Nervous System Diseases Commons^™

Considerations In The Management Of Juvenile Absence Epilepsy In Pregnancy And In Females Of Childbearing Age, Casey Brew

Capstone Showcase

JAE is an epilepsy syndrome that typically requires lifelong AED treatment, and valproic acid or lamotrigine is considered first line to manage the spectrum of associated seizures. In females with JAE who become pregnant, there exist risks both from having uncontrolled seizures and from taking AEDs during the pregnancy. Valproic acid carries the highest risks to the fetus but is the most effective in controlling the seizure types seen with JAE. Folic acid supplementation has shown to mitigate some but not all of the fetal risks from valproic acid. Limited guidance from professional organizations exists for management of females of …

Fatty Acid Therapy And Implications For Spinal Cord Injury Treatment: A Literature Review, Philippe J. Dentino

MEDI 9331 Scholarly Activities Clinical Years

Introduction: Spinal Cord Injuries (SCI) are catastrophic injury to spinal neurons that cause a tremendous socioeconomic and public health burden on individuals globally. The role of fatty acids in treatment of SCI is not well understood and poorly standardized across treatment provision. This review seeks to explore the role of fatty acids in neurorecovery and propose emerging themes in SCI treatment with fatty acids.

Methods: A PICO was designed and online databases were searched for relevant articles. A total of 55 studies were deemed appropriate for the review and summarized into thematic elements including ) Cellular Transport 2) Neuroprotection 3) …

Brain Glycogen – Beyond Energy Storage In Glycogen Storage Diseases, Kia H. Markussen

Theses and Dissertations--Molecular and Cellular Biochemistry

Glycogen is a carbohydrate molecule that is traditionally viewed as a convenient and easily accessible energy storage form of glucose. However,emerging evidence supports the role of glycogen as more than a glucose storage form. During the last 20 years, glycogen has been shown to play pivotal roles in learning and memory, signaling events, viscosity, protein glycosylation, and be acritical hallmark in devastating diseases. Not only, does glycogen play a role as an energy substrate and critical metabolite during energy deprivation, glycogen is central for neurotransmitter homeostasis, tumor initiation, and ontributes to proper protein glycosylation in the brain. In this work, …

Glial Cell-Specific Contribution Of Pkr-Like Er Kinase (Perk) In Neuroinflammation And Behavior, Anirudhya Lahiri

Graduate Theses, Dissertations, and Problem Reports (ETD)

Neurological disorders such as multiple sclerosis (MS) are a major public health concern in the US, with no available therapeutic cure. Chronic neuroinflammation and aberrant proteostasis in the central nervous system (CNS) are the major hallmarks of neurological diseases. Endoplasmic Reticulum (ER) is a major cellular organelle involved in protein synthesis, folding and maturation of various secretory and transmembrane proteins. Pathophysiological stressors such as trauma and infection result in misfolded protein accumulation in the endoplasmic reticulum (ER) lumen, which results in ER stress. To regain proteostasis (protein homeostasis), cells activate the unfolded protein response (UPR). UPR is an evolutionarily conserved …

Subcortical Functional Connectivity And Its Association With Walking Performance Following Deployment Related Mild Tbi, Mary R Newsome, Sarah L Martindale, Nicholas Davenport, Emily L Dennis, Marlene Diaz, Carrie Esopenko, Cooper Hodges, George R Jackson, Qisheng Liu, Kimbra Kenney, Andrew R Mayer, Jared A Rowland, Randall S Scheibel, Joel L Steinberg, Brian A Taylor, David F Tate, J Kent Werner, William C Walker, Elisabeth A Wilde

Faculty, Staff and Students Publications

INTRODUCTION: The relation between traumatic brain injury (TBI), its acute and chronic symptoms, and the potential for remote neurodegenerative disease is a priority for military research. Structural and functional connectivity (FC) of the basal ganglia, involved in motor tasks such as walking, are altered in some samples of Service Members and Veterans with TBI, but any behavioral implications are unclear and could further depend on the context in which the TBI occurred.

