Medicine and Health Sciences Commons^™

Microglia In Post-Mortem Hippocampal Brain Tissue Of Male And Female Neonates After Hie, Kassandra M. Pulido, Angela N. Viaene, Amelia J. Eisch, Danielle G. Barber

Research Colloquium

Background: Hypoxic-ischemic encephalopathy (HIE) is the second-leading cause of neonatal morbidity and mortality worldwide. There are sex differences in the pathophysiology of HIE, particularly in microglia, which are critical in the immune response. Prior work highlights microglial aggregation in the hippocampus of human infants as a marker for HIE, but it is unknown whether this differs by sex.

Aim: We compare the microglial response in post-mortem hippocampal tissue from male and female neonates diagnosed with HIE vs. Controls who expired from other causes.

Methods: Using a retrospective cohort design, we reviewed medical records of neonates with hippocampal tissue in the …

In Vivo Examination Of Peripheral Drivers Of Alzheimer’S Disease, Celso Catumbela

Dissertations & Theses (Open Access)

Alzheimer’s disease (AD) is the leading cause of dementia worldwide, and predominantly affects elderly populations. This disease is well known for its effects on the brain, but a wealth of clinical reports show that dementia can also modify, or be modified by, various peripheral and systemic processes. Yet, the pathological contribution of peripheral comorbidities to AD remains to be fully understood. In an attempt to address some knowledge gaps, we characterized the cerebral and peripheral pathology in mice with history of either liver injury or sepsis. In the former subjects, we found that even in the absence of genetic risk …

Selective Targeting Of Microglia By Quantum Dots And Green Synthesis Of Metal Organic Biohybrids; Applications In Dynamic Cell And Assay Systems, Navya Uppu

Doctoral Dissertations

Neurological disorders are the leading cause of physical and cognitive disability across the globe, currently affecting approximately 15% of the worldwide population. Part of the glioma microenvironment are microglia, resident immune cells of the CNS that were thought to be involved in the pathogenesis of diverse neurodegenerative diseases. Though it remains uncertain what triggers microglial activation in these disorders, targeting and tracking microglial functions using nanotools like Quantum Dots (QDs) could help us elucidate them in such neurological diseases. This research focuses on the comparative study of different QDs formulations and their selective uptake by brain microglia in primary cultures …

In Sickness And In Health-Type I Interferon And The Brain, Wei Cao

Faculty and Staff Publications

Type I interferons (IFN-I) represent a group of pleiotropic cytokines renowned for their antiviral activity and immune regulatory functions. A multitude of studies have unveiled a critical role of IFN-I in the brain, influencing various neurological processes and diseases. In this mini-review, I highlight recent findings on IFN-I's effects on brain aging, Alzheimer's disease (AD) progression, and central nervous system (CNS) homeostasis. The multifaceted influence of IFN-I on brain health and disease sheds light on the complex interplay between immune responses and neurological processes. Of particular interest is the cGAS-STING-IFN-I axis, which extensively participates in brain aging and various forms …

Fornix Volumetric Increase During Aging Associates To Microglia Activation Leading To Defective Cognitive Performance, Marcela Cárdenas Tueme, Luis Ángel Trujillo-Villarreal, Victor Ramírez-Amaya, Eduardo Garza-Villarreal, Alberto Camacho-Morales, Diana Reséndez-Pérez

Research Symposium

Background: Ageing displays a low-grade pro-inflammatory profile in blood and brain. It has been documented proinflammatory cytokines accumulation leading to neuroinflammation during aging. Aged brains integrate pro inflammatory cytokines accumulation, active microglia and volumetric changes which correlates with defective cognitive performance and neurodegeneration.

Methods: Mice from 2-,12- and 20-months-old of age were submitted to different memory tests: Y-maze, Barnes maze, object location test and object location test. Afterwards, we performed structural MRI to evaluate macrostructural changes related to memory and learning regions. Following this, we also evaluated in peripheral blood and in brain tissue the presence of pro-inflammatory cytokines …

Pet Imaging Of Microglia Using Pbr28suv Determines Therapeutic Efficacy Of Autologous Bone Marrow Mononuclear Cells Therapy In Traumatic Brain Injury, Supinder S Bedi, Michael C Scott, Max A Skibber, Akshita Kumar, Henry W Caplan, Hasen Xue, David Sequeira, Alison L Speer, Fanni Cardenas, Franciska Gudenkauf, Karen Uray, Amit K Srivastava, Alan R Prossin, Charles S Cox

