A Mouse Model With Widespread Expression Of The C9orf72-Linked Glycine-Arginine Dipeptide Displays Non-Lethal Als/Ftd-Like Phenotypes,
2022
Thomas Jefferson University
A Mouse Model With Widespread Expression Of The C9orf72-Linked Glycine-Arginine Dipeptide Displays Non-Lethal Als/Ftd-Like Phenotypes, Brandie Morris Verdone, Maria Elena Cicardi, Xinmei Wen, Sindhu Sriramoji, Katelyn Russell, Shashirekha S Markandaiah, Brigid K Jensen, Karthik Krishnamurthy, Aaron R. Haeusler, Piera Pasinelli, Davide Trotti
Department of Neuroscience Faculty Papers
Translation of the hexanucleotide G4C2 expansion associated with C9orf72 amyotrophic lateral sclerosis and frontotemporal dementia (ALS/FTD) produces five different dipeptide repeat protein (DPR) species that can confer toxicity. There is yet much to learn about the contribution of a single DPR to disease pathogenesis. We show here that a short repeat length is sufficient for the DPR poly-GR to confer neurotoxicity in vitro, a phenomenon previously unobserved. This toxicity is also reported in vivo in our novel knock-in mouse model characterized by widespread central nervous system (CNS) expression of the short-length poly-GR. We observe sex-specific chronic ALS/FTD-like phenotypes in these …
Sex Differences In Hippocampal O-Glcnacylation Of The Adult Mouse Brain,
2022
Southeastern University - Lakeland
Sex Differences In Hippocampal O-Glcnacylation Of The Adult Mouse Brain, Makenzie Johnson
Selected Honors Theses
The hippocampus is a structure in the brain crucial for learning and memory. This occurs by synaptic remodeling known as long term potentiation and long term depression. Modifications of proteins in the hippocampus can affect its function. One of these modifications is the addition of O-linked β-N-acetylglucosamine, also known as O-GlcNAc. This is a sugar produced from glucose by the hexosamine biosynthetic pathway that is reversibly added onto serine and threonine residues of proteins by O-GlcNAc Transferase, or OGT. It is reversibly removed from these residues by O-GlcNAcAse, or OGA. This modification has been implicated in diabetes, cardiac dysfunction, and …
“The Role Of The Endothelin-1 Pathway In The Disruption Of The Blood Brain Barrier In Neuro-Inflammatory Disease”,
2022
John Carroll University
“The Role Of The Endothelin-1 Pathway In The Disruption Of The Blood Brain Barrier In Neuro-Inflammatory Disease”, Sarah Fallavollita
Celebration of Scholarship 2022
Multiple sclerosis (MS) is an autoimmune neuro-inflammatory disease characterized by disruption of the blood brain barrier (BBB) and demyelination of axons. MS does not occur naturally in mice, so a mouse model of the disease called experimental autoimmune encephalomyelitis (EAE) was used as it produces pathological symptoms like those of MS. In this double-blind experiment, healthy control mice, EAE mice, and EAE mice treated with bosentan (a drug that blocks the endothelin pro-inflammatory pathway) were compared based the amount of fibrinogen that leaked into the parenchyma of the spinal cord. Overall, the experiment resulted in a statistically significant reduction in …
Targeting Notch3 With Crispr-Cas9 Technology In Zebrafish Retinal Degeneration Models,
2022
John Carroll University
Targeting Notch3 With Crispr-Cas9 Technology In Zebrafish Retinal Degeneration Models, Emily Januck
Celebration of Scholarship 2022
Teleost fish such as zebrafish (Danio rerio) have shown the ability to regenerate damaged photoreceptors due to the robust activity of Müller glia [1]. Interestingly, the Müller glia in retinal disease model zebrafish such as bbs2, cep290, and eys do not respond like those in normal zebrafish, making these genotypes a good model to study treatment options in humans [2, 3, 4]. The Notch signaling pathway is a highly conserved cell signaling pathway in many organisms that plays a role in determining cell fates in developmental processes [5]. Specifically, the notch3 gene has been studied and shown to have effects …
