Medical Neurobiology Commons^™

Repetitive Mild Traumatic Brain Injury Impairs Performance In A Rodent Assay Of Cognitive Flexibility, Christopher P. Knapp, Doug P. Fox, Ramesh Raghupathi, Laura L. Giacometti, Stan B. Floresco, Barry D. Waterhouse, Rachel L. Navarra

Rowan-Virtua Research Day

Mild traumatic brain injury (mTBI) occurs in almost 80% of the 3 million reported cases of TBI-related emergency department visits each year in the United States. The majority of mTBIs, sometimes classified as concussions, are due to sports-related activities and typically occur repeatedly over the course of an athlete’s career. mTBI symptoms are generally classified as either somatic or neuropsychiatric/cognitive in nature and include impairments in prefrontal cortex mediated functions, including attention, memory, processing speed, reaction times, problem solving, and cognitive flexibility. To date, there remains a major gap in our understanding of the behavioral manifestations, underlying neurobiology, and treatment …

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 …

Seeing Eye To Eye: A Machine Learning Approach To Automated Saccade Analysis, Maigh Attre

Honors Scholar Theses

Abnormal ocular motility is a common manifestation of many underlying pathologies particularly those that are neurological. Dynamics of saccades, when the eye rapidly changes its point of fixation, have been characterized for many neurological disorders including concussions, traumatic brain injuries (TBI), and Parkinson’s disease. However, widespread saccade analysis for diagnostic and research purposes requires the recognition of certain eye movement parameters. Key information such as velocity and duration must be determined from data based on a wide set of patients’ characteristics that may range in eye shapes and iris, hair and skin pigmentation [36]. Previous work on saccade analysis has …

Changes In Hippocampal-Anterior Cingulate Cortex Interactions During Remote Memory Recall, Ryan A. Wirt

UNLV Theses, Dissertations, Professional Papers, and Capstones

Spatial memory is an important cognitive process that relies on extensive neural networks throughout the brain. The hippocampus (HC) is important for the formation of these memories but over time, in a process referred to as consolidation, recall becomes increasingly reliant on other brain areas. The anterior cingulate cortex (ACC), a region within the medial prefrontal cortex, is important for spatial learning, spatial working memory, and remote memory recall, but the mechanisms underlying recall processes are still unknown. To better understand the role of the ACC and HC during memory recall, we introduced rodents into a series of spatially and …

Does It Matter Whether You Or Your Brain Did It? An Empirical Investigation Of The Influence Of The Double Subject Fallacy On Moral Responsibility Judgments, Uri Maoz, Kellienne R. Sita, Jeroen J. A. Van Boxtel, Liad Mudrik

Psychology Faculty Articles and Research

Despite progress in cognitive neuroscience, we are still far from understanding the relations between the brain and the conscious self. We previously suggested that some neuroscientific texts that attempt to clarify these relations may in fact make them more difficult to understand. Such texts—ranging from popular science to high-impact scientific publications—position the brain and the conscious self as two independent, interacting subjects, capable of possessing opposite psychological states. We termed such writing ‘Double Subject Fallacy’ (DSF). We further suggested that such DSF language, besides being conceptually confusing and reflecting dualistic intuitions, might affect people’s conceptions of moral responsibility, lessening the …

Probiotic Administration As An Adjuvant Therapeutic Treatment For Anxiety, Depression, And Cognitive Impairment Among Hypothyroid Patients, Erin R. Gorman

Selected Honors Theses

Hypothyroidism is a form of thyroid dysfunction that occurs when the thyroid gland does not make and secrete enough thyroid hormones to regulate certain processes in the body. Because thyroid hormones take part in many bodily functions, hypothyroidism can cause a large range of symptoms. Current research indicates that some strains of probiotics have beneficial effects on certain neurological and inflammatory diseases, leading to the impression that they can be used therapeutically for effective treatment of different mental health issues such as anxiety, stress, depression, and impaired memory. Because hypothyroidism often leads to such mental symptoms, it may be possible …

