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Rare And Low Frequency Genomic Variants Impacting Neuronal Functions Modify The Dup7q11.23 Phenotype, Farah Qaiser, Yue Yin, Carolyn B. Mervis, Colleen A. Morris, Bonita P. Klein-Tasman, Elaine Tam, Lucy R. Osborne, Ryan K.C. Yuen 2021 University of Toronto

Rare And Low Frequency Genomic Variants Impacting Neuronal Functions Modify The Dup7q11.23 Phenotype, Farah Qaiser, Yue Yin, Carolyn B. Mervis, Colleen A. Morris, Bonita P. Klein-Tasman, Elaine Tam, Lucy R. Osborne, Ryan K.C. Yuen

School of Medicine Faculty Publications

© 2021, The Author(s). Background: 7q11.23 duplication (Dup7) is one of the most frequent recurrent copy number variants (CNVs) in individuals with autism spectrum disorder (ASD), but based on gold-standard assessments, only 19% of Dup7 carriers have ASD, suggesting that additional genetic factors are necessary to manifest the ASD phenotype. To assess the contribution of additional genetic variants to the Dup7 phenotype, we conducted whole-genome sequencing analysis of 20 Dup7 carriers: nine with ASD (Dup7-ASD) and 11 without ASD (Dup7-non-ASD). Results: We identified three rare variants of potential clinical relevance for ASD: a 1q21.1 microdeletion (Dup7-non-ASD) and two ...


Elucidating The Modulatory Role Of Dopamine In The C. Elegans Chemosensory Ash Neuron, Cory Kunkel 2021 California State University, San Bernardino

Elucidating The Modulatory Role Of Dopamine In The C. Elegans Chemosensory Ash Neuron, Cory Kunkel

Electronic Theses, Projects, and Dissertations

The neurotransmitter dopamine regulates chemosensory avoidance behavior in the model organism Caenorhabditis elegans. Avoidance behaviors are mediated by the polymodal ASH nociceptive sensory neurons, and behavioral avoidance of stimuli detected by ASH is less robust when dopamine signaling is impaired. We are investigating the neural response of the ASH neurons to various stimuli; our investigation includes the behavioral and physiological responses from the ASH neurons as dopamine signaling is manipulated to better understand the effects of dopamine on these sensory neurons. We hypothesize that dopamine plays a regulatory role on the ASH neurons, lessening the response of the ASH neuron ...


Sites Of Circadian Clock Neuron Plasticity Mediate Sensory Integration And Entrainment, Maria P. Fernand, Hannah L. Pettibone, Joseph T. Bogart, Casey J. Roell, Charles E. Davey, Ausra Pranevicius, Khang V. Huynh, Sara M. Lennox, Boyan Kostadinov, Orie T. Shafer 2021 CUNY Graduate Center

Sites Of Circadian Clock Neuron Plasticity Mediate Sensory Integration And Entrainment, Maria P. Fernand, Hannah L. Pettibone, Joseph T. Bogart, Casey J. Roell, Charles E. Davey, Ausra Pranevicius, Khang V. Huynh, Sara M. Lennox, Boyan Kostadinov, Orie T. Shafer

Publications and Research

Networks of circadian timekeeping in the brain display marked daily changes in neuronal morphology. In Drosophila melanogaster, the striking daily structural remodeling of the dorsal medial termini of the small ventral lateral neurons has long been hypothesized to mediate endogenous circadian timekeeping. To test this model, we have specifically abrogated these sites of daily neuronal remodeling through the reprogramming of neural development and assessed the effects on circadian timekeeping and clock outputs. Remarkably, the loss of these sites has no measurable effects on endogenous circadian timekeeping or on any of the major output functions of the small ventral lateral neurons ...