An Unfinished Melody: Mental Illness, Worship Music, And The Tension Of The Pentecostal “Now” And “Not Yet,
2022
Southeastern University - Lakeland
An Unfinished Melody: Mental Illness, Worship Music, And The Tension Of The Pentecostal “Now” And “Not Yet, Brianna Turbeville
Masters of Theological Studies
According to the National Institute of Mental Health, it is estimated that nearly 20% of adults within the United States suffer from some form of mental illness.1 With roughly one-fifth, if not more, of the entire U.S. population facing a daily internal battle of some sort, this is an issue that is certainly elemental to the overarching purpose of the Church as an agent of reconciliation of creation with Creator. A prevalent problem requires prevalent solutions. What is something even more pervasive in every culture than mental health? Music. Melodies and lyrics are native to virtually every individual on earth. …
Epigenetic Pathogenesis Of Neurological Disorders In Utero And Considerations For Genetic Counseling,
2022
Liberty University
Epigenetic Pathogenesis Of Neurological Disorders In Utero And Considerations For Genetic Counseling, Lauren Juga
Senior Honors Theses
Epigenetic modifications are a major focus of study in the pathogenesis of many disorders regarding metabolism, aging, neurodevelopment, and neurodegeneration. Epigenetic mechanisms are present throughout life but are especially vital to guiding fetal development. The precise timing of gene activation and deactivation guides stem cell differentiation through each embryonic stage. After exposure to environmental stimuli, gene expression can be altered by transcription factors, resulting in observable phenotypes and even pathology. Here, the epigenetic mechanisms responsible for the pathogenesis of neurodevelopmental and neuropsychiatric disorders are explored in response to environmental perturbations in utero. The present goal is to identify correlations between …
Applications And Challenges Of Neural Stem Cell Therapy,
2022
Liberty University
Applications And Challenges Of Neural Stem Cell Therapy, John Brewster
Senior Honors Theses
In response to the many neurological disorders that plague humanity, no treatment shows more promise than stem cell therapy. By using these special cells to regrow damaged neurons and combat sources of disease in affected patients, researchers hope to treat neurological disorders of all kinds. While great strides have been made in laboratory settings, the widespread use of stem cells to treat neurological disorders in humans is still a distant goal. Recent advancements have been made in the area of neural stem cell therapy, but complications arise when using this method to treat neurological disorders.
Determining The Genomic Localization And Binding Partners Of Zinc Finger Protein 410,
2022
Liberty University
Determining The Genomic Localization And Binding Partners Of Zinc Finger Protein 410, Mariko Locke
Senior Honors Theses
The results of a folate deficiency study affecting cognition in mice suggested the altered genes may be controlled by a transcription factor known as Zinc Finger Protein 410 (Zfp410). Due to a lack of literature on Zfp410’s interacting proteins and DNA-binding location, our study aims to further elucidate the role Zfp410 plays in affecting cognition. A custom antibody was used to determine the Zfp410 isoforms present in mouse and rat brains. Moreover, the antibody was used to determine the binding partners of Zfp410 in the brain and locate specific genomic regions/sequences with which it associates in vivo. These results may …
Neuroscience Directed Study/Special Topics Neu 391,
2022
University of Rhode Island
Neuroscience Directed Study/Special Topics Neu 391, Joanna Burkhardt
Library Impact Statements
No abstract provided.
