Medical Neurobiology Commons^™

Nsaids Naproxen, Ibuprofen, Salicylate, And Aspirin Inhibit Trpm7 Channels By Cytosolic Acidification, Rikki Chokshi, Orville Bennett, Tetyana Zhelay, J. Ashot Kozak

Neuroscience, Cell Biology & Physiology Faculty Publications

Non-steroidal anti-inflammatory drugs (NSAIDs) are used for relieving pain and inflammation accompanying numerous disease states. The primary therapeutic mechanism of these widely used drugs is the inhibition of cyclooxygenase 1 and 2 (COX1, 2) enzymes that catalyze the conversion of arachidonic acid into prostaglandins. At higher doses, NSAIDs are used for prevention of certain types of cancer and as experimental treatments for Alzheimer’s disease. In the immune system, various NSAIDs have been reported to influence neutrophil function and lymphocyte proliferation, and affect ion channels and cellular calcium homeostasis. Transient receptor potential melastatin 7 (TRPM7) cation channels are highly expressed in …

Identification And Characterization Of Cyps Induced In The Drosophila Antenna By Exposure To A Plant Odorant, Shane R Baldwin, Pratyajit Mohapatra, Monica Nagalla, Rhea Sindvani, Desiree Amaya, Hope A Dickson, Karen Menuz

Department of Medicine Faculty Papers

Degrading Enzymes (ODEs). However, their contribution to olfactory signaling in vivo is poorly understood. This is due in part to the challenge of identifying which of the dozens of antennal-expressed CYPs might inactivate a given odorant. Here, we tested a high-throughput deorphanization strategy in Drosophila to identify CYPs that are transcriptionally induced by exposure to odorants. We discovered three CYPs selectively upregulated by geranyl acetate using transcriptional profiling. Although these CYPs are broadly expressed in the antenna in non-neuronal cells, electrophysiological recordings from CYP mutants did not reveal any changes in olfactory neuron responses to this odorant. Neurons were desensitized …

A Comparison Of Calcium Aggregation And Ultracentrifugation Methods For The Preparation Of Rat Brain Microsomes For Drug Metabolism Studies, Barent N. Dubois, Farideh Amirrad, Reza Mehvar

Pharmacy Faculty Articles and Research

Preparation of brain microsomes by the calcium chloride aggregation method has been suggested as an alternative to the ultracentrifugation method. However, the effects of the calcium chloride concentration on the quality of the microsomal fractions are not known. Brain microsomes were prepared from the adult rat brains using the high-speed ultracentrifugation and low-speed calcium chloride (10–100 mM) aggregation methods (n = 5–6 per group). The microsomal protein yield (spectrometry), the cytochrome P450 reductase (CPR) activity (spectrometry), and the monooxygenase activities (UPLC-MS/MS) of CYP2D and CYP2E1 were determined in the obtained fractions. Increasing the concentrations of calcium chloride progressively increased …

Leveraging High-Resolution 7-Tesla Mri To Derive Quantitative Metrics For The Trigeminal Nerve And Subnuclei Of Limbic Structures In Trigeminal Neuralgia, Judy Alper, Alan C. Seifert, Gaurav Verma, Kuang-Han Huang, Yael Jacob, Ameen Al Qadi, John W. Rutland, Sheetal Patel, Joshua Bederson, Raj K. Shrivastava, Bradley N. Delman, Priti Balchandani

Publications and Research

Background: Trigeminal Neuralgia (TN) is a chronic neurological disease that is strongly associated with neurovascular compression (NVC) of the trigeminal nerve near its root entry zone. The trigeminal nerve at the site of NVC has been extensively studied but limbic structures that are potentially involved in TN have not been adequately characterized. Specifically, the hippocampus is a stress-sensitive region which may be structurally impacted by chronic TN pain. As the center of the emotion-related network, the amygdala is closely related to stress regulation and may be associated with TN pain as well. The thalamus, which is involved in the trigeminal …

Scoping Review: The Empowerment Of Alzheimer’S Disease Caregivers With Mhealth Applications, Eunhee Kim, Andrius Baskys, Anandi V. Law, Moom R. Roosan, Yan Li, Don Roosan