METHODS: In this study, FC from caudate and pallidum seeds was measured in Service Members and Veterans with a history of mild TBI that occurred during combat deployment, …

Vulnerability And Adaptation Of Neocortical Neuron Subtypes In Models Of Concussive Traumatic Brain Injury And Multiple Sclerosis, Alan C. Harris Jr.

Theses and Dissertations

The pathognomonic sequela of traumatic brain injury is traumatic axonal injury, the

burden of which correlates with less favorable outcomes. Elucidation of

the intrinsic variables that endow delineated neuronal subgroups and microanatomical domains with outsized vulnerability to injury represents a critical domain of inquiry toward the successful translation of disease-modifying therapeutics. To this end, we studied mild traumatic brain injury (mTBI) within the central fluid percussion model to examine the consequences of mTBI on the morphology and functional integrity of the axon initial segment (AIS) and the relative contributions to network homeostasis mediated by distinct populations of inhibitory interneurons. One …

Seizures, Vitamin D Deficiency, And Severe Hypophosphatemia: The Unique Presentation Of A Sars-Cov-2 Case, Benson Yeh, Christopher Bell, Christopher Anderson, Mack Sheraton

Faculty, Staff and Student Publications

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a virus that belongs to the species severe acute respiratory syndrome-related coronavirus (SARSr-CoV), which is related to the SARS-CoV-1 virus that caused the 2002-2004 SARS outbreak. SARS-CoV-2 causes coronavirus disease 2019 (COVID-19). It has been associated with electrolyte abnormalities. In this report, we discuss the case of a SARS-CoV-2-infected person presenting with recurrent seizure episodes resulting from hypophosphatemia. A 52-year-old male patient with questionable prior seizure history presented to the emergency department (ED) twice within eight days with recurring seizure episodes. While the physical examination at the first presentation was significant for …

Accelerated Forgetting In People With Epilepsy: Pathologic Memory Loss, Its Neural Basis, And Potential Therapies, Sarah Ashley Steimel Phd

Dartmouth College Ph.D Dissertations

While forgetting is vital to human functioning, delineating between normative and disordered forgetting can become incredibly complex. This thesis characterizes a pathologic form of forgetting in epilepsy, identifies a neural basis, and investigates the potential of stimulation as a therapeutic tool. Chapter 2 presents a behavioral characterization of the time course of Accelerated Long-Term Forgetting (ALF) in people with epilepsy (PWE). This chapter shows evidence of ALF on a shorter time scale than previous studies, with a differential impact on recall and recognition. Chapter 3 builds upon the work in Chapter 2 by extending ALF time points and investigating the …

How To Manage The Initiation Of Apomorphine Therapy Without Antiemetic Pretreatment: A Review Of The Literature, Stuart H. Isaacson, Richard B. Dewey, Rajesh Pahwa, Daniel E. Kremens

Department of Neurology Faculty Papers

Introduction

Pretreatment with the antiemetic trimethobenzamide has been recommended practice in the United States (US) to address the risk of nausea and vomiting during initiation of apomorphine treatment. However, trimethobenzamide is no longer being manufactured in the US, and despite the recent update to the US prescribing information, there may be uncertainty regarding how to initiate apomorphine.

Methods

To better understand why antiemetic pretreatment was recommended and if it is necessary when initiating apomorphine therapy, we performed a literature review of subcutaneous apomorphine therapy initiation with and without antiemetic pretreatment in patients with PD.

Results

Three studies were identified as …

Exploring Risk Factors Of Alzheimer’S Disease Using Mouse Models, Xian Han

Theses and Dissertations (ETD)

Mouse models of Alzheimer’s disease (AD) that accurately recapitulate pathology and molecular changes are crucial for understanding disease mechanisms and subsequent therapeutic development. We examined five commonly used mouse models of AD (5xFAD, J20, APPNL-F, APPNL-G-F, Tau P301S) and compared their whole- and phosphoproteomes with human AD (the integration of three published datasets) to study whether they can mimic protein/RNA expression discrepancies, molecular changes, and enriched pathways found in human AD cases. The mouse models especially 5xFAD and APPNL-G-F show proteomic signatures similar to human AD but lack human-specific AD progressions, such as dysregulation of synaptic pathways and networks. Integration …