Small Heat Shock Protein 22 Preserves Neuronal Function In A Murine Model Of Tauopathy,
2022
University of South Florida
Small Heat Shock Protein 22 Preserves Neuronal Function In A Murine Model Of Tauopathy, Santiago Rodriguez Ospina
USF Tampa Graduate Theses and Dissertations
Proteinopathies is a family of diseases associated with the pathological aggregation of protein. There are a multitude of proteinopathies, like tauopathy and synucleinopathy that contribute to neurodegenerative diseases like Alzheimer’s disease (AD), Creutzfeldt-Jakob, Pick’s disease, Frontotemporal dementia, and Parkinson’s disease (PD). Currently, one focus of research in the field is mitigating aggregation-prone proteins contributing to disease state. One method of targeting aggregation is the use of chaperones. Chaperones are molecular machinery that help maintain homeostasis in the cells, through various roles and mechanisms, one of those methods is to regulate protein aggregation. Chaperones can achieve this by affecting protein-protein interactions, …
Mutant Lrrk2 In Lymphocytes Regulates Neurodegeneration Via Il-6 In An Inflammatory Model Of Parkinson's Disease,
2022
Thomas Jefferson University
Mutant Lrrk2 In Lymphocytes Regulates Neurodegeneration Via Il-6 In An Inflammatory Model Of Parkinson's Disease, Elena Kozina, Matthew D. Byrne, Richard Jay Smeyne
Department of Neuroscience Faculty Papers
Mutations in a number of genes contribute to development of Parkinson's disease (PD), including several within the LRRK2 gene. However, little is known about the signals that underlie LRRK2-mediated neuronal loss. One clue resides in the finding that the neurodegenerative cascades emanate from signals arising from the peripheral immune system. Here, using two chimeric mouse models, we demonstrate that: 1) the replacement of mutant LRRK2 with wt form of the protein in T- and B-lymphocytes diminishes LPS-mediated inflammation and rescues the SNpc DA neuron loss in the mutant LRRK2 brain; 2) the presence of G2019S or R1441G LRRK2 mutation in …
Astrocyte-Secreted Chordin-Like 1 Regulates Spine Density After Ischemic Injury,
2022
Thomas Jefferson University
Astrocyte-Secreted Chordin-Like 1 Regulates Spine Density After Ischemic Injury, Elena Blanco-Suarez, Nicola J Allen
Department of Neuroscience Faculty Papers
Ischemic injury occurs when the brain is deprived of blood flow, preventing cells from receiving essential nutrients. The injury core is the brain region directly deprived and is surrounded by the peri-infarct area, the region with recovery potential. In the peri-infarct area neurons undergo acute loss of dendritic spines, which modifies synaptic plasticity and determines neuronal survival. Astrocytes can be protective or detrimental to the ischemic injury response depending on the specific stage, yet we lack clear understanding of the underlying mechanisms. Chordin-like 1 (Chrdl1) is an astrocyte-secreted protein that promotes synaptic maturation and limits experience-dependent plasticity in the mouse …
Rotenone Induces Regionally Distinct Α-Synuclein Protein Aggregation And Activation Of Glia Prior To Loss Of Dopaminergic Neurons In C57bl/6 Mice,
2022
Colorado State University
Rotenone Induces Regionally Distinct Α-Synuclein Protein Aggregation And Activation Of Glia Prior To Loss Of Dopaminergic Neurons In C57bl/6 Mice, Savannah M Rocha, Collin M Bantle, Tawfik Aboellail, Debotri Chatterjee, Richard Jay Smeyne, Ronald B Tjalkens
Department of Neuroscience Faculty Papers
Rotenone is a naturally occurring insecticide that inhibits mitochondrial complex I and leads to neurochemical and neuropathological deficits closely resembling those in Parkinson's disease (PD). Deficits include loss of dopaminergic neurons (DAn) in the substantia nigra pars compacta (SNpc), decreased dopamine levels and aggregation of misfolded alpha-synuclein (p129). In rat models of rotenone-induced parkinsonism, the progression of neuronal injury has been associated with activation of microglia and astrocytes. However, these neuroinflammatory changes have been challenging to study in mice, in part because the systemic rotenone exposure model utilized in rats is more toxic to mice. To establish a reproducible murine …
