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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 ...


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 ...


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.


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 ...


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 ...


Third Harmonic Generation: A Method For Visualizing Myelin In The Murine Cerebral Cortex, Michael Redlich 2021 The Graduate Center, City University of New York

Third Harmonic Generation: A Method For Visualizing Myelin In The Murine Cerebral Cortex, Michael Redlich

Dissertations, Theses, and Capstone Projects

Here we present the use of Third Harmonic Generation (THG) for the label-free imaging of myelinated axons in the murine cerebral cortex. Myelin plays an important role in the processes of learning and disease. However, much of the myelin biology research thus far has focused on white matter tracts where myelin is more visible. Much is still unknown, particularly with regard to myelin in gray matter. First, we engage in THG microscopy using an optical parametric oscillator pumped by a titanium-sapphire laser to demonstrate the utility of the technique for imaging myelin in vivo. Second, we investigate the use of ...


Glial Cell Dysfunction In C9orf72-Related Amyotrophic Lateral Sclerosis And Frontotemporal Dementia, Mehdi Ghasemi, Kiandokht Keyhanian, Catherine Douthwright 2021 University of Massachusetts Medical School

Glial Cell Dysfunction In C9orf72-Related Amyotrophic Lateral Sclerosis And Frontotemporal Dementia, Mehdi Ghasemi, Kiandokht Keyhanian, Catherine Douthwright

Open Access Publications by UMMS Authors

Since the discovery of the chromosome 9 open reading frame 72 (C9orf72) repeat expansion mutation in 2011 as the most common genetic abnormality in amyotrophic lateral sclerosis (ALS, also known as Lou Gehrig's disease) and frontotemporal dementia (FTD), progress in understanding the signaling pathways related to this mutation can only be described as intriguing. Two major theories have been suggested-(i) loss of function or haploinsufficiency and (ii) toxic gain of function from either C9orf72 repeat RNA or dipeptide repeat proteins (DPRs) generated from repeat-associated non-ATG (RAN) translation. Each theory has provided various signaling pathways that potentially participate in ...


Behavioral Arrest And A Characteristic Slow Waveform Are Hallmark Responses To Selective 5-Ht2a Receptor Activation, April Contreras, Matthew Khumnark, Rochelle M. Hines, Dustin J. Hines 2021 University of Nevada, Las Vegas

Behavioral Arrest And A Characteristic Slow Waveform Are Hallmark Responses To Selective 5-Ht2a Receptor Activation, April Contreras, Matthew Khumnark, Rochelle M. Hines, Dustin J. Hines

Psychology Faculty Publications

© 2021, The Author(s). Perception, emotion, and mood are powerfully modulated by serotonin receptor (5-HTR) agonists including hallucinogens. The 5-HT2AR subtype has been shown to be central to hallucinogen action, yet the precise mechanisms mediating the response to 5-HT2AR activation remain unclear. Hallucinogens induce the head twitch response (HTR) in rodents, which is the most commonly used behavioral readout of hallucinogen pharmacology. While the HTR provides a key behavioral signature, less is known about the meso level changes that are induced by 5-HT2AR activation. In response to administration of the potent and highly selective 5-HT2AR agonist 25I-NBOH in mice, we ...


Deletions In Cwh43 Cause Idiopathic Normal Pressure Hydrocephalus, Hong Wei Yang, Dejun Yang, Huijun Dai, Yan Zhang, Sijun Zhao, Shuo Zhang, Yan Ma, George Wang, Shaokuan Zheng, Rona S. Carroll, Mark D. Johnson 2021 University of Massachusetts Medical School

Deletions In Cwh43 Cause Idiopathic Normal Pressure Hydrocephalus, Hong Wei Yang, Dejun Yang, Huijun Dai, Yan Zhang, Sijun Zhao, Shuo Zhang, Yan Ma, George Wang, Shaokuan Zheng, Rona S. Carroll, Mark D. Johnson

Radiology Publications

Idiopathic normal pressure hydrocephalus (iNPH) is a neurological disorder that occurs in about 1% of individuals over age 60 and is characterized by enlarged cerebral ventricles, gait difficulty, incontinence, and cognitive decline. The cause and pathophysiology of iNPH are largely unknown. We performed whole exome sequencing of DNA obtained from 53 unrelated iNPH patients. Two recurrent heterozygous loss of function deletions in CWH43 were observed in 15% of iNPH patients and were significantly enriched 6.6-fold and 2.7-fold, respectively, when compared to the general population. Cwh43 modifies the lipid anchor of glycosylphosphatidylinositol-anchored proteins. Mice heterozygous for CWH43 deletion appeared ...