Med12 Is A Critical Regulator Of Neural Crest Lineage And Nervous System Myelination, Fatma Betul Aksoy Yasar

Dissertations and Theses (Open Access)

The Mediator complex (MED) is a multi-subunit protein complex integral to the eukaryotic transcription machinery. MED12 is a Cdk8- regulatory kinase module subunit directly implicated in human disease and is genetically altered in neurological disease and cancer. Numerous attempts at generating an in vivo system to study the role of Med12 failed due to embryonic lethality associated with germline or developmental disruption of Med12 gene. To understand the cellular and molecular processes associated with its role in disease, we generated multiple mouse models with targeted depletion of MED12 in distinct cellular lineages. Our genetically engineered models with induced and conditional …

The Uncertainty And Psychological Health Of Family Caregivers Of Patients With Delirium In Intensive Care Units, Amal Shokri Haji Assa

Theses and Dissertations (ETD)

Each year, more than 5 million patients are admitted to an intensive care unit (ICU) in the United States, and up to 80 % of these patients develop delirium. Delirium is a common indicator of acute brain dysfunction in the ICU and a predictor of mortality, longer ICU/hospital stay, and long-term cognitive impairment. Family caregivers are a valuable resource in preventing, detecting, and managing delirium in the ICU. However, witnessing delirium episodes can generate adverse psychological symptoms in family caregivers that may compromise their health and well-being. Research in this area has demonstrated a gap in the literature regarding how …

Defining The Impact Of Clinically Modeled Hindlimb Stretching, Exercise, & Inactivity On Functional Recovery After Spinal Cord Injury., Greta Cesarz

Electronic Theses and Dissertations

Spinal cord injury (SCI) is a devastating, life altering event that affects approximately 282,000 Americans. The most obvious side effect of SCI is paralysis due to damage to the spinal cord that disrupts ascending and descending pathways as well as central pattern generating circuitry. In addition to paralysis, patients suffer from other debilitating side effects including altered cardiovascular function, autonomic dysreflexia, neuropathic pain, spasticity, and contractures. In contrast to humans, rodents display spontaneous locomotor recovery following incomplete SCI due to in-cage activity/training. Previously, our laboratory has studied the effect of lack of in-cage training by utilizing custom designed rodent wheelchairs. …

Endovascular Repair Of Intercostal Patch Aneurysms In A Patient With Loyes-Dietz Syndrome, Guilherme B Lima, Laura Ocasio, Marina Dias-Neto, Emanuel R Tenorio, Thanila A Macedo, Gustavo S Oderich

Faculty, Staff and Student Publications

No abstract provided.

Massive Macroglossia, A Rare Side Effect Of Covid-19: Clinical, Histologic, And Genomic Findings In Covid-19-Positive Versus Covid-19-Negative Patients, Victoria A Mañón, David Chubb, Laura S Farach, Rachid Karam, Mary C Farach-Carson, Nadarajah Vigneswaran, Karan Saluja, Simon Young, Mark Wong, James C Melville

Faculty, Staff and Student Publications

PURPOSE: The primary purpose of this study is to identify if there is an underlying genetic predisposition for COVID-related macroglossia and if this susceptibility is higher among individuals of African heritage. Secondary objectives include determining if genetic testing of COVID-infected patients who are intubated and prone could identify patients with higher susceptibility to the development of macroglossia.

METHODS: A retrospective chart review was completed for each patient, and prospectively, genetic and histopathologic analyses were completed. Whole-exome sequencing was completed on two patients; immunohistochemistry was completed on the COVID-positive tissue samples.