Evaluation Of Hippocampal Allostatic Load-Associated Factors In Animal Models Of Post-Traumatic Stress Disorder: Relevance To Human Ptsd,
2022
Louisiana State University
Evaluation Of Hippocampal Allostatic Load-Associated Factors In Animal Models Of Post-Traumatic Stress Disorder: Relevance To Human Ptsd, Dennis Parker Kelley
LSU Doctoral Dissertations
Post-traumatic stress disorder (PTSD) is associated with elevated allostatic load, nearly double the risk for metabolic syndrome, reduced hippocampal volume, and contextual memory processing deficits. Emerging evidence suggests that these stress effects may predispose individuals to the development of PTSD, and there is a known relationship between chronic stress and metabolic dysfunction. In this work, we utilized two rat models of PTSD to explore these connections. We used an acute predator odor stressor to investigate the relationship between PTSD-like behaviors and mitochondrial dysfunction in the hippocampus of rats, and we observed that conditioned place avoidance was associated with reduced mitochondrial …
Pituitary Adenylate Cyclase-Activating Polypeptide Receptor Activation In The Hypothalamus Recruits Unique Signaling Pathways Involved In Energy Homeostasis,
2022
Marquette University
Pituitary Adenylate Cyclase-Activating Polypeptide Receptor Activation In The Hypothalamus Recruits Unique Signaling Pathways Involved In Energy Homeostasis, Brian Maunze, Katherine Wood Bruckner, Nikhil Nilesh Desai, Christopher Chen, Fanghong Chen, David Baker, Sujean Choi
Biomedical Sciences Faculty Research and Publications
Pituitary adenylate cyclase activating polypeptide (PACAP) exerts pleiotropic effects on ventromedial nuclei (VMN) of the hypothalamus and its control of feeding and energy expenditure through the type I PAC1 receptor (PAC1R). However, the endogenous role of PAC1Rs in the VMN and the downstream signaling responsible for PACAP’s effects on energy balance are unknown. Numerous studies have revealed that PAC1Rs are coupled to both Gαs/adenylyl cyclase/protein kinase A (Gαs/AC/PKA) and Gαq/phospholipase C/protein kinase C (Gαq/PLC/PKC), while also undergoing trafficking following stimulation. To determine the endogenous role of PAC1Rs and downstream signaling that may explain PACAP’s pleiotropic effects, we used RNA interference …
Addressing The Disparities In Dementia Risk, Early Detection And Care In Latino Populations: Highlights From The Second Latinos & Alzheimer's Symposium,
2022
The University of Texas Rio Grande Valley
Addressing The Disparities In Dementia Risk, Early Detection And Care In Latino Populations: Highlights From The Second Latinos & Alzheimer's Symposium, Yakeel T. Quiroz, Michele Solis, María P. Aranda, Alicia I. Arbaje, Mirna Arroyo-Miranda, Laura Y. Cabrera, Minerva Maria Carrasquillo, Maria M. Corrada, Gladys E. Maestre, Rosa V. Pirela
School of Medicine Publications and Presentations
The Alzheimer's Association hosted the second Latinos & Alzheimer's Symposium in May 2021. Due to the COVID-19 pandemic, the meeting was held online over 2 days, with virtual presentations, discussions, mentoring sessions, and posters. The Latino population in the United States is projected to have the steepest increase in Alzheimer's disease (AD) in the next 40 years, compared to other ethnic groups. Latinos have increased risk for AD and other dementias, limited access to quality care, and are severely underrepresented in AD and dementia research and clinical trials. The symposium highlighted developments in AD research with Latino populations, including advances …
Response Of Astrocyte Subpopulations Following Spinal Cord Injury.,
2022
Department of Neuroscience, Vickie and Jack Farber Institute for Neuroscience, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA 19107, USA