Pharmacy Faculty Articles and Research

Alzheimer’s Disease (AD) is one of the most prevalent neurodegenerative chronic diseases. As it progresses, patients become increasingly dependent, and their caregivers are burdened with the increasing demand for managing their care. Mobile health (mHealth) technology, such as smartphone applications, can support the need of these caregivers. This paper examines the published academic literature of mHealth applications that support the caregivers of AD patients. Following the PRISMA for scoping reviews, we searched published literature in five electronic databases between January 2014 and January 2021. Twelve articles were included in the final review. Six themes emerged based on the functionalities provided …

Placenta-Specific Slc38a2/Snat2 Knockdown Causes Fetal Growth Restriction In Mice, Owen R. Vaughan, Katarzyna Maksym, Elena Silva, Kenneth Barentsen, Russel V. Anthony, Sara L. Hillman, Thomas L. Brown, Rebecca Spencer, Anna L. David, Fredrick J. Rosario, Theresa L. Powell, Thomas Jansson

Neuroscience, Cell Biology & Physiology Faculty Publications

Fetal growth restriction (FGR) is a complication of pregnancy that reduces birth weight, markedly increases infant mortality and morbidity and is associated with later-life cardiometabolic disease. No specific treatment is available for FGR. Placentas of human FGR infants have low abundance of sodium-coupled neutral amino acid transporter 2 (Slc38a2/SNAT2), which supplies the fetus with amino acids required for growth. We determined the mechanistic role of placental Slc38a2/SNAT2 deficiency in the development of restricted fetal growth, hypothesizing that placenta-specific Slc38a2 knockdown causes FGR in mice. Using lentiviral transduction of blastocysts with a small hairpin RNA (shRNA), we achieved 59% knockdown of …

Childhood Exposure To Per- And Polyfluoroalkyl Substances (Pfas) And Neurobehavioral Domains In Children At Age 8 Years, Ann M. Vuong, Kimberly Yolton, Changchun Xie, Kim N. Dietrich, Joseph M. Braun, Glenys M. Webster, Antonia M. Calafat, Bruce P. Lanphear, Aimin Chen

Environmental & Occupational Health Faculty Publications

Background: Toxicological studies have raised concerns regarding the neurotoxic effects of per- and polyfluoroalkyl substances (PFAS). However, observational evidence from human studies investigating the association between childhood PFAS and neurobehavior is limited and remains unclear. Objectives: To examine whether childhood PFAS concentrations are associated with neurobehavior in children at age 8 years and whether child sex modifies this relationship. Methods: We used data from 208 mother-child dyads in the Health Outcomes and Measures of the Environment (HOME) Study, a prospective pregnancy and birth cohort (Cincinnati, OH, USA). We quantified PFAS in child serum at 3 and 8 years. We assessed …

Characterizing The Heterogeneity Of Adult-Onset Leukoencephalopathy With Axonal Spheroids: A Digital Spatial Profiling Study, Peter Liu

Undergraduate Student Research Internships Conference

Adult-onset leukoencephalopathy with axonal spheroids (ALAS) is a group of hereditary, progressive, neurodegenerative disorders involving primarily the central nervous system white matter (WM). ALAS is characterized by patchy, asymmetrical myelin loss and axonal destruction in the WM, predominantly involving the frontoparietal regions. However, the asymmetrical and heterogenous involvement of different brain regions remains poorly characterized.

In this study, digital spatial profiling was performed to investigate the region-specific expressions of 60 proteins. Conventional immunohistochemistry methods was used validate intrepretation of probes. Using a high-plex and high-throughput method, we provide evidence of regional heterogeneity in ALAS, particularly involving key markers of microglia …

Dimensionality Reduction For Classification Of Object Weight From Electromyography, Elnaz Lashgari, Uri Maoz

Psychology Faculty Articles and Research

Electromyography (EMG) is a simple, non-invasive, and cost-effective technology for measuring muscle activity. However, multi-muscle EMG is also a noisy, complex, and high-dimensional signal. It has nevertheless been widely used in a host of human-machine-interface applications (electrical wheelchairs, virtual computer mice, prosthesis, robotic fingers, etc.) and, in particular, to measure the reach-and-grasp motions of the human hand. Here, we developed an automated pipeline to predict object weight in a reach-grasp-lift task from an open dataset, relying only on EMG data. In doing so, we shifted the focus from manual feature-engineering to automated feature-extraction by using pre-processed EMG signals and thus …