RESULTS: Histopathology of the COVID-positive patient revealed significant peri-lymphocytic infiltrate, …

Understanding Parkinson’S Disease Through Gait Initiation And Center Of Pressure, Mira Ananthanarayanan, Kiara Salceda, Michael Shiraishi, Rahul Soangra

Student Scholar Symposium Abstracts and Posters

Parkinson's disease is a neurological disorder that causes tremors and freezing of gait in diagnosed patients. Freezing of gait can be difficult to identify and intervene without laboratory based instruments data collection. Force plates have been proven to show viable results in identifying gait events such as heel contact and toe off. The complete gait cycle consists of a right-heel strike, right heel-to-toe shift, simultaneous right-toe off/left heel strike, left heel-to-toe shift, and a simultaneous left-toe off/right heel strike. This study will investigate center of pressure trajectories when initiating gait between healthy and Parkinson's participants. It is predicted that the …

Identifying Voice-Based Digital Biomarkers Of Parkinson's Disease, Rachelle Beshay, Madison Gill, Michael Shiraishi, Rahul Soangra

Student Scholar Symposium Abstracts and Posters

Introduction: Parkinson's disease is a disorder in the central nervous system that causes tremors, abnormal gait and balance, and muscle rigidity due to loss of function in parts of the brain. Traditionally, Parkinson's is identified by the physical symptoms seen in a patient's gait and motor skills, but irregular speech patterns (hypokinetic dysarthria) is one of the first symptoms to be derived from the disease. Objective: The goal of this ongoing study is to use Mel Frequency Centrum Coefficients (MFCC), to diagnose Parkinson's in the early stages by identifying hypokinetic dysarthria. MFCC's process speech recognition patterns and produce …

Effects Of Transcranial Direct Current Stimulation On Adults With Post-Acute Covid-19 Syndrome, Isaac Min, Aaron Schurger

Student Scholar Symposium Abstracts and Posters

Since its detection in December 2019, coronavirus disease 2019 (COVID-19), the viral disease caused by the SARS-CoV-2 novel coronavirus, has had prominent effects on human health and mortality. Studies in previous infections of SARS-CoV and MERS-CoV have found evidence of persistent symptoms in recovered patients, such as lethargy and shortness of breath. Similar residual symptoms have also been seen in recovered COVID-19 patients beyond four weeks of the initial onset of symptoms — collectively termed post-acute COVID-19 syndrome (PACS). These symptoms include deficits in working memory. Preliminary studies done in the United States and Europe have shown a significant portion …

Delta Oscillation Coupled Propagating Fast Ripples Precede Epileptiform Discharges In Patients With Focal Epilepsy, Shennan A. Weiss, Laurent Sheybani, Nitish Seenarine, Itzhak Fried, Chengyuan Wu, Ashwini Sharan, Jerome Engel Jr., Michael R. Sperling, Yuval Nir, Richard J. Staba

Department of Neurology Faculty Papers

Epileptiform spikes are used to localize epileptogenic brain tissue. The mechanisms that spontaneously trigger epileptiform discharges are not yet elucidated. Pathological fast ripple (FR, 200–600 Hz) are biomarkers of epileptogenic brain, and we postulated that FR network interactions are involved in generating epileptiform spikes. Using macroelectrode stereo intracranial EEG (iEEG) recordings from a cohort of 46 patients we found that, in the seizure onset zone (SOZ), propagating FR were more often followed by an epileptiform spike, as compared with non-propagating FR (p < 0.05). Propagating FR had a distinct frequency and larger power (p < 1e-10) and were more strongly phase coupled to the peak of iEEG delta oscillation, which likely correspond with the DOWN states during non-REM sleep (p < 1e-8), than non-propagating FR. While FR propagation was rare, all FR occurred with the highest probability within +/− 400 msec of epileptiform spikes with superimposed high-frequency oscillations (p < 0.05). Thus, a sub-population of epileptiform spikes in the SOZ, are preceded by propagating FR that are coordinated by the DOWN state during non-REM sleep.

