked Aggregation, Noah R. Cohen, Jill A. Zitzewitz, Osman Bilsel, C. Robert Matthews

Open Access Articles

Dozens of mutations throughout the sequence of the gene encoding superoxide dismutase 1 (SOD1) have been linked to toxic protein aggregation in the neurodegenerative disease amyotrophic lateral sclerosis (ALS). A parsimonious explanation for numerous genotypes resulting in a common phenotype would be mutation-induced perturbation of the folding free-energy surface that increases the populations of high-energy states prone to aggregation. The absence of intermediates in the folding of monomeric SOD1 suggests that the unfolded ensemble is a potential source of aggregation. To test this hypothesis, here we dissected SOD1 into a set of peptides end-labeled with FRET probes to model the ...


Co-Option Of Neurotransmitter Signaling For Inter-Organismal Communication In C. Elegans, Christopher D. Chute, Elizabeth M. DiLoreto, Ying K. Zhang, Douglas K. Reilly, Diego Rayes, Veronica L. Coyle, Hee June Choi, Mark J. Alkema, Frank C. Schroeder, Jagan Srinivasan 2019 Worcester Polytechnic Institute

Co-Option Of Neurotransmitter Signaling For Inter-Organismal Communication In C. Elegans, Christopher D. Chute, Elizabeth M. Diloreto, Ying K. Zhang, Douglas K. Reilly, Diego Rayes, Veronica L. Coyle, Hee June Choi, Mark J. Alkema, Frank C. Schroeder, Jagan Srinivasan

Neurobiology Publications

Biogenic amine neurotransmitters play a central role in metazoan biology, and both their chemical structures and cognate receptors are evolutionarily conserved. Their primary roles are in cell-to-cell signaling, as biogenic amines are not normally recruited for communication between separate individuals. Here, we show that in the nematode C. elegans, a neurotransmitter-sensing G protein-coupled receptor, TYRA-2, is required for avoidance responses to osas#9, an ascaroside pheromone that incorporates the neurotransmitter, octopamine. Neuronal ablation, cell-specific genetic rescue, and calcium imaging show that tyra-2 expression in the nociceptive neuron, ASH, is necessary and sufficient to induce osas#9 avoidance. Ectopic expression in ...


Molecular Specialization Of Gabaergic Synapses On The Soma And Axon In Cortical And Hippocampal Circuit Function And Dysfunction, April Contreras, Dustin J. Hines, Rochelle M. Hines 2019 University of Nevada, Las Vegas

Molecular Specialization Of Gabaergic Synapses On The Soma And Axon In Cortical And Hippocampal Circuit Function And Dysfunction, April Contreras, Dustin J. Hines, Rochelle M. Hines

Psychology Faculty Publications

The diversity of inhibitory interneurons allows for the coordination and modulation of excitatory principal cell firing. Interneurons that release GABA (γ-aminobutyric acid) onto the soma and axon exert powerful control by virtue of proximity to the site of action potential generation at the axon initial segment (AIS). Here, we review and examine the cellular and molecular regulation of soma and axon targeting GABAergic synapses in the cortex and hippocampus. We also describe their role in controlling network activity in normal and pathological states. Recent studies have demonstrated a specific role for postsynaptic dystroglycan in the formation and maintenance of cholecystokinin ...


Investigation Of Even-Skipped, A Developmentally-Regulated Gene Controlling Neural Segmentation In Dragonflies, Kathryn Bangser 2019 Union College - Schenectady, NY

Investigation Of Even-Skipped, A Developmentally-Regulated Gene Controlling Neural Segmentation In Dragonflies, Kathryn Bangser

Honors Theses

A comprehensive understanding of the genetic mechanisms underlying pattern formation and neurogenesis is necessary in order to trace the evolutionary history of insect embryogenesis.

One of the most important processes of embryogenesis is the organized pattern formation that allows for proper body segmentation and neural development. Proper segmentation, which relies on a series of specific gene expressions, is necessary for the development of an operational nervous system. Even-skipped (eve), one such regulatory gene, has been studied extensively in certain model organisms, and theories regarding the evolution of its functional role could be further elucidated by visualizing its expression in adult ...


Novel Characterization Of The Role Of Orthologous Xap5 In Caenorhabditis Elegans, Nabor Vazquez 2019 Lawrence University

Novel Characterization Of The Role Of Orthologous Xap5 In Caenorhabditis Elegans, Nabor Vazquez

Lawrence University Honors Projects

Cilia are one of the oldest and most well conserved cellular organelles. Cilia provide an essential role in cellular locomotion, fluid regulation, and are a site for signal transduction pathways involved in sensation. A new study suggests that XAP5 is a transcription factor in a unicellular organism, Chlamydomonas reinhardtii, which regulates gene expression needed for proper cilium assembly. Our study investigates the conservation of the role of XAP5 in a multicellular system, Caenorhabditis elegans. Alignments between protein, coding region, and promoter sequences for XAP5 orthologs from related species show a good conservation in DNA and protein sequences. As part of ...