Targeting Ampa Receptor Modulation During Early Life Adversity: A Mediator For Threat Associated Memories, Roseanna M. Zanca 2021 The Graduate Center, City University of New York

Targeting Ampa Receptor Modulation During Early Life Adversity: A Mediator For Threat Associated Memories, Roseanna M. Zanca

Dissertations, Theses, and Capstone Projects

Early life adversity (ELA) is the exposure to a single or to multiple traumatic events before the age of 18 that go beyond the child’s coping. These adverse events are often exacerbated during adolescence particularly when cognitive performance is compromised. Adolescents who experienced ELA may show symptoms of post-traumatic stress disorder (PTSD), while not vividly recalling the early life trauma. These individuals show atypical connectivity between prefrontal-amygdala and hippocampus, all of which is associated with an increased risk of experiencing a traumatic event again later in life. While clinical research has increasingly stressed the importance in addressing the long-lasting ...


Expression And Subcellular Localization Of Circrnas Dysregulated Als That Are Encoded In Cytoskeletal Protein Genes, Asieh Alikhah 2021 The University of Western Ontario

Expression And Subcellular Localization Of Circrnas Dysregulated Als That Are Encoded In Cytoskeletal Protein Genes, Asieh Alikhah

Electronic Thesis and Dissertation Repository

Amyotrophic lateral sclerosis (ALS) is a fatal and progressive neurodegenerative disorder that causes the death of motor neurons. While alterations in the metabolism of RNA, including RNA-binding proteins have been linked to the pathogenesis of ALS, our understanding of the role of non-coding RNAs including circRNAs is less well developed. In this study, using a combination of fluorescence in situ hybridization (FISH) and immunofluorescence (IF) with markers of RNP granules, I investigated the effect of osmotic stress on the localization and expression of a selection of circRNAs whose expression is dysregulated in ALS. Alteration in the number of granules for ...


Modulation Of Gabaa Receptor By Neurosteroids And Protein Kinases In Health And Disease, Jaymin Jeong 2021 The University of Western Ontario

Modulation Of Gabaa Receptor By Neurosteroids And Protein Kinases In Health And Disease, Jaymin Jeong

Electronic Thesis and Dissertation Repository

γ-aminobutyric acid type A receptors (GABAA receptors) underlie the majority of inhibitory synaptic transmission in the brain. Modulation of GABAergic activity occurs in development and normal physiological functioning of the brain, and changes to GABAergic function has been implicated in numerous neurological disorders including epilepsy. Neurosteroids, metabolites of steroid hormones, and kinases are known to modulate GABAA receptor mediated currents in health and disease. This thesis aims to investigate the effects of kinases and neurosteroids on modulating GABAA receptor-mediated currents in cortical pyramidal cells and their effects on the piriform cortex (PCtx) circuit in naïve rats and ...


Identifying The Cell Composition And Clonal Diversity Of Supratentorial Ependymoma Using Single Cell Rna-Sequencing, James He 2021 University of Connecticut

Identifying The Cell Composition And Clonal Diversity Of Supratentorial Ependymoma Using Single Cell Rna-Sequencing, James He

Honors Scholar Theses

Ependymoma is a primary solid tumor of the central nervous system. Supratentorial ependymoma (ST-EPN), a subtype of ependymomas, is driven by an oncogenic fusion between the ZFTA and RELA genes in 70% of cases. We introduced this fusion into neural progenitor cells of mice embryos via in utero electroporation of a non-viral binary piggyBac transposon system containing ZFTA-RELA. From preliminary data in the LoTurco lab, inducing the expression of ZFTA-RELA into different neural progenitor cells produces tumors of varying lethality and cellular composition. To define the cellular composition and subclonal diversity of ST-EPN tumors, we used single cell RNA-sequencing to ...


Identifying The Cell Composition And Clonal Diversity Of Supratentorial Ependymoma Using Single Cell Rna-Sequencing, James He 2021 University of Connecticut

Identifying The Cell Composition And Clonal Diversity Of Supratentorial Ependymoma Using Single Cell Rna-Sequencing, James He

University Scholar Projects

Ependymoma is a primary solid tumor of the central nervous system. Supratentorial ependymoma (ST-EPN), a subtype of ependymomas, is driven by an oncogenic fusion between the ZFTA and RELA genes in 70% of cases. We introduced this fusion into neural progenitor cells of mice embryos via in utero electroporation of a non-viral binary piggyBac transposon system containing ZFTA-RELA. From preliminary data in the LoTurco lab, inducing the expression of ZFTA-RELA into different neural progenitor cells produces tumors of varying lethality and cellular composition. To define the cellular composition and subclonal diversity of ST-EPN tumors, we used single cell RNA-sequencing to ...