Insights Into The Mechanisms Of Brain Endothelial Erythrophagocytosis, Jiahong Sun, Prema Vyas, Samar Mann, Annlia Paganini-Hill, Ane C. F. Nunes, Wei Ling Lau, David H. Cribbs, Mark J. Fisher, Rachita K. Sumbria

Pharmacy Faculty Articles and Research

The endothelial cells which form the inner cellular lining of the vasculature can act as non-professional phagocytes to ingest and remove emboli and aged/injured red blood cells (RBCs) from circulation. We previously demonstrated an erythrophagocytic phenotype of the brain endothelium for oxidatively stressed RBCs with subsequent migration of iron-rich RBCs and RBC degradation products across the brain endothelium in vivo and in vitro, in the absence of brain endothelium disruption. However, the mechanisms contributing to brain endothelial erythrophagocytosis are not well defined, and herein we elucidate the cellular mechanisms underlying brain endothelial erythrophagocytosis. Murine brain microvascular endothelial cells (bEnd.3 …

Medical Schools Ignore The Nature Of Consciousness At Great Cost, Anoop Kumar

Journal of Wellness

The essential question of the relationship between consciousness and matter is ignored in medical school curricula, leading to a machine-like view of the human being that contributes to physician burnout and intellectual dissatisfaction. The evidence suggesting that the brain may not be the seat of consciousness is generally ignored to preserve the worldview of the primacy of matter. By investigating new frameworks detailing the nature of consciousness at different levels of hierarchy, we can bring intellectual rigor to a once opaque subject that supports a fundamental reality about our experience: We are human beings, not only human bodies.

Current State Of Preeclampsia Mouse Models: Approaches, Relevance, And Standardization, Christopher A. Waker, Melissa R. Kaufman, Thomas L. Brown

Neuroscience, Cell Biology & Physiology Faculty Publications

Preeclampsia (PE) is a multisystemic, pregnancy-specific disorder and a leading cause of maternal and fetal death. PE is also associated with an increased risk for chronic morbidities later in life for mother and offspring. Abnormal placentation or placental function has been well-established as central to the genesis of PE; yet much remains to be determined about the factors involved in the development of this condition. Despite decades of investigation and many clinical trials, the only definitive treatment is parturition. To better understand the condition and identify potential targets preclinically, many approaches to simulate PE in mice have been developed and …

Poster: Sars-Cov-2 Neuroinvasion, Heather M. Tatusko

Nursing Student Class Projects (Formerly MSN)

Over the last century, science and literature has reported neurological manifestations during various disease outbreaks as well as long-term sequelae following epidemics and pandemics. Some of the first neurological symptoms reported with Coronavirus Disease 2019 (COVID-19; caused by severe acute respiratory syndrome coronavirus 2 [SARS-Cov-2]) were anosmia and dysgeusia, suggesting SARS-CoV-2 penetrance of the central nervous system (CNS). To date, the definite clinical and pathological basis of CNS involvement of SARS-CoV-2 remains poorly understood, with the neurovirulence of SARS-CoV-2 and its neuroinvasive potential remaining largely unknown. The author’s poster will explore neurological manifestations of COVID-19 disease, the direct and indirect …

Effects Of Genetics And Sex On Hippocampal Gene Expression And Adolescent Behaviors Following Neonatal Ethanol Exposure In Bxd Recombinant Inbred Mice, Jessica A. Baker

Theses and Dissertations (ETD)

Fetal alcohol spectrum disorders (FASD) are the leading preventable neurodevelopmental disorders in the western world. A hallmark symptom of FASD is cognitive and learning deficits that present in early childhood and continue throughout adulthood. Teratogenic effects of alcohol include increased cell death in the hippocampus, a brain region critically important in learning and memory. Genetics have been shown to have a role in the severity of alcohol’s teratogenic effect on the developing brain. Previous work in our lab identified differential vulnerability to ethanol-induced call death in the hippocampus using fourteen BXD strains and the two parental strains. The goal of …

The Role Of Action Potential Waveform In Failure Of Excitation Contraction Coupling, Xueyong Wang, Murad Nawaz, Steve R.A. Burke, Roger Bannister, Brent D. Foy, Andrew A. Voss, Mark M. Rich