Towards A Better Understanding Of Temporomandibular Disorder, Jessica R. Cox 2019 MIssouri State University

Towards A Better Understanding Of Temporomandibular Disorder, Jessica R. Cox

MSU Graduate Theses

Results from the OPPERA study provided evidence that risk factors such as neck muscle tension, prolonged jaw opening, and female gender increase the likelihood of developing temporomandibular joint disorders (TMJD), which are prevalent, debilitating orofacial pain conditions. Peripheral and central sensitization, which mediate a lowering of the stimulus required for pain signaling, are implicated in the underlying pathology of chronic TMJD. The goal of my study was to investigate cellular changes in the expression of proteins associated with the development of central sensitization. Female Sprague-Dawley rats were injected with complete Freund’s adjuvant in the upper trapezius muscles to promote ...


Mechanisms Of Calcium-Dependent Neurotransmission In Photoreceptors, Justin J. Grassmeyer 2019 University of Nebraska Medical Center

Mechanisms Of Calcium-Dependent Neurotransmission In Photoreceptors, Justin J. Grassmeyer

Theses & Dissertations

Rod and cone photoreceptors initiate vision by transforming light into graded membrane voltage changes that in turn dictate the rate of continuous Ca2+-dependent neurotransmission to postsynaptic neurons. Continuous release relies on synaptic ribbons at photoreceptor active zones, which organize exocytotic proteins and deliver vesicles to release sites near voltage-gated Ca2+ channels. Individual cones possess multiple ribbon synapses at which they contact postsynaptic neurons. We examined heterogeneity in signaling at individual ribbon synapses in salamander cones by measuring the voltage dependence of Ca2+ currents (ICa) and Ca2+ influx at individual ribbon release sites. Ca2 ...


Notch Inhibitors And The Bet Inhibitor Jq-1 Decrease The Growth Of Primary Tumor Cells Derived From A Novel Mouse Model Of C11orf95-Rela Induced Brain Tumor, Ericka Randazzo, Jesse Dunnack, Justin Fang, Joseph LoTurco PhD 2019 University of Connecticut - Storrs

Notch Inhibitors And The Bet Inhibitor Jq-1 Decrease The Growth Of Primary Tumor Cells Derived From A Novel Mouse Model Of C11orf95-Rela Induced Brain Tumor, Ericka Randazzo, Jesse Dunnack, Justin Fang, Joseph Loturco Phd

University Scholar Projects

Brain tumors are the most common childhood solid malignancy, and because of remarkable advances in treating many cancers outside of the brain, they have become the leading cause of cancer mortality in children. Ependymomas are a class of brain tumors which can be further subdivided into three groups based upon their location and genetic features. Of the three classes, supratentorial ependymomas are the only subgroup known to be marked by an oncogenic driver gene, which consists of a fusion mutation between the C11orf95 and RELA genes. C11orf95-RELA positive tumors are the most aggressive and lethal of ...


Quantifying Expression Of Interneuron Subtype Markers For Dlx-2 Transfected Ng2 Cells, Timothy Nolan 2019 University of Connecticut

Quantifying Expression Of Interneuron Subtype Markers For Dlx-2 Transfected Ng2 Cells, Timothy Nolan

Honors Scholar Theses

Neurons are a post-mitotic cell population, and therefore, they are not able to regenerate in vivo after a traumatic injury. Because inhibitory GABAergic interneurons and oligodendrocyte precursor cells (OPCs) are derived from the same precursor, recent studies have focused on transforming these OPCs into GABAergic neurons. However, there are different types of GABAergic interneurons that have different electrophysiological responses, which can lead to functional differences. The Nishiyama laboratory had already used a key gene in GABAergic interneuron and OPC differentiation, Distal-less homeobox 2 (Dlx-2), to transfect OPCs; early electrophysiology tests showed most of these transfected cells behaved like immature neurons ...


Glycine Receptor Expression Across Identified Retinal Ganglion Cell Types., Ian Scot Pyle 2019 University of Louisville

Glycine Receptor Expression Across Identified Retinal Ganglion Cell Types., Ian Scot Pyle

Electronic Theses and Dissertations

Retinal ganglion cells (RGCs) represent the culmination of all retinal signaling and their output forms the substrate for vision throughout the rest of the brain. About 40 different RGC types have been defined by differences in their visually evoked responses, morphology, and genetic makeup. These responses arise from interactions between inhibition and excitation throughout the retinal circuit (Franke et al., 2017; Masland, 2012; Sanes & Masland, 2015; Werblin, 2011). Unlike most other areas of the central nervous system (CNS), the retina utilizes both GABA and glycine inhibitory neurotransmitters to refine glutamatergic excitatory signals (Franke & Baden, 2017; Werblin, 2011; C. Zhang, Nobles, & McCall, 2015). Glycine receptors (GlyRs) are heteromers composed of a single β subunit and one of four α subunits, with a stoichiometry of 3β:2α (Grudzinska et al., 2005; Heinze, Harvey, Haverkamp, & Wassle, 2007; Lynch ...


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