The Effects Of Mapk Signaling On The Development Of Cerebellar Granule Cells, Kerry Morgan 2021 University of Connecticut

The Effects Of Mapk Signaling On The Development Of Cerebellar Granule Cells, Kerry Morgan

Honors Scholar Theses

The granule cells are the most abundant neuronal type in the human brain. Rapid proliferation of granule cell progenitors results in dramatic expansion and folding of the cerebellar cortex during postnatal development. Mis-regulation of this proliferation process causes medulloblastoma, the most prevalent childhood brain tumor. In the developing cerebellum, granule cells are derived from Atoh1-expressing cells, which arise from the upper rhombic lip (the interface between the roof plate and neuroepithelium). In addition to granule cells, the Atoh1 lineage also gives rise to different types of neurons including cerebellar nuclei neurons. In the current study, I have investigated the ...


Mitochondrial Distribution Of Glycine Receptors In Motor Neuron Cell Lines, Katsiaryna Milashevich 2021 City University of New York (CUNY)

Mitochondrial Distribution Of Glycine Receptors In Motor Neuron Cell Lines, Katsiaryna Milashevich

Student Theses

Although non-essential, glycine plays an important role in major metabolic reactions and is most known for its anti-inflammatory effects. An accumulation of contemporary research has shown that glycine is able to stabilize membrane potential using glycine receptors at the cellular level and to protect mitochondrial function directly, whether it is from inflammation, heavy metal poisoning, or ischemia-induced neuroinflammation. In this research, the existence of a hypothetical mitochondrial glycine receptor is examined. Immunofluorescence imaging was used to examine the presence of the glycine receptor subunits alpha 1 and alpha 2 in both non- differentiated and differentiated neuroblastoma cell lines. The preliminary ...


Vitamin B12 Deficiency Does Not Stimulate Amyloid-Beta Toxicity In A Ceanorhabditis Elegans Model Of Alzheimer’S Disease, Opeyemi F. Showemimo 2021 East Tennessee State University

Vitamin B12 Deficiency Does Not Stimulate Amyloid-Beta Toxicity In A Ceanorhabditis Elegans Model Of Alzheimer’S Disease, Opeyemi F. Showemimo

Electronic Theses and Dissertations

Alzheimer’s disease (AD) is symptomized by amyloid-beta plaques in the brain and accounts for more than 65 percent of dementia cases. Vitamin B12 (cobalamin) deficiency can result in similar cognitive impairment and roughly 15% of the elderly are vitamin B12 deficient. Vitamin B12 deficiency results in the accumulation of toxic methylmalonic acid and homocysteine. Hyperhomocysteinemia is a strong risk factor for AD. To test if vitamin B12 deficiency stimulates amyloid-beta toxicity, Caenorhabditis elegans expressing amyloid-beta in muscle were fed either vitamin B12-deficient OP50-1 or vitamin B12-rich HT115(DE3) E. coli bacteria. Increased amyloid-beta toxicity was found in worms fed ...


Psychedelics Can Save: The Scientific And Social Case For Rescheduling Psychedelic Compounds, Galen M. Fader 2021 University of Tennessee, Knoxville

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

Chancellor’s Honors Program Projects

No abstract provided.