Genetic Analysis Of Amyotrophic Lateral Sclerosis Identifies Contributing Pathways And Cell Types, Sara Saez-Atienzar, John E. Landers 2021 National Institutes of Health

Genetic Analysis Of Amyotrophic Lateral Sclerosis Identifies Contributing Pathways And Cell Types, Sara Saez-Atienzar, John E. Landers

Open Access Publications by UMMS Authors

Despite the considerable progress in unraveling the genetic causes of amyotrophic lateral sclerosis (ALS), we do not fully understand the molecular mechanisms underlying the disease. We analyzed genome-wide data involving 78,500 individuals using a polygenic risk score approach to identify the biological pathways and cell types involved in ALS. This data-driven approach identified multiple aspects of the biology underlying the disease that resolved into broader themes, namely, neuron projection morphogenesis, membrane trafficking, and signal transduction mediated by ribonucleotides. We also found that genomic risk in ALS maps consistently to GABAergic interneurons and oligodendrocytes, as confirmed in human single-nucleus RNA-seq ...


Mitochondrial Aspects Of Neuronal Pathology In Triple-Transgenic Alzheimer’S Disease Mice, John Zachary Cavendish 2021 West Virginia University

Mitochondrial Aspects Of Neuronal Pathology In Triple-Transgenic Alzheimer’S Disease Mice, John Zachary Cavendish

Graduate Theses, Dissertations, and Problem Reports

Alzheimer’s disease (AD) is a fatal, progressive neurodegenerative disease afflicting millions of people in the United States alone and is the only one of the top leading causes of morbidity and mortality with no effective disease-modifying therapies. It is the most common form of dementia, affecting one in three people over the age of 85. While the hallmarks of the disease include accumulation of beta-amyloid-based extracellular plaques and hyperphosphorylated tau-based intracellular neurofibrillary tangles, treatment strategies centered on removing or mitigating these components of AD have all failed in humans. Mitochondrial dysfunction has been increasingly recognized as an early and ...


Genus Applications For Alzheimer's Disease Pathology, Whitney L Carter 2021 University of Louisville

Genus Applications For Alzheimer's Disease Pathology, Whitney L Carter

Undergraduate Arts and Research Showcase

Estimates vary, but it is thought that 5.5 million Americans age 60 and up may be living with Alzheimer’s diseases (AD). AD is the most common type of dementia and is characterized by a decline in episodic memories, long-term memory, language, attention, and personality changes. The first symptoms can vary, but for most people memory is the first capacity to become impaired. However, symptoms can also be a decline in non-memory aspects of cognition like work-finding, vision/spatial issues, and impaired reasoning or judgement. AD is identified mainly by two histopathological features: extracellular plague of amyloid-beta protein and ...


The Effects Of Rolipram, A Selective Phosphodiesterase Inhibitor, On Immortalized Schwann Cell Proliferation, Akap95 And Cyclin D3 Expression, Kyle P. Kenney, Mary Pistack, Angela Asirvatham 2021 Misericordia University

The Effects Of Rolipram, A Selective Phosphodiesterase Inhibitor, On Immortalized Schwann Cell Proliferation, Akap95 And Cyclin D3 Expression, Kyle P. Kenney, Mary Pistack, Angela Asirvatham

Student Research Poster Presentations 2021

Schwann cells are a vital component of the Peripheral Nervous System and aid in the repair of axons following injury. The regulation of Schwann cell growth in vitro is facilitated by heregulin, a neuron-secreted growth factor, and an unknown mitogen that activates the cyclic adenosine monophosphate (cAMP) pathway. The abundance of intracellular cAMP is regulated by a family of enzymes called phosphodiesterases (PDEs). PDE inhibitors such as rolipram have therapeutic potential in various disorders and function by increasing the levels of intracellular cAMP. A-Kinase anchoring proteins (AKAPs), a family of scaffolding proteins that belong to the cAMP/Protein Kinase A ...