Prefrontal Corticotropin-Releasing Factor (Crf) Neurons Act Locally To Modulate Frontostriatal Cognition And Circuit Function., Sofiya Hupalo, Andrea J Martin, Rebecca K Green, David M Devilbiss, Craig W Berridge

Rowan-Virtua School of Osteopathic Medicine Departmental Research

The PFC and extended frontostriatal circuitry support higher cognitive processes that guide goal-directed behavior. PFC-dependent cognitive dysfunction is a core feature of multiple psychiatric disorders. Unfortunately, a major limiting factor in the development of treatments for PFC cognitive dysfunction is our limited understanding of the neural mechanisms underlying PFC-dependent cognition. We recently demonstrated that activation of corticotropin-releasing factor (CRF) receptors in the caudal dorsomedial PFC (dmPFC) impairs higher cognitive function, as measured in a working memory task. Currently, there remains much unknown about CRF-dependent regulation of cognition, including the source of CRF for cognition-modulating receptors and the output pathways modulated …

The Extreme Effects Of ‘Not-So-Minor’ Concussions: Chronic Traumatic Encephalopathy Literature Review, Alyssa Pierson

Honors Program: Senior Projects (Public)

Many of the concerns that people have with chronic traumatic encephalopathy (CTE) have already been researched for almost a century, but recently, there has been a big push in CTE research. Previous research was done on boxing and football and has now expanded to other contact sports and the military. Risk factors for CTE include repetitive head trauma, the Apoe4 allele, and age of first exposure to brain trauma. A wide range of symptoms may present with CTE, from motor impairment to suicidal ideation. It is believed that a biopsychosocial model should be used when approaching the symptoms of CTE …

Systematic Literature Review Of Quetiapine For The Treatment Of Psychosis In Patients With Parkinsonism, Jack J. Chen, Henry Hua, Lilian Massihi, Ivan Portillo, Azita Alipour, William Ondo, Khashayar Dashtipour

Library Articles and Research

Objective:

The purpose of this article was to determine the efficacy and tolerability of quetiapine compared with placebo or other interventions for psychosis in parkinsonism.

Methods:

Participants with a diagnosis of parkinsonism participated in randomized controlled trials (RCTs) investigating the efficacy and tolerability of quetiapine for psychotic symptoms within a defined follow-up period. The authors conducted searches on PubMed, Cochrane Controlled Register of Trials, and EMBASE for articles published from January 1991 to October 2017. Study methodology and patient- and treatment-level data were independently extracted and summarized by using descriptive statistics. Studies underwent quality assessment for risk of bias.

Results: …

Initial Characterization Of The Indole-3-Carboxamide Bic-154 As A Fast Onset And Reversible Orai Channel Blocker, Tetyana Zhelay, Kalina Szteyn, Elisa Liardo, Jae Eun Cheong, Steffi Koerner, Anil Ekkati, Lijun Sun, J. Ashot Kozak

Neuroscience, Cell Biology & Physiology Faculty Publications

Calcium ion elevations are required for human T-lymphocyte proliferation in response to antigen recognition by a T-cell receptor. Calcium influx through the plasma membrane is necessary for efficient T-cell proliferation and effector function. The calcium channels responsible for Ca2+ influx in lymphocytes have been identified and Orai interacting with ER Ca2+ sensor STIM were shown to be crucial for persistent calcium mobilization. Loss-of-function mutations in Orai1 or STIM1 result in severe combined immunodeficiency (SCID) with muscle hypotonia. Suppression of calcium influx through Orai/STIM channels gives rise to various lymphoproliferative defects. Thus, deletion of Orai or STIM in mice results in …

The Influence Of Unpredictable, Fragmented Parental Signals On The Developing Brain, Laura M. Glynn, Tallie Z. Baram

Psychology Faculty Articles and Research

Mental illnesses originate early in life, governed by environmental and genetic factors. Because parents are a dominant source of signals to the developing child, parental signals - beginning with maternal signals in utero - are primary contributors to children’s mental health. Existing literature on maternal signals has focused almost exclusively on their quality and valence (e.g. maternal depression, sensitivity). Here we identify a novel dimension of maternal signals: their patterns and especially their predictability/unpredictability, as an important determinant of children’s neurodevelopment. We find that unpredictable maternal mood and behavior presage risk for child and adolescent psychopathology. In experimental models, fragmented/unpredictable …

