Hematologic Safety Of Chronic Brain-Penetrating Erythropoietin Dosing In App/Ps1 Mice,
2019
Keck Graduate Institute
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,
2019
CUNY Queens College
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,
2019
University of Central Florida
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 …
Perspectives On Ethnic And Racial Disparities In Alzheimer's Disease And Related Dementias: Update And Areas Of Immediate Need,
2019
Edith Cowan University
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 …
Axon Initial Segment Integrity In Aging And Traumatic Brain Injury,
2019
Virginia Commonwealth University
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 …
Sequence-Specific Extracellular Micrornas Activate Tlr7,
2018
University of Nebraska Medical Center
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.,
2018
University of Louisville
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,
2018
Illinois Mathematics and Science Academy
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.
Hyperhomocysteinemia As A Risk Factor For Vascular Contributions To Cognitive Impairment And Dementia,
2018
University of Kentucky
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, …
Heat Shock Protein 40 And Immune Function In Altered Gravity,
2018
NASA Ames Research Center, Universities Space Rsearch Association
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 …
How Concussions Alter Brain Network Properties: Towards Better Diagnoses Of Concussions,
2018
University of Richmond
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,
2018
Manzanares Health Center, Ciudad Real, España
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,
2018
Marshall University
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,
2018
Weizmann Institute of Science Israel
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, …
In Vivo Brainstem Imaging In Alzheimer’S Disease: Potential For Biomarker Development,
2018
University of Kentucky
In Vivo Brainstem Imaging In Alzheimer’S Disease: Potential For Biomarker Development, David J. Braun, Linda J. Van Eldik
Neuroscience Faculty Publications
The dearth of effective treatments for Alzheimer’s disease (AD) is one of the largest public health issues worldwide, costing hundreds of billions of dollars per year. From a therapeutic standpoint, research efforts to date have met with strikingly little clinical success. One major issue is that trials begin after substantial pathological change has occurred, and it is increasingly clear that the most effective treatment regimens will need to be administered earlier in the disease process. In order to identify individuals within the long preclinical phase of AD who are likely to progress to dementia, improvements are required in biomarker development. …
Brain Endothelial Erythrophagocytosis And Hemoglobin Transmigration Across Brain Endothelium: Implications For Pathogenesis Of Cerebral Microbleeds,
2018
Keck Graduate Institute
Brain Endothelial Erythrophagocytosis And Hemoglobin Transmigration Across Brain Endothelium: Implications For Pathogenesis Of Cerebral Microbleeds, Rudy Chang, Juan Castillo, Alexander C. Zambon, Tatiana B. Krasieva, Mark J. Fisher, Rachita K. Sumbria
Pharmacy Faculty Articles and Research
Peripheral endothelial cells are capable of erythrophagocytosis, but data on brain endothelial erythrophagocytosis are limited. We studied the relationship between brain endothelial erythrophagocytosis and cerebral microhemorrhage, the pathological substrate of MRI-demonstrable cerebral microbleeds. To demonstrate the erythrophagocytic capability of the brain endothelium, we studied the interactions between brain endothelial cells and red blood cells exposed to oxidative stress in vitro, and developed a new in vitro cerebral microbleeds model to study the subsequent passage of hemoglobin across the brain endothelial monolayer. Using multiple approaches, our results show marked brain endothelial erythrophagocytosis of red blood cells exposed to oxidative stress compared …
Repetitive Transcranial Electrical Stimulation Induces Quantified Changes In Resting Cerebral Perfusion Measured From Arterial Spin Labeling,
2018
Wright State University - Main Campus
Repetitive Transcranial Electrical Stimulation Induces Quantified Changes In Resting Cerebral Perfusion Measured From Arterial Spin Labeling, Matthew Sherwood, Aaron T. Madaris, Casserly R. Mullenger, R. Andy Mckinley
Neuroscience, Cell Biology & Physiology Faculty Publications
The use of transcranial electrical stimulation (TES) as a method to augment neural activity has increased in popularity in the last decade and a half. The specific application of TES to the left prefrontal cortex has been shown to produce broad cognitive effects; however, the neural mechanisms underlying these effects remain unknown. In this work, we evaluated the effect of repetitive TES on cerebral perfusion. Stimulation was applied to the left prefrontal cortex on three consecutive days, and resting cerebral perfusion was quantified before and after stimulation using arterial spin labeling. Perfusion was found to decrease significantly more in a …
Pathogenicity And Protection Mediated By A Single Tcrβ In Experimental Autoimmune Encephalomyelitis,
2018
University of Tennessee Health Science Center
Pathogenicity And Protection Mediated By A Single Tcrβ In Experimental Autoimmune Encephalomyelitis, Tianhua Wu
Theses and Dissertations (ETD)
How the TCR repertoire, together with risk-associated major histocompatibility complex (MHC), imposes susceptibility for autoimmune disease is not fully understood. A small fraction of TCR α or β chains are “public”, and are shared by most individuals.High-throughput sequencing of the mouse TCRβ repertoire during myelin oligodendrocyte glycoprotein (MOG)-induced experimental autoimmuneencephalomyelitis (EAE) identified a public TCRβ chain, TCRβ1, which was highly shared among individual mice and preferentially deployed during EAE. Retrogenic expression of TCRβ1 resulted in spontaneous early-onset EAE in mice with high penetrance and severity, despite being paired with a diverse endogenous TCRα repertoire. To further study autoimmunity conferred by …
The Role Of Developmental Timing Regulators In Progenitor Proliferation And Cell Fate Specification During Mammalian Neurogenesis,
2018
Rowan University
The Role Of Developmental Timing Regulators In Progenitor Proliferation And Cell Fate Specification During Mammalian Neurogenesis, Jennifer S. Romer-Seibert
Graduate School of Biomedical Sciences Theses and Dissertations
Developmental timing is a key aspect of tissue and organ formation in which distinct cell types are generated through a series of steps from common progenitors. These progenitors undergo specific changes in gene expression that signifies both a distinct progenitor type and developmental time point that thereby specifies a particular cell fate at that stage of development. The nervous system is an important setting for understanding developmental timing because different cell types are produced in a certain order and the switch from stem cells to progenitors requires precise timing and regulation. Notable examples of such regulatory molecules include the RNA-binding …
Gender- And Region-Specific Changes In Estrogen Signaling In Aging Rat Brain Mitochondria,
2018
Wright State University - Main Campus
Gender- And Region-Specific Changes In Estrogen Signaling In Aging Rat Brain Mitochondria, Christopher M. Evola, Tanner L. Hudson, Luping Huang, Adrian M. Corbett, Debra A. Mayes
Neuroscience, Cell Biology & Physiology Faculty Publications
Recently epidemiological studies suggest females lose neuroprotection from neurodegenerative diseases as they go through menopause. It has been hypothesized that this neuroprotection is hormone‐dependent. The current study characterized cell signaling molecules downstream of estrogen receptor beta that are known to play a role in memory, PKC, ERK, and connexin‐43, in regions of the brain associated with memory decline in an attempt to elucidate significant changes that occur post‐estrus. Total whole cell lysates were compared to isolated mitochondrial protein because mitochondrial function is known to be altered during aging. As hypothesized, protein concentrations differed depending on age, gender, and brain region. …