Opioid Use Disorder: The Timeline For Medication Assisted Therapy, Alexander Cristofori 2021 Arcadia University

Opioid Use Disorder: The Timeline For Medication Assisted Therapy, Alexander Cristofori

Capstone Showcase

Opioid Use Disorder is patterns of opioid use leading to withdrawal, giving up important life events in order to use opioids, and excessive time spent using opioids, to name a few diagnostic criteria. The clinical progression of the disorder involves periods of acute exacerbation and remission that are cyclic in nature. Treatment is most effective when it includes both pharmacological and psychosocial modalities, referred to as medication assisted therapy (MAT). Three drugs used commonly in MAT-based treatment for OUD from oldest to newest include Methadone, Buprenorphine-naloxone, and Naltrexone. Treatment program models that prioritize total abstinence from the addictive substance attached ...


Preventing Neurodegeneration By Controlling Oxidative Stress: The Role Of Oxr1, Michael R. Volkert, David J. Crowley 2020 University of Massachusetts Medical School

Preventing Neurodegeneration By Controlling Oxidative Stress: The Role Of Oxr1, Michael R. Volkert, David J. Crowley

Open Access Publications by UMMS Authors

Parkinson's disease, diabetic retinopathy, hyperoxia induced retinopathy, and neuronal damage resulting from ischemia are among the notable neurodegenerative diseases in which oxidative stress occurs shortly before the onset of neurodegeneration. A shared feature of these diseases is the depletion of OXR1 (oxidation resistance 1) gene products shortly before the onset of neurodegeneration. In animal models of these diseases, restoration of OXR1 has been shown to reduce or eliminate the deleterious effects of oxidative stress induced cell death, delay the onset of symptoms, and reduce overall severity. Moreover, increasing OXR1 expression in cells further increases oxidative stress resistance and delays ...


Sexually Dimorphic Oxytocin Receptor-Expressing Neurons In The Anteroventral Periventricular Nucleus Regulates Maternal Behavior, Kaustubh Sharma 2020 Louisiana State University and Agricultural and Mechanical College

Sexually Dimorphic Oxytocin Receptor-Expressing Neurons In The Anteroventral Periventricular Nucleus Regulates Maternal Behavior, Kaustubh Sharma

LSU Doctoral Dissertations

The neurohypophysial hormone oxytocin is involved in the regulation of social behaviors, including social recognition, pair bonding, and sex-specific parental behaviors in a variety of species. Oxytocin triggers these social behaviors by binding to oxytocin receptors (OXTR) in various parts of the brain. Oxytocin-induced sex-typical behavior, therefore, suggests a sexual dimorphic distribution of OXTR in the brain. In recent years, the oxytocin system in the brain received tremendous attention as a potential pharmacological target for treatment of many psychiatric disorders, such as anxiety, autism spectrum disorders, and even sex-specific psychiatric disorder like postpartum depression (PPD). An important problem and a ...


Elucidating The Consequence And Cause Of Microrna Dysregulation In Amyotrophic Lateral Sclerosis (Als), Zachary C. E. Hawley 2020 The University of Western Ontario

Elucidating The Consequence And Cause Of Microrna Dysregulation In Amyotrophic Lateral Sclerosis (Als), Zachary C. E. Hawley

Electronic Thesis and Dissertation Repository

Amyotrophic Lateral Sclerosis (ALS) is a progressive motor neurodegenerative disorder with an average life expectancy of 2-5 years post-diagnosis. Common pathological features associated with ALS are the formation of cytoplasmic inclusions of intermediate filaments and RNA-binding proteins within motor neurons. The formation of intermediate filament cytoplasmic inclusions is believed to be driven by a loss of stochiometric expression between five neuronal intermediate filament proteins—NFL, NFM, NFH, INA and PRPH—where there is a selective suppression of the steady-state levels of NEFL, INA and PRPH mRNA. Further, three RNA-binding proteins—TDP-43, FUS and RGNEF—have been shown to co-aggregate with ...


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