Translational Fidelity And Its Role In Neuronal Homeostasis, Markus Terrey 2021 University of Maine

Translational Fidelity And Its Role In Neuronal Homeostasis, Markus Terrey

Electronic Theses and Dissertations

The process of translation, which refers to decoding genetic information from mRNA to protein, is vital for all cellular function. Translational fidelity starts at the level of aminoacylation of transfer RNAs (tRNA). This reaction is catalyzed by aminoacyl tRNA synthetases where each amino acid is transferred to its corresponding cognate tRNA. Because tRNAs harbor the anticodon sequence to decodes a particular mRNA codon, the specific aminoacylation of the tRNA with a cognate amino acid establishes the rules of decoding genetic code into proteins. Aminoacylated tRNAs are then delivered to ribosomes, where ribosomes in a highly organized manner need to accurately ...


Investigating Mechanisms In Nociceptors Driving Ongoing Activity And Ongoing Pain, Elia Lopez 2021 The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences

Investigating Mechanisms In Nociceptors Driving Ongoing Activity And Ongoing Pain, Elia Lopez

The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences Dissertations and Theses (Open Access)

Ongoing (apparently spontaneous) pain at rest is a major complaint of patients suffering from many forms of acute and chronic pain, including acute and persistent postsurgical pain. Accumulating evidence suggests ongoing activity in nociceptors is a major driver of ongoing pain. Ongoing activity can be generated in sensory neurons in the absence of sensory generator potentials if one or more of three neurophysiological alterations occur – prolonged depolarization of resting membrane potential (RMP), hyperpolarization of action potential (AP) threshold, and/or increased amplitude of depolarizing spontaneous fluctuations of membrane potential (DSFs) to bridge the gap between RMP and AP threshold. Cellular ...


Npy Expression Of Low-Birth Weight Offspring In Nutrient-Restricted Utero, Janine Levandowski, Holly Young 2021 Susquehanna University

Npy Expression Of Low-Birth Weight Offspring In Nutrient-Restricted Utero, Janine Levandowski, Holly Young

Senior Scholars Day

No abstract provided.


Validation Of Induced Microglia-Like Cells (Img Cells) For Future Studies Of Brain Diseases, Atoshi Banerjee, Yimei Lu, Kenny Do, Travis Mize, Xiaogang Wu, Xiangning Chen, Jingchun Chen 2021 University of Nevada, Las Vegas

Validation Of Induced Microglia-Like Cells (Img Cells) For Future Studies Of Brain Diseases, Atoshi Banerjee, Yimei Lu, Kenny Do, Travis Mize, Xiaogang Wu, Xiangning Chen, Jingchun Chen

School of Medicine Faculty Publications

Microglia are the primary resident immune cells of the central nervous system that maintain physiological homeostasis in the brain and contribute to the pathogenesis of many psychiatric disorders and neurodegenerative diseases. Due to the lack of appropriate human cellular models, it is difficult to study the basic pathophysiological processes linking microglia to brain diseases. In this study, we adopted a microglia-like cellular model derived from peripheral blood monocytes with granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-34 (IL-34). We characterized and validated this in vitro cellular model by morphology, immunocytochemistry, gene expression profiles, and functional study. Our results indicated that the iMG ...


Anhedonia And Its Intervention In Depressive Adults: New Developments Based On Research Domain Criteria (Rdoc) In Mental Illnesses, J. Mao, J. Yuan 2021 Faculty of Psychology, Southwest University, Chongqing 400715, China

Anhedonia And Its Intervention In Depressive Adults: New Developments Based On Research Domain Criteria (Rdoc) In Mental Illnesses, J. Mao, J. Yuan

Stress and Brain

Anhedonia, as one of the core symptoms of depression, is of great significance for the diagnosis and treatment of depression. Traditionally, anhedonia has been referred to as "loss of pleasure" , while the recent research emphasizes that anhedonia is a complex and multidimensional construct based on reward processing impairment. Exploring different manifestations of anhedonia and developing the corresponding interventions have become indispensable in the current research of depression. Based on the positive valence system of the Research Domain Criteria (RDoC), this paper firstly demonstrates that the anhedonia of depressive adults are mainly characterized by the impairments in anticipatory pleasure, incentive motivation ...