Response Of Astrocyte Subpopulations Following Spinal Cord Injury., R Vivian Allahyari, Nicolette M Heinsinger, Daniel Hwang, David A Jaffe, Javad Rasouli, Stephanie Shiers, Samantha J Thomas, Theodore J Price, Abdolmohamad Rostami, Angelo C Lepore
Farber Institute for Neuroscience Faculty Papers
There is growing appreciation for astrocyte heterogeneity both across and within central nervous system (CNS) regions, as well as between intact and diseased states. Recent work identified multiple astrocyte subpopulations in mature brain. Interestingly, one subpopulation (Population C) was shown to possess significantly enhanced synaptogenic properties in vitro, as compared with other astrocyte subpopulations of adult cortex and spinal cord. Following spinal cord injury (SCI), damaged neurons lose synaptic connections with neuronal partners, resulting in persistent functional loss. We determined whether SCI induces an enhanced synaptomodulatory astrocyte phenotype by shifting toward a greater proportion of Population C cells and/or increasing …
Blood-Brain Barrier Disruption Mediated By Ffa1 Receptor-Evidence Using Miniscope,
2022
Thomas Jefferson University
Blood-Brain Barrier Disruption Mediated By Ffa1 Receptor-Evidence Using Miniscope, Kristen L Lindenau, Jeffrey L Barr, Christopher R Higgins, Kevin T Sporici, Eugen Brailoiu, G Cristina Brailoiu
College of Pharmacy Faculty Papers
Omega-3 polyunsaturated fatty acids (n-3 PUFAs), obtained from diet and dietary supplements, have been tested in clinical trials for the prevention or treatment of several diseases. n-3 PUFAs exert their effects by activation of free fatty acid (FFA) receptors. FFA1 receptor, expressed in the pancreas and brain, is activated by medium- to long-chain fatty acids. Despite some beneficial effects on cognition, the effects of n-3 PUFAs on the blood-brain barrier (BBB) are not clearly understood. We examined the effects of FFA1 activation on BBB permeability in vitro, using rat brain microvascular endothelial cells (RBMVEC), and in vivo, by assessing Evans …
Response Of Astrocyte Subpopulations Following Spinal Cord Injury,
2022
Thomas Jefferson University
Response Of Astrocyte Subpopulations Following Spinal Cord Injury, R Vivian Allahyari, Nicolette M Heinsinger, Daniel Hwang, David A Jaffe, Javad Rasouli, Stephanie Shiers, Samantha J Thomas, Theodore J Price, A M Rostami, Angelo C Lepore
Department of Neuroscience Faculty Papers
There is growing appreciation for astrocyte heterogeneity both across and within central nervous system (CNS) regions, as well as between intact and diseased states. Recent work identified multiple astrocyte subpopulations in mature brain. Interestingly, one subpopulation (Population C) was shown to possess significantly enhanced synaptogenic properties in vitro, as compared with other astrocyte subpopulations of adult cortex and spinal cord. Following spinal cord injury (SCI), damaged neurons lose synaptic connections with neuronal partners, resulting in persistent functional loss. We determined whether SCI induces an enhanced synaptomodulatory astrocyte phenotype by shifting toward a greater proportion of Population C cells and/or increasing …
Seizure Prediction In Epilepsy Patients,
2022
Nova Southeastern University
Seizure Prediction In Epilepsy Patients, Gary Dean Cravens
NSU REACH and IPE Day
Purpose/Objective: Characterize rigorously the preictal period in epilepsy patients to improve the development of seizure prediction techniques. Background/Rationale: 30% of epilepsy patients are not well-controlled on medications and would benefit immensely from reliable seizure prediction. Methods/Methodology: Computational model consisting of in-silico Hodgkin-Huxley neurons arranged in a small-world topology using the Watts-Strogatz algorithm is used to generate synthetic electrocorticographic (ECoG) signals. ECoG data from 18 epilepsy patients is used to validate the model. Unsupervised machine learning is used with both patient and synthetic data to identify potential electrophysiologic biomarkers of the preictal period. Results/Findings: The model has shown states corresponding to …