The Promises And Challenges Of Erythropoietin For Treatment Of Alzheimer's Disease, Jiahong Sun, Jan Michelle Martin, Victoria Vanderpoel, Rachita K. Sumbria

Pharmacy Faculty Articles and Research

Alzheimer’s disease (AD) is the most prevalent neurodegenerative disorder in the world, and intracellular neurofibrillary tangles and extracellular amyloid-beta protein deposits represent the major pathological hallmarks of the disease. Currently available treatments provide some symptomatic relief but fail to modify primary pathological processes that underlie the disease. Erythropoietin (EPO), a hematopoietic growth factor, acts primarily to stimulate erythroid cell production, and is clinically used to treat anemia. EPO has evolved as a therapeutic agent for neurodegeneration and has improved neurological outcomes and AD pathology in rodents. However, penetration of the blood–brain barrier (BBB) and negative hematopoietic effects are the two …

Can Nanotechnology Be The Leading Method In Detecting And Treating Cerebral Tumors?, Daniel D. Singh, Zuri Jules-Culver

OUR Journal: ODU Undergraduate Research Journal

Nanotechnology refers to the manipulation or design of materials and structures with desired features in the 1nm–1000 nm size range. The blood brain barrier (BBB) is a major obstacle that drugs must overcome in order to reach tumor cells. The role of this barrier is to transport essential nutrients while protecting and regulating the internal environment. Nanoparticles have been shown to transport drugs through this barrier and accumulate in tumor cells. This is significant since nanoparticles are drug carriers allowing chemotherapeutic drugs to accumulate in target areas (Sun et al., 2017). This is possible because they are able to be …

Axon Initial Segment Integrity In Aging And Traumatic Brain Injury, Mazen M. Gouda

Theses and Dissertations

According to the Center for Disease Control’s (CDC) report to the Congress, there are 2.2 million emergency department visits; 80,000 hospitalizations; and 50,000 deaths each year due to traumatic brain injury. Adults 65 years and older account substantially for the majority of the hospitalization and deaths. Over 70% of the traumatic brain injuries of the older adults are classified as mild to moderate; however, even with these milder injuries, older adults present with a significantly higher morbidity and mortality compared to all other age groups (LeBlanc et al., 2006). With that in mind, it seems essential to develop a deeper …

Autologous Peripheral Nerve Grafts To The Brain For The Treatment Of Parkinson's Disease, Andrew Welleford

Theses and Dissertations--Neuroscience

Parkinson’s disease (PD) is a disorder of the nervous system that causes problems with movement (motor symptoms) as well as other problems such as mood disorders, cognitive changes, sleep disorders, constipation, pain, and other non-motor symptoms. The severity of PD symptoms worsens over time as the disease progresses, and while there are treatments for the motor and some non-motor symptoms there is no known cure for PD. Thus there is a high demand for therapies to slow the progressive neurodegeneration observed in PD. Two clinical trials at the University of Kentucky College of Medicine (NCT02369003, NCT01833364) are currently underway that …

Neurochemical Factors Associated With The Initial Pathophysiological Reaction To Large Vessel Occlusion Stroke, Sarah R. Martha

Theses and Dissertations--Nursing

Ischemic stroke is the leading cause of disability world-wide and affects over 800,000 people per year in the United States. The majority of these strokes are ischemic due to a blockage of blood flow to the brain. Damage to the brain occurs at the onset of stroke, neuronal cell death is irreversible and therefore, quick treatment to remove blockage is critical factor in the recovery from stroke. Mechanical thrombectomy as a treatment for ischemic stroke provides an ideal opportunity to collect blood distal and proximal to the cerebral thrombus to examine neurochemical changes occurring during stroke.