Individualised Prediction Of Drug Resistance And Seizure Recurrence After Medication Withdrawal In People With Juvenile Myoclonic Epilepsy: A Systematic Review And Individual Participant Data Meta-Analysis, Remi Stevelink, Dania Al-Toma, Floor E. Jansen, Herm J. Lamberink, Ali A. Asadi-Pooya, Mohsen Farazdaghi, Gonçalo Cação, Sita Jayalakshmi, Anuja Patil, Çiğdem Özkara, Şenay Aydın, Joanna Gesche, Christoph P. Beier, Linda J. Stephen, Martin J. Brodie, Gopeekrishnan Unnithan, Ashalatha Radhakrishnan, Julia Höfler, Eugen Trinka, Roland Krause, Emanuele Cerulli Irelli, Carlo Di Bonaventura, Jerzy P. Szaflarski, Laura E. Hernández-Vanegas, Monica L. Moya-Alfaro, Yingying Zhang, Dong Zhou, Nicola Pietrafusa, Nicola Specchio, Giorgi Japaridze, Sándor Beniczky, Mubeen Janmohamed, Patrick Kwan, Marte Syvertsen, Kaja K. Selmer, Bernd J. Vorderwülbecke, Martin Holtkamp, Lakshminarayanapuram G. Viswanathan, Sanjib Sinha, Betül Baykan, Ebru Altindag, Felix Von Podewils, Juliane Schulz, Udaya Seneviratne, Alejandro Viloria-Alebesque, Ioannis Karakis, Wendyl J. D'Souza, Josemir W. Sander, Bobby P. C. Koeleman, Willem M. Otte, Kees P. J. Braun

Department of Neurology Faculty Papers

BACKGROUND: A third of people with juvenile myoclonic epilepsy (JME) are drug-resistant. Three-quarters have a seizure relapse when attempting to withdraw anti-seizure medication (ASM) after achieving seizure-freedom. It is currently impossible to predict who is likely to become drug-resistant and safely withdraw treatment. We aimed to identify predictors of drug resistance and seizure recurrence to allow for individualised prediction of treatment outcomes in people with JME.

METHODS: We performed an individual participant data (IPD) meta-analysis based on a systematic search in EMBASE and PubMed - last updated on March 11, 2021 - including prospective and retrospective observational studies reporting on …

Living With Multiple Sclerosis As A Former Marathon Runner: Impact Of Attitude And Past Behaviour On Self-Care Maintenance And Perseverance, Michael Stephanou

Patient Experience Journal

As healthcare professionals, we have a duty to promote the wellbeing of individuals living with chronic diseases and this could be accomplished through the establishment of self-care strategies that are both collaborative and self-directed. Insight into the complex behaviours and backgrounds of individuals who show initiative in dealing with chronic disease could help achieve this by revealing drivers of health-seeking and engaging behaviours. Therefore, by deducing the complex interactions between attitude, past experiences and disease outlook, broader patient welfare could be championed through the implementation of targeted interventions which promote self-care in chronic disease. This article aims to explore these …

Living With Brain Cancer: From Researcher To Patient, Stephen P. Chelko, Daniel L. Fay Ph.D.

Patient Experience Journal

As an academic researcher, my work-life revolves around testing the efficaciousness of pharmaceutical drugs on the prevention of cardiac dysfunction, arrhythmias, and sudden cardiac death in animal models of heart disease. I never thought I would go from someone studying a life-threatening disease to a patient living with one in twenty-four hours. Yet, that transformation occurred October 8, 2019. I was just appointed to Assistant Professor at Johns Hopkins University School of Medicine (JHUSOM), yet after sitting for my professional headshot I had a grand mal seizure. I cannot recall this event, but I bit the tip of my tongue …

What Do We Know So Far About Ofatumumab For Relapsing Multiple Sclerosis? A Meta-Analytical Study, Hafiza Munazza Taj, Maryam Talib, Sania Siddiqa, Azza Sarfraz, Zouina Sarfraz, Karla Robles-Velasco, Ivan Cherrez-Ojeda

Department of Paediatrics and Child Health

Ofatumumab is a monoclonal antibody that reduces the level of B cells that alter the progression of relapsing multiple sclerosis. Originally approved by the Food and Drug Administration (FDA) in August 2020, this meta-analysis determines the outcomes of four randomized controlled trials (RCTs) for endline outcomes of Gadolinium-enhancing T1 lesions on MRI scans reported as Cohen's d and relapse rate reported as risk ratio. All four RCTs reported favorable findings of gadolinium-enhancing T1 lesions (Cohen's d = -0.44, p < 0.00001). The relapse rate was reduced by 46% post ofatumumab administration (RR = 0.54, p < 0.00001). With 14 ongoing trials in this area, more data is required to consolidate our findings.