Student and Faculty Publications

Traumatic brain injury (TBI) results in activated microglia. Activated microglia can be measured in vivo by using positron emission topography (PET) ligand peripheral benzodiazepine receptor standardized uptake values (PBR28suv). Cell based therapies have utilized autologous bone marrow mononuclear cells (BMMNCs) to attenuate activated microglia after TBI. This study aims to utilize in vivo PBR28suv to assess the efficacy of BMMNCs therapy after TBI. Seventy-two hours after CCI injury, BMMNCs were harvested from the tibia and injected via tail-vein at 74 h after injury at a concentration of 2 million cells per kilogram of body weight. There were three groups of …

Csf1r Regulates Schizophrenia-Related Stress Response And Vascular Association Of Microglia/Macrophages, Ling Yan, Yanli Li, Fengmei Fan, Mengzhuang Gou, Fangling Xuan, Wei Feng, Keerthana Chithanathan, Wei Li, Junchao Huang, Hongna Li, Wenjin Chen, Baopeng Tian, Zhiren Wang, Shuping Tan, Alexander Zharkovsky, L Elliot Hong, Yunlong Tan, Li Tian

Student and Faculty Publications

BACKGROUND: Microglia are known to regulate stress and anxiety in both humans and animal models. Psychosocial stress is the most common risk factor for the development of schizophrenia. However, how microglia/brain macrophages contribute to schizophrenia is not well established. We hypothesized that effector molecules expressed in microglia/macrophages were involved in schizophrenia via regulating stress susceptibility.

METHODS: We recruited a cohort of first episode schizophrenia (FES) patients (n = 51) and age- and sex-paired healthy controls (HCs) (n = 46) with evaluated stress perception. We performed blood RNA-sequencing (RNA-seq) and brain magnetic resonance imaging, and measured plasma level of colony stimulating …

Bystanders Or Not? Microglia And Lymphocytes In Aging And Stroke, Justin N Nguyen, Anjali Chauhan

Student and Faculty Publications

As the average age of the world population increases, more people will face debilitating aging-associated conditions, including dementia and stroke. Not only does the incidence of these conditions increase with age, but the recovery afterward is often worse in older patients. Researchers and health professionals must unveil and understand the factors behind age-associated diseases to develop a therapy for older patients. Aging causes profound changes in the immune system including the activation of microglia in the brain. Activated microglia promote T lymphocyte transmigration leading to an increase in neuroinflammation, white matter damage, and cognitive impairment in both older humans and …

The Effects Of Exosomal Derived Tsg-6 On Microglia Activation, Jonathan A. Martinez, Rajashekhar Gangaraju Md

Longitudinal Scholar's Project

Following a traumatic brain injury, microglia become overactive for long periods and display pathologic behavior. We have shown that concentrated conditioned media from adipose tissue-derived mesenchymal stem cells (MSC-CCM) can suppress microglial activation. In this pilot study, we evaluated the efficacy of exosomes containing TNF-stimulated gene 6 (TSG6) derived from MSC-CCM on decreasing microglial activation in vitro via phagocytic activity and pro-inflammatory microglial gene expression.

Bioinformatic Analysis Predicts Microglial Dysfunction In Murine Aging, Amadu Idrisa Jalloh

USF Tampa Graduate Theses and Dissertations

Age-related disease is a growing concern as the global geriatric population increases. Neurodegenerative diseases scale unfavorably in prevalence with aging and inflict disastrous consequences to human health and well-being. These disorders are challenging to investigate because they arise from complex molecular origins. The neuroimmune system is a common factor among these diseases and microglia play an important role in maintaining homeostasis in the central nervous system. Aging progressively impairs microglia by decreasing their ability to adapt and respond to noxious environmental stimuli or injury. Microglial dysfunction aggravates neurodegenerative pathology when microglia are unable to regulate neuroinflammation effectively. We investigated aging …

Intravital Imaging Of Cellular Response Due To Traumatic Brain Injury Using Confocal Microscopy, Enoch G. Kim, Jeffrey Horbatiuk, Carolyn Harris

Medical Student Research Symposium

Introduction: Cellular reaction to traumatic brain injury is complex and involves considerable interactions between cells and reactivity to foreign bodies. Our objective was to assess neurons, microglia, astrocytes, and intracellular Ca²⁺ signaling by creating a novel confocal microscopy technique involving an air immersed lens that does not sacrifice resolution and limits signal attenuation. This study aimed to create a consistent dynamic methodology to observe the cortical cellular response using real-time intravital imaging as trauma is being induced.