The purpose of this …

Perspectives On Ethnic And Racial Disparities In Alzheimer's Disease And Related Dementias: Update And Areas Of Immediate Need, Ganesh M. Babulal, Yakeel T. Quiroz, Benedict C. Albensi, Eider Arenaza-Urquijo, Arlene J. Astell, Claudio Babiloni, Alex Bahar-Fuchs, Joanne Bell, Gene L. Bowman, Adam M. Brickman, Gael Chetelat, Carrie Ciro, Ann D. Cohen, Peggye Dilworth-Anderson, Hiroko H. Dodge, Simone Dreux, Steven Edland, Anna Esbensen, Lisbeth Evered, Michael Ewers, Keith N. Fargo, Juan Fortea, Hector Gonzalez, Deborah R. Gustafson, Elizabeth Head, James A. Hendrix, Scott M. Hofer, Leigh A. Johnson, Roos Jutten, Kerry Kilborn, Krista L. Lanctot, Jennifer J. Manly, Ralph N. Martins, Michelle M. Mielke, Martha Clare Morris, Melissa E. Murray, Esther S. Oh, Mario A. Parra, Robert A. Rissman, Catherine M. Roe, Octavio A. Santos, Nikolaos Scarmeas, Lon S. Schneider, Nicole Schupf, Sietske Sikkes, Heather M. Snyder, Hamid R. Sohrabi, Yaakov Stern, Andre Strydom, Yi Tang, Graciela Muniz Terrera Muniz Terrera, Yaakov Stern, Andre Strydom, Yi Tang, Graciela Muniz Terrera, Charlotte Teunissen, Debora Melo Van Lent, Michael Weinborn, Linda Wesselman, Donna M. Wilcock, Henrik Zetterberg, Sid E. O’Bryant, International Society To Advance Alzheimer’S Research And Treatment, Alzheimer’S Association

Research outputs 2014 to 2021

Alzheimer's disease and related dementias (ADRDs) are a global crisis facing the aging population and society as a whole. With the numbers of people with ADRDs predicted to rise dramatically across the world, the scientific community can no longer neglect the need for research focusing on ADRDs among underrepresented ethnoracial diverse groups. The Alzheimer's Association International Society to Advance Alzheimer's Research and Treatment (ISTAART; alz.org/ISTAART) comprises a number of professional interest areas (PIAs), each focusing on a major scientific area associated with ADRDs. We leverage the expertise of the existing international cadre of ISTAART scientists and experts to synthesize a …

Hematologic Safety Of Chronic Brain-Penetrating Erythropoietin Dosing In App/Ps1 Mice, Jiahong Sun, Joshua Yang, Kathrine Whitman, Charlene Zhu, David H. Cribbs, Ruben J. Boado, William M. Pardridge, Rachita K. Sumbria

Pharmacy Faculty Articles and Research

Introduction: Low blood-brain barrier (BBB) penetration and hematopoietic side effects limit the therapeutic development of erythropoietin (EPO) for Alzheimer's disease (AD). A fusion protein of EPO and a chimeric monoclonal antibody targeting the mouse transferrin receptor (cTfRMAb) has been engineered. The latter drives EPO into the brain via receptor-mediated transcytosis across the BBB and increases its peripheral clearance to reduce hematopoietic side effects of EPO. Our previous work shows the protective effects of this BBB-penetrating EPO in AD mice but hematologic effects have not been studied. Herein, we investigate the hematologic safety and therapeutic effects of chronic cTfRMAb-EPO dosing, …

Spinal Matrix Metalloproteinase 8 Regulates Pain After Peripheral Trauma, Maral Tajerian, J. David Clark

Publications and Research

It is well documented that pain chronification requires a host of plastic mechanisms at the spinal cord (SC) level, including alterations in neuronal and glial structure and function. Such cellular plasticity necessitates the existence of a plastic extracellular matrix(ECM). Here, we describe a key role for ECM remodeling in the regulation of chronic pain following peripheral injury. Three weeks following tibia fracture in mice, we show increased levels of MMP8 in the SC. Furthermore, we show that the pharmacological or genetic downregulation of MMP8 ameliorates the pain phenotype observed after injury. These results delineate an extracellular mechanism for pain chronification, …