Neuroscience, Cell Biology & Physiology Faculty Publications

Excitation contraction coupling (ECC) is the process by which electrical excitation of muscle is converted into force generation. Depolarization of skeletal muscle resting potential contributes to failure of ECC in diseases such as periodic paralysis, ICU acquired weakness and possibly fatigue of muscle during vigorous exercise. When extracellular K+ is raised to depolarize the resting potential, failure of ECC occurs suddenly, over a range of several mV of resting potential. While some studies have hypothesized the sudden failure of ECC is due to all-or-none failure of excitation, other studies suggest failure of excitation is graded. Intracellular recordings of action potentials …

Immunological And Hematological Outcomes Following Protracted Low Dose/Low Dose Rate Ionizing Radiation And Simulated Microgravity, Amber M. Paul, Eliah G. Overbey, Willian A. Da Silveira, Nathaniel Szewczyk, Nina C. Nishiyama, Michael J. Pecaut, Sulekha Anand, Jonathan M. Galazka, Xiao Wen Mao

Publications

Using a ground-based model to simulate spaceflight [21-days of single-housed, hindlimb unloading (HLU) combined with continuous low-dose gamma irradiation (LDR, total dose of 0.04 Gy)], an in-depth survey of the immune and hematological systems of mice at 7-days post-exposure was performed. Collected blood was profiled with a hematology analyzer and spleens were analyzed by whole transcriptome shotgun sequencing (RNA-sequencing). The results revealed negligible differences in immune differentials. However, hematological system analyses of whole blood indicated large disparities in red blood cell differentials and morphology, suggestive of anemia. Murine Reactome networks indicated majority of spleen cells displayed differentially expressed genes (DEG) …

Machine Learning Classification Of Traumatic Brain Injury Patients Versus Healthy Controls Using Arterial Spin Labeled Perfusion Mri, Vanessa I. Grass

Dissertations, Theses, and Capstone Projects

Traumatic brain injury (TBI) is one of the most common causes of death and disability worldwide, yet accurate in vivo detection of TBI neuropathology remains challenging due to complexities in the structural and functional changes observed post-injury as well as limitations in conventional neuroimaging modalities. Although advanced neuroimaging techniques such as arterial spin labeling (ASL) can noninvasively assess cerebral blood flow (CBF) changes observed post-injury, this technique is underutilized in TBI research partly due to the low signal-to-noise-ratio (SNR) inherent in ASL imaging. The aim of the current study is to examine the use of machine learning, specifically a Support …

Explicit Training To Improve Affective Prosody Recognition In Adults With Acute Right Hemisphere Stroke, Alexandra Zezinka Durfee, Shannon M. Sheppard, Erin L. Meier, Lisa Bunker, Erjia Cui, Ciprian Crainiceanu, Argye E. Hillis

Communication Sciences and Disorders Faculty Articles and Research

Difficulty recognizing affective prosody (receptive aprosodia) can occur following right hemisphere damage (RHD). Not all individuals spontaneously recover their ability to recognize affective prosody, warranting behavioral intervention. However, there is a dearth of evidence-based receptive aprosodia treatment research in this clinical population. The purpose of the current study was to investigate an explicit training protocol targeting affective prosody recognition in adults with RHD and receptive aprosodia. Eighteen adults with receptive aprosodia due to acute RHD completed affective prosody recognition before and after a short training session that targeted proposed underlying perceptual and conceptual processes. Behavioral impairment and lesion characteristics were …

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 …

Implementation Of A National Telestroke Program: A Unit-Based Staff Education Inititative, Leigh Ann Raymond

Master of Science in Nursing Scholarly Project

Abstract

A national telestroke program (NTSP) was implemented at a medical center in the latter half of 2020. Following two inpatient strokes, it was discovered that only 67 members of the 370-member inpatient nursing staff had been assigned the required online learning modules. A unit-based nursing educational initiative was developed utilizing available online learning modules to address the gaps in knowledge in recognizing acute stroke signs, symptoms and providing timely care. The educational initiative, however, supplemented and complimented the online learning modules by incorporating an in-person poster presentation on inpatient strokes that included a small group discussion of an inpatient …