Methods: Once surgical plane was achieved, rodent cortices were exposed via craniotomy and blunt insertion with a silicone shunt catheter into the …

Massive Loss Of Proprioceptive Ia Synapses In Rat Spinal Motoneurons After Nerve Crush Injuries In The Postnatal Period, Ariadna Arbat-Plana, Sara Bolívar, Xavier Navarro, Esther Udina, Francisco J. Alvarez

Neuroscience, Cell Biology & Physiology Faculty Publications

Peripheral nerve injuries (PNIs) induce the retraction from the ventral horn of the synaptic collaterals of Ia afferents injured in the nerve, effectively removing Ia synapses from α-motoneurons. The loss of Ia input impairs functional recovery and could explain, in part, better recovery after PNIs with better Ia synaptic preservation. Synaptic losses correlate with injury severity, speed, and efficiency of muscle reinnervation and requires ventral microglia activation. It is unknown whether this plasticity is age dependent. In neonates, axotomized motoneurons and sensory neurons undergo apoptosis, but after postnatal day 10 most survive. The goal of this study was to analyze …

Trogocytosis Of Neurons And Glial Cells By Microglia In A Healthy Adult Macaque Retina, Megan Goyal, Andrea S Bordt, Jay Neitz, David W Marshak

Student and Faculty Publications

Microglial cells are the primary resident immune cells in the retina. In healthy adults, they are ramified; that is, they have extensive processes that move continually. In adult retinas, microglia maintain the normal structure and function of neurons and other glial cells, but the mechanism underlying this process is not well-understood. In the mouse hippocampus, microglia engulf small pieces of axons and presynaptic terminals via a process called trogocytosis. Here we report that microglia in the adult macaque retina also engulf pieces of neurons and glial cells, but not at sites of synapses. We analyzed microglia in a volume of …

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

Graduate Theses, Dissertations, and Problem Reports

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 …

Role Of Adenylyl Cyclase Type 7 In Functions Of Bv-2 Microglia, Yawen Hu, Rebecca A. Hill, Masami Yoshimura

School of Medicine Faculty Publications

To assess the role of adenylyl cyclase type 7 (AC7) in microglia’s immune function, we generated AC7 gene knockout (AC7 KO) clones from a mouse microglial cell line, BV-2, using the CRISPR-Cas9 gene editing system. The ability of BV-2 cells to generate cAMP and their innate immune functions were examined in the presence or absence of ethanol. The parental BV-2 cells showed robust cAMP production when stimulated with prostaglandin-E1 (PGE1) and ethanol increased cAMP production in a dose-dependent manner. AC7 KO clones of BV-2 cells showed diminished and ethanol-insensitive cAMP production. The phagocytic activity of the parental BV-2 cells was …

Genetic Expression Changes And Pathologic Findings Associated With Hyperhomocysteinemia In Human Autopsy Brain Tissue, Erica M. Weekman, Zachary Winder, Colin B. Rogers, Erin L. Abner, Tiffany L. Sudduth, Ela Patel, Adam J. Dugan, Shuling X. Fister, Brandi Wasek, Peter T. Nelson, Gregory A. Jicha, Teodoro Bottiglieri, David W. Fardo, Donna M. Wilcock

Sanders-Brown Center on Aging Faculty Publications

Introduction: Vascular contributions to cognitive impairment and dementia (VCID) are a leading cause of dementia. An underappreciated, modifiable risk factor for VCID is hyperhomocysteinemia (HHcy), defined by elevated levels of plasma homocysteine, most often due to impaired B vitamin absorption in aged persons. Studies aimed at identifying neuropathologic features and gene expression profiles associated with HHcy have been lacking.