Exposure To Single Prolonged Stress Fails To Induce Anxiety-Like Behavior In Mice, W-J. You, Y. He, W-Z. Liu, Yu-Ge Zhu, Ping Hu, Bing-Xing Pan, Wen-Hua Zhang 2021 Laboratory of Fear and Anxiety Disorders, Institute of Life Science, Nanchang University, Nanchang 330031, China

Exposure To Single Prolonged Stress Fails To Induce Anxiety-Like Behavior In Mice, W-J. You, Y. He, W-Z. Liu, Yu-Ge Zhu, Ping Hu, Bing-Xing Pan, Wen-Hua Zhang

Stress and Brain

Single prolonged stress (SPS) is a well-established and most frequently used rat model to induce post-traumatic stress disorder (PTSD)-like symptoms, which helps to understand the neurobiological mechanisms as well as developing novel therapeutic strategies for PTSD. However, whether such stress model works efficiently in mice remains unknown. In the present study, we established a mouse SPS (mSPS) model by exposing C57BL/6J mice to a series of multimodal stressors on a single day, then the anxiety-like behavior was measured by open-field test, elevated plus maze test, dark-light box, and novelty-suppressed feeding test. Our results showed that mSPS had no ...


A Meta-Analysis Of Brain Dna Methylation Across Sex, Age, And Alzheimer's Disease Points For Accelerated Epigenetic Aging In Neurodegeneration, Camilla Pellegrini, Danielle Fernandes Durso, Maria Giulia Bacalini 2021 Institute of Neurological Sciences of Bologna

A Meta-Analysis Of Brain Dna Methylation Across Sex, Age, And Alzheimer's Disease Points For Accelerated Epigenetic Aging In Neurodegeneration, Camilla Pellegrini, Danielle Fernandes Durso, Maria Giulia Bacalini

Open Access Publications by UMMS Authors

Alzheimer's disease (AD) is characterized by specific alterations of brain DNA methylation (DNAm) patterns. Age and sex, two major risk factors for AD, are also known to largely affect the epigenetic profiles in brain, but their contribution to AD-associated DNAm changes has been poorly investigated. In this study we considered publicly available DNAm datasets of four brain regions (temporal, frontal, entorhinal cortex, and cerebellum) from healthy adult subjects and AD patients, and performed a meta-analysis to identify sex-, age-, and AD-associated epigenetic profiles. In one of these datasets it was also possible to distinguish 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC ...


Quantifying And Mitigating Motor Phenotypes Induced By Antisense Oligonucleotides In The Central Nervous System [Preprint], Michael P. Moazami, Julia M. Rembetsy-Brown, Feng Wang, Pranathi Meda Krishnamurthy, Alexandra Weiss, Miklos G. Marosfoi, Robert M. King, Mona Motwani, Heather L. Gray-Edwards, Katherine A. Fitzgerald, Robert H. Brown Jr., Jonathan K. Watts 2021 University of Massachusetts Medical School

Quantifying And Mitigating Motor Phenotypes Induced By Antisense Oligonucleotides In The Central Nervous System [Preprint], Michael P. Moazami, Julia M. Rembetsy-Brown, Feng Wang, Pranathi Meda Krishnamurthy, Alexandra Weiss, Miklos G. Marosfoi, Robert M. King, Mona Motwani, Heather L. Gray-Edwards, Katherine A. Fitzgerald, Robert H. Brown Jr., Jonathan K. Watts

University of Massachusetts Medical School Faculty Publications

Antisense oligonucleotides (ASOs) are emerging as a promising class of therapeutics for neurological diseases. When injected directly into the cerebrospinal fluid, ASOs distribute broadly across brain regions and exert long-lasting therapeutic effects. However, many phosphorothioate (PS)-modified gapmer ASOs show transient motor phenotypes when injected into the cerebrospinal fluid, ranging from reduced motor activity to ataxia or acute seizure-like phenotypes. The effect of sugar and phosphate modifications on these phenotypes has not previously been systematically studied. Using a behavioral scoring assay customized to reflect the timing and nature of these effects, we show that both sugar and phosphate modifications influence ...


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