Cerebellar Coordination Of Neuronal And Behavioral Rhythms, Brittany Correia Chapman

Theses and Dissertations (ETD)

Long known for its role in motor control, it is increasingly clear that the cerebellum is also involved in numerous cognitive and affective behaviors. Though the neuronal mechanism for the role of the cerebellum in cognition is still unclear, there is a consensus that it involves cerebellar interactions with the cerebral cortex. Recent studies suggest that the cerebellum monitors, and possibly coordinates, the precise phase alignment or coherence of neuronal oscillations in cerebral cortical areas. Here, we asked how loss of cerebellar function affects respiratory rhythms and the interactions of local field potential (LFP) oscillations between the lobulus simplex (LS) …

Spontaneous Pneumothorax: A Rare Complication Of Neurofibromatosis Type 1 Associated Diffuse Lung Disease, Emma I. Sherfinski, Mark H. Cooper Md, Phd

Marshall Journal of Medicine

The visually striking neurocutaneous findings of neurofibromatosis type 1 (NF1) are well recognized and have been well documented throughout scientific literature. While not uncommon, the pulmonary manifestations of NF1 are unknown to many physicians. Complications of NF1 associated diffuse lung disease (NF-DLD) include pulmonary hypertension, pulmonary artery stenosis, subpleural cysts, and spontaneous pneumothorax. We present a case of a 34-year-old male with NF-DLD found incidentally in adolescence with previous apical bleb repair, presenting nearly twenty years later with spontaneous pneumothorax. In NF1 patients with pulmonary complaints, NF-DLD should be assessed with computed tomography (CT) and physicians should be familiar with …

Efficacy And Safety Of A Brain-Penetrant Biologic Tnf-Α Inhibitor In Aged App/Ps1 Mice, Weijun Ou, Yuu Ohno, Joshua Yang, Devaraj V. Chandrashekar, Tamara Abdullah, Jiahong Sun, Riley Murphy, Chuli Roules, Nataraj Jagadeesan, David H. Cribbs, Rachita K. Sumbria

Pharmacy Faculty Articles and Research

Tumor necrosis factor alpha (TNF-α) plays a vital role in Alzheimer’s disease (AD) pathology, and TNF-α inhibitors (TNFIs) modulate AD pathology. We fused the TNF-α receptor (TNFR), a biologic TNFI that sequesters TNF-α, to a transferrin receptor antibody (TfRMAb) to deliver the TNFI into the brain across the blood–brain barrier (BBB). TfRMAb-TNFR was protective in 6-month-old transgenic APP/PS1 mice in our previous work. However, the effects and safety following delayed chronic TfRMAb-TNFR treatment are unknown. Herein, we initiated the treatment when the male APP/PS1 mice were 10.7 months old (delayed treatment). Mice were injected intraperitoneally with saline, TfRMAb-TNFR, etanercept (non-BBB-penetrating …

Plasma High-Density Lipoprotein Cargo Is Altered In Alzheimer's Disease And Is Associated With Regional Brain Volume, Steve Pedrini, James D. Doecke, Eugene Hone, Penghao Wang, Rohith Thota, Ashley I. Bush, Christopher C. Rowe, Vincent Dore, Victor L. Villemagne, David Ames, Stephanie Rainey-Smith, Giuseppe Verdile, Hamid R. Sohrabi, Manfred R. Raida, Kevin Taddei, Sam Gandy, Colin L. Masters, Pratishtha Chatterjee, Ralph N. Martins, Aibl Research Group