Methods: A subset of research volunteers from the University of Kentucky Alzheimer’s Disease Research Center longitudinal cohort came to autopsy and had ante mortem plasma homocysteine levels available. Brain tissue and blood plasma drawn closest to death were used to measure …

Mesenchymal Stromal Cells For The Treatment Of Alzheimer’S Disease: Strategies And Limitations, Shobha Regmi, Daniel Dan Liu, Michelle Shen, Bhavesh D Kevadiya, Abantika Ganguly, Rosita Primavera, Shashank Chetty, Reza Yarani, Avnesh S Thakor

Student and Faculty Publications

Alzheimer's disease (AD) is a major cause of age-related dementia and is characterized by progressive brain damage that gradually destroys memory and the ability to learn, which ultimately leads to the decline of a patient's ability to perform daily activities. Although some of the pharmacological treatments of AD are available for symptomatic relief, they are not able to limit the progression of AD and have several side effects. Mesenchymal stem/stromal cells (MSCs) could be a potential therapeutic option for treating AD due to their immunomodulatory, anti-inflammatory, regenerative, antioxidant, anti-apoptotic, and neuroprotective effects. MSCs not only secret neuroprotective and anti-inflammatory factors …

The Role Of Microglia In Neuroinflammation Of The Spinal Cord After Peripheral Nerve Injury, Tana S. Pottorf, Travis M. Rotterman, William M. Mccallum, Zoë A. Haley-Johnson, Francisco J. Alvarez

Neuroscience, Cell Biology & Physiology Faculty Publications

Peripheral nerve injuries induce a pronounced immune reaction within the spinal cord, largely governed by microglia activation in both the dorsal and ventral horns. The mechanisms of activation and response of microglia are diverse depending on the location within the spinal cord, type, severity, and proximity of injury, as well as the age and species of the organism. Thanks to recent advancements in neuro-immune research techniques, such as single-cell transcriptomics, novel genetic mouse models, and live imaging, a vast amount of literature has come to light regarding the mechanisms of microglial activation and alluding to the function …

Hdac6 Inhibition Reverses Long-Term Doxorubicin-Induced Cognitive Dysfunction By Restoring Microglia Homeostasis, Blake Mcalpin

Dissertations & Theses (Open Access)

One in 8 women in the US will be diagnosed with breast cancer. Currently, doxorubicin is one of the most effective chemotherapies for breast cancer. Unfortunately, up to 60% of survivors report long-term chemotherapy-induced cognitive dysfunction (CICD) characterized by deficits in working memory, processing speed, and executive functioning. Currently, no interventions for CICD have been approved by the US Food and Drug Administration. I show here that a 14-day treatment with a blood-brain barrier permeable histone deacetylase 6 (HDAC6) inhibitor successfully reverses long-term CICD following a therapeutic doxorubicin dosing schedule in female mice, as assessed by the puzzle box test …

Ameliorative Effects Of Minor Cannabinoids Over Hiv-1 Tat-Mediated Visceral Pain, Charlie Worth

Honors Theses

As the total number of people living with HIV continues to rise across the world, an effective HIV treatment is still sought after. While modern-day advanced therapies exist for mitigating much of the negative effects of HIV, the virus remains evasive and problematic in the central nervous system. Thus, even with treatment, many people living with HIV continue to suffer from a plethora of symptoms. However, a large proportion of HIV-positive patients claim to feel a reduction in those persevering symptoms after cannabis usage. This anecdotal evidence has sparked interest in the efficacy of cannabis constituents for HIV therapy. This …

Gm1 Ganglioside Modifies Microglial And Neuroinflammatory Responses To Α-Synuclein In The Rat Aav-A53t Α-Synuclein Model Of Parkinson's Disease, Jay S Schneider, Garima Singh, Courtney K. Williams, Vikrant Singh

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Among the pathological events associated with the dopaminergic neurodegeneration characteristic of Parkinson's disease (PD) are the accumulation of toxic forms of α-synuclein and microglial activation associated with neuroinflammation. Although numerous other processes may participate in the pathogenesis of PD, the two factors mentioned above may play critical roles in the initiation and progression of dopamine neuron degeneration in PD. In this study, we employed a slowly progressing model of PD using adeno-associated virus-mediated expression of human A53T α-synuclein into the substantia nigra on one side of the brain and examined the microglial response in the striatum on the injected side …

Immunomodulatory Roles Of The Lysosomal Sialidase Neuraminidase 1, Leigh Ellen Fremuth

Theses and Dissertations (ETD)

Background Sialic acids are key sugar moieties located at the non-reducing terminals of glycan chains on glycoproteins and glycolipids. By virtue of their location, they influence the functions and biochemical properties of the macromolecules they are bound to. Removal of sialic acids in mammalian cells is carried out by four sialidases, which are differentially expressed and localized in distinct subcellular compartments. Neuraminidase 1 (NEU1), the most abundant and ubiquitous of the four sialidases, functions primarily in the acidic environment of the lysosomes, but can hydrolyze substrates at the plasma membrane, at least in certain cell types. The enzyme initiates the …