Development Of A Functional Testing Platform For The Sensory Segment Of The Neuromuscular Reflex Arc, Alisha Colon

Electronic Theses and Dissertations

Investigations of human biology and disease have been hindered by the use of animal models. The information obtained from such studies often results in clinically irrelevant results and drug trial failures. Additionally, several governing bodies have been formulating legislation to move away from animal models and toward more ethical and efficient testing platforms for drug discovery and cosmetic research. As an answer to these issues, "body-on-a-chip" systems have been a rapidly developing field which easily recapitulates in vivo functionality, providing a more relevant, repeatable, and ethical testing platform to better predict biology. These systems can be used as human-based testing …

Dna Methylation Of The Clusterin Promoter: Associations With Alzheimer’S Disease Risk And Related Phenotypes, Madeline Peretti

Theses: Doctorates and Masters

Background

In 2017 approximately 50 million people worldwide were living with dementia. With Alzheimer’s disease (AD), accounting for 50-70% of dementia cases making this debilitating disease, with no current effective prevention, treatment or cure, a critical healthcare concern. Genome wide association studies (GWAS) have identified a number of risk genes for late onset AD (LOAD); Apolipoprotein E (APOE), a gene involved in the cholesterol/lipid pathway is considered the gene with the greatest risk. The third most associated AD risk gene is Clusterin (CLU), is also involved in the cholesterol/lipid pathway. CLU has been implicated in both …

Sequence-Specific Extracellular Micrornas Activate Tlr7, Niming Wu

Theses & Dissertations

Toll-like receptors (TLRs) play an important role in the innate immune system. Emerging evidence shows that TLRs, especially endosomal TLRs, can participate in CNS diseases by increasing the production of proinflammatory cytokines via recognition of microRNAs (miRNAs), however which of the miRNAs are able to activate signaling and whether specific sequence motifs are involved remains incompletely defined. Here we found that numerous miRNAs induced TNF-a production across multiple myeloid cell types, including microglia, and that this effect was abolished in cells deficient of TLR7. In particular, miR-20a-5p and miR-148b-3p preferentially stimulate cytokine secretion compared to miR-20b-5p and miR-148a-3p, respectively, despite …

The Migration And Developmental Remodeling Of Intrinsic Interneurons In Visual Thalamus And The Role Of Retinal Signaling., Naomi E. Charalambakis

Electronic Theses and Dissertations

The dorsal lateral geniculate nucleus (dLGN) of the mouse is a model system to study the development of thalamic circuitry. While most studies focus on relay neurons of dLGN, little is known about the factors regulating the development of the other principal cell type, intrinsic interneurons. To date, the targeting and migratory path of dLGN interneurons as well as their morphological development remains unclear. Here we examined whether the migration, structure, and function of interneurons relies on retinal signaling. We took a loss-of-function approach and crossed GAD67-GFP mice, which express green fluorescent protein (GFP) in dLGN interneurons, with math5 nulls …

Cell Specific Control Of The Pallidostriatal Pathway, Shubha Verma '19

Student Publications & Research

Parkinson’s Disease is a neurodegenerative disorder of the basal ganglia. The main cause for Parkinson’s Disease is the depletion of dopamine, a neurotransmitter. The basal ganglia contains four major nuclei: the substantia nigra, the subthalamic nucleus, the external globus pallidus, and the striatum. These nuclei communicate with each other by the use of neurons.