Research outputs 2022 to 2026

Cholesterol levels have been repeatedly linked to Alzheimer's Disease (AD), suggesting that high levels could be detrimental, but this effect is likely attributed to Low-Density Lipoprotein (LDL) cholesterol. On the other hand, High-Density Lipoproteins (HDL) cholesterol levels have been associated with reduced brain amyloidosis and improved cognitive function. However, recent findings have suggested that HDL-functionality, which depends upon the HDL-cargo proteins associated with HDL, rather than HDL levels, appears to be the key factor, suggesting a quality over quantity status. In this report, we have assessed the HDL-cargo (Cholesterol, ApoA-I, ApoA-II, ApoC-I, ApoC-III, ApoD, ApoE, ApoH, ApoJ, CRP, and SAA) …

Alzheimer's Disease, Dylan L. Weber

Student Publications

An overview of the background, etiology, pathophysiology, clinical features, diagnosis, treatment and prevention of Alzheimer's disease.

Heterozygous Variants In Myh10 Associated With Neurodevelopmental Disorders And Congenital Anomalies With Evidence For Primary Cilia-Dependent Defects In Hedgehog Signaling, Alexander M Holtz, Rachel Vancoillie, Elizabeth A Vansickle, Deanna Alexis Carere, Kara Withrow, Erin Torti, Jane Juusola, Francisca Millan, Richard Person, Maria J Guillen Sacoto, Yue Si, Ingrid M Wentzensen, Jada Pugh, Georgia Vasileiou, Melissa Rieger, André Reis, Emanuela Argilli, Elliott H Sherr, Kimberly A Aldinger, William B Dobyns, Theresa Brunet, Julia Hoefele, Matias Wagner, Benjamin Haber, Urania Kotzaeridou, Boris Keren, Delphine Heron, Cyril Mignot, Solveig Heide, Thomas Courtin, Julien Buratti, Serini Murugasen, Kirsten A Donald, Emily O'Heir, Shade Moody, Katherine H Kim, Barbara K Burton, Grace Yoon, Miguel Del Campo, Diane Masser-Frye, Mariya Kozenko, Christina Parkinson, Susan L Sell, Patricia L Gordon, Jeremy W Prokop, Amel Karaa, Caleb Bupp, Benjamin A Raby

Faculty, Staff and Student Publications

PURPOSE: Nonmuscle myosin II complexes are master regulators of actin dynamics that play essential roles during embryogenesis with vertebrates possessing 3 nonmuscle myosin II heavy chain genes, MYH9, MYH10, and MYH14. As opposed to MYH9 and MYH14, no recognizable disorder has been associated with MYH10. We sought to define the clinical characteristics and molecular mechanism of a novel autosomal dominant disorder related to MYH10.

METHODS: An international collaboration identified the patient cohort. CAS9-mediated knockout cell models were used to explore the mechanism of disease pathogenesis.

RESULTS: We identified a cohort of 16 individuals with heterozygous MYH10 variants presenting with a …

Modulation Of Hepatic Amyloid Precursor Protein And Lipoprotein Receptor-Related Protein 1 By Chronic Alcohol Intake: Potential Link Between Liver Steatosis And Amyloid-Β, Jerome Garcia, Rudy Chang, Ross A. Steinberg, Aldo Arce, Joshua Yang, Peter Van Der Eb, Tamara Abdullah, Devaraj V. Chandrashekar, Syndey M. Eck, Pablo Meza, Zhang-Xu Liu, Enrique Cadenas, David H. Cribbs, Neil Kaplowitz, Rachita K. Sumbria, Derick Han

Pharmacy Faculty Articles and Research

Heavy alcohol consumption is a known risk factor for various forms of dementia and the development of Alzheimer’s disease (AD). In this work, we investigated how intragastric alcohol feeding may alter the liver-to-brain axis to induce and/or promote AD pathology. Four weeks of intragastric alcohol feeding to mice, which causes significant fatty liver (steatosis) and liver injury, caused no changes in AD pathology markers in the brain [amyloid precursor protein (APP), presenilin], except for a decrease in microglial cell number in the cortex of the brain. Interestingly, the decline in microglial numbers correlated with serum alanine transaminase (ALT) levels, suggesting …