Rotenone Induces Regionally Distinct Α-Synuclein Protein Aggregation And Activation Of Glia Prior To Loss Of Dopaminergic Neurons In C57bl/6 Mice, Savannah M Rocha, Collin M Bantle, Tawfik Aboellail, Debotri Chatterjee, Richard Jay Smeyne, Ronald B Tjalkens

Department of Neuroscience Faculty Papers

Rotenone is a naturally occurring insecticide that inhibits mitochondrial complex I and leads to neurochemical and neuropathological deficits closely resembling those in Parkinson's disease (PD). Deficits include loss of dopaminergic neurons (DAn) in the substantia nigra pars compacta (SNpc), decreased dopamine levels and aggregation of misfolded alpha-synuclein (p129). In rat models of rotenone-induced parkinsonism, the progression of neuronal injury has been associated with activation of microglia and astrocytes. However, these neuroinflammatory changes have been challenging to study in mice, in part because the systemic rotenone exposure model utilized in rats is more toxic to mice. To establish a reproducible murine …

The Anti-Inflammatory Agent Bindarit Attenuates The Impairment Of Neural Development Through Suppression Of Microglial Activation In A Neonatal Hydrocephalus Mouse Model, Eri Iwasawa, Farrah N. Brown, Crystal Shula, Fatima Kahn, Sang Hoon Lee, Temugin Berta, David R. Ladle, Kenneth Campbell, Francesco T. Mangano, June Goto

Neuroscience, Cell Biology & Physiology Faculty Publications

Neonatal hydrocephalus presents with various degrees of neuroinflammation and long-term neurologic deficits in surgically treated patients, provoking a need for additional medical treatment. We previously reported elevated neuroinflammation and severe periventricular white matter damage in the progressive hydrocephalus (prh) mutant which contains a point mutation in the Ccdc39 gene, causing loss of cilia-mediated unidirectional CSF flow. In this study, we identified cortical neuropil maturation defects such as impaired excitatory synapse maturation and loss of homeostatic microglia, and swimming locomotor defects in early postnatal prh mutant mice. Strikingly, systemic application of the anti-inflammatory small molecule bindarit significantly supports healthy …

Microglial Iron Trafficking: New Player In Brain Injury, Elif Keles, Hasan Hüseyi̇n Kazan, Lati̇fe Arzu Aral, Hayrunni̇sa Bolay Belen

Turkish Journal of Medical Sciences

Neonatal brain injury is a significant reason of neurodevelopmental abnormalities and long-term neurological impairments. Hypoxic-ischemic encephalopathy and preterm brain injury, including intraventricular hemorrhage are the most common grounds of brain injury for full-term and preterm neonates. The prevalence of hypoxic ischemic encephalopathy varies globally, ranging from 1 to 3.5/1000 live births in high-resource countries and 26/1000 in low-resource countries. Preterm birth's global incidence is 15 million, a significant reason for infant mortality and morbidity, permanent neurologic problems, and the associated social and economic burden. The widespread neurodevelopmental effects of neonatal brain injury could have an unfavorable impact on a variety …

The Prospect Of Nanoparticle Systems For Modulating Immune Cell Polarization During Central Nervous System Infection, Lee E. Korshoj, Wen Shi, Bin Duan, Tammy Kielian

Journal Articles: Pathology and Microbiology

The blood-brain barrier (BBB) selectively restricts the entry of molecules from peripheral circulation into the central nervous system (CNS) parenchyma. Despite this protective barrier, bacteria and other pathogens can still invade the CNS, often as a consequence of immune deficiencies or complications following neurosurgical procedures. These infections are difficult to treat since many bacteria, such as Staphylococcus aureus, encode a repertoire of virulence factors, can acquire antibiotic resistance, and form biofilm. Additionally, pathogens can leverage virulence factor production to polarize host immune cells towards an anti-inflammatory phenotype, leading to chronic infection. The difficulty of pathogen clearance is magnified by …