Heat Shock Protein 40 And Immune Function In Altered Gravity, Amber M. Paul, Brooke D. Shepard, Sharmila Bhattacharya

Publications

In space, astronauts are more susceptible to pathogens, viral reactivation and immunosuppression, which poses limits to their health and the mission. Interestingly, during space flight, stress-inducible heat shock proteins (HSP) are robustly induced, and the overexpression of HSPs have been implicated in immune dysregulation, therefore HSPs may be critically involved in regulating immune homeostasis. HSP40/DNAJ1 plays a major role in proper protein translation and folding. Its loss of function has been implicated in susceptibility to microbial infection, while its overexpression has been implicated in autoimmunity, collectively suggesting its complicated, but necessary, role in maintaining immunological function. To determine the role …

Hyperhomocysteinemia As A Risk Factor For Vascular Contributions To Cognitive Impairment And Dementia, Brittani R. Price, Donna M. Wilcock, Erica M. Weekman

Physiology Faculty Publications

Behind only Alzheimer’s disease, vascular contributions to cognitive impairment and dementia (VCID) is the second most common cause of dementia, affecting roughly 10–40% of dementia patients. While there is no cure for VCID, several risk factors for VCID, such as diabetes, hypertension, and stroke, have been identified. Elevated plasma levels of homocysteine, termed hyperhomocysteinemia (HHcy), are a major, yet underrecognized, risk factor for VCID. B vitamin deficiency, which is the most common cause of HHcy, is common in the elderly. With B vitamin supplementation being a relatively safe and inexpensive therapeutic, the treatment of HHcy-induced VCID would seem straightforward; however, …

How Concussions Alter Brain Network Properties: Towards Better Diagnoses Of Concussions, Sara Krehbiel, Joanna R. Wares

Annual Symposium on Biomathematics and Ecology Education and Research

No abstract provided.

The Evidence For The Benefits From Breast Milk In The Neurodevelopment Of Premature Babies – A Review Of The Recent Literature, Danuta Iulia Paduraru

Journal of Mind and Medical Sciences

Introduction. The brain in preterm babies is usually not fully developed and therefore early post-term events can have long-lasting neurodevelopment and cognitive outcomes. It is known that cerebral white matter connectivity is important for later intact cognitive functioning amongst children born very preterm and that breast milk imparts neurotrophic factors. The relationship between breastfeeding and child development is a long and well-studied area, and the evidence in support of breast milk is already substantial. Here we review the recent literature on the topic to establish whether additional evidence is available to strengthen the view that breast milk is superior in …

Thrombospondin Receptor Α2Δ-1 Promotes Synaptogenesis And Spinogenesis Via Postsynaptic Rac1, W. Chris Risher, Namsoo Kim, Sehwon Koh, Ji‑Eun Cho, Petar Mitev, Erin F. Spence, Louis‑Jan Pilaz, Dongqing Wang, Guoping Feng, Debra L. Silver, Scott H. Soderling, Henry H. Yin, Cagla Eroglu

Biomedical Sciences

Astrocytes control excitatory synaptogenesis by secreting thrombospondins (TSPs), which function via their neuronal receptor, the calcium channel subunit α2δ-1. α2δ-1 is a drug target for epilepsy and neuropathic pain; thus the TSP–α2δ-1 interaction is implicated in both synaptic development and disease pathogenesis. However, the mechanism by which this interaction promotes synaptogenesis and the requirement for α2δ-1 for connectivity of the developing mammalian brain are unknown. In this study, we show that global or cell-specific loss of α2δ-1 yields profound deficits in excitatory synapse numbers, ultrastructure, and activity and severely stunts spinogenesis in the mouse cortex. Postsynaptic but not presynaptic α2δ-1 …

New Functions For The Proprioceptive System In Skeletal Biology, Ronen Blecher, Lia Heinemann-Yerushalmi, Eran Assaraf, Nitzan Konstantin, Jens R. Chapman, Timothy C. Cope, Guy S. Bewick, Robert W. Banks, Elazar Zelzer

Neuroscience, Cell Biology & Physiology Faculty Publications

Muscle spindles and Golgi tendon organs (GTOs) are two types of sensory receptors that respond to changes in length or tension of skeletal muscles. These mechanosensors have long been known to participate in both proprioception and stretch reflex. Here, we present recent findings implicating these organs in maintenance of spine alignment as well as in realignment of fractured bones. These discoveries have been made in several mouse lines lacking functional mechanosensors in part or completely. In both studies, the absence of functional spindles and GTOs produced a more severe phenotype than that of spindles alone. Interestingly, the spinal curve phenotype, …