Myeloid Arginase 1 Insufficiency Exacerbates Amyloid-Β Associated Neurodegenerative Pathways And Glial Signatures In A Mouse Model Of Alzheimer’S Disease: A Targeted Transcriptome Analysis, Chao Ma, Jerry B. Hunt, Andrii Kovalenko, Huimin Liang, Maj-Linda B. Selenica, Michael B. Orr, Bei Zhang, John C. Gensel, David J. Feola, Marcia N. Gordon, Dave Morgan, Paula C. Bickford, Daniel C. Lee

Sanders-Brown Center on Aging Faculty Publications

Brain myeloid cells, include infiltrating macrophages and resident microglia, play an essential role in responding to and inducing neurodegenerative diseases, such as Alzheimer’s disease (AD). Genome-wide association studies (GWAS) implicate many AD casual and risk genes enriched in brain myeloid cells. Coordinated arginine metabolism through arginase 1 (Arg1) is critical for brain myeloid cells to perform biological functions, whereas dysregulated arginine metabolism disrupts them. Altered arginine metabolism is proposed as a new biomarker pathway for AD. We previously reported Arg1 deficiency in myeloid biased cells using lysozyme M (LysM) promoter-driven deletion worsened amyloidosis-related neuropathology and behavioral impairment. However, …

Interactions Of Neuroimmune Signaling And Glutamate Plasticity In Addiction, Cassandra D. Gipson, Scott Rawls, Michael D. Scofield, Benjamin M. Siemsen, Emma O. Bondy, Erin E. Maher

Family and Community Medicine Faculty Publications

Chronic use of drugs of abuse affects neuroimmune signaling; however, there are still many open questions regarding the interactions between neuroimmune mechanisms and substance use disorders (SUDs). Further, chronic use of drugs of abuse can induce glutamatergic changes in the brain, but the relationship between the glutamate system and neuroimmune signaling in addiction is not well understood. Therefore, the purpose of this review is to bring into focus the role of neuroimmune signaling and its interactions with the glutamate system following chronic drug use, and how this may guide pharmacotherapeutic treatment strategies for SUDs. In this review, we first describe …

CertL Reduces C16 Ceramide, Amyloid-Β Levels, And Inflammation In A Model Of Alzheimer’S Disease, Simone M. Crivelli, Qian Luo, Jo A. A. Stevens, Caterina Giovagnoni, Daan Van Kruining, Gerard Bode, Sandra Den Hoedt, Barbara Hobo, Anna-Lena Scheithauer, Jochen Walter, Monique T. Mulder, Christopher Exley, Matthew Mold, Michelle M. Mielke, Helga E. De Vries, Kristiaan Wouters, Daniel L. A. Van Den Hove, Dusan Berkes, María Dolores Ledesma, Joost Verhaagen, Mario Losen, Erhard Bieberich, Pilar Martinez-Martinez

Physiology Faculty Publications

BACKGROUND: Dysregulation of ceramide and sphingomyelin levels have been suggested to contribute to the pathogenesis of Alzheimer's disease (AD). Ceramide transfer proteins (CERTs) are ceramide carriers which are crucial for ceramide and sphingomyelin balance in cells. Extracellular forms of CERTs co-localize with amyloid-β (Aβ) plaques in AD brains. To date, the significance of these observations for the pathophysiology of AD remains uncertain.

METHODS: A plasmid expressing CERT_L, the long isoform of CERTs, was used to study the interaction of CERT_L with amyloid precursor protein (APP) by co-immunoprecipitation and immunofluorescence in HEK cells. The recombinant CERT_L protein …

Arginase 1 Insufficiency Precipitates Amyloid-Β Deposition And Hastens Behavioral Impairment In A Mouse Model Of Amyloidosis, Chao Ma, Jerry B. Hunt, Maj-Linda B. Selenica, Awa Sanneh, Leslie A. Sandusky-Beltran, Mallory Watler, Rana Daas, Andrii Kovalenko, Huimin Liang, Devon Placides, Chuanhai Cao, Xiaoyang Lin, Michael B. Orr, Bei Zhang, John C. Gensel, David J. Feola, Marcia N. Gordon, Dave Morgan, Paula C. Bickford, Daniel C. Lee

Sanders-Brown Center on Aging Faculty Publications

Alzheimer’s disease (AD) includes several hallmarks comprised of amyloid-β (Aβ) deposition, tau neuropathology, inflammation, and memory impairment. Brain metabolism becomes uncoupled due to aging and other AD risk factors, which ultimately lead to impaired protein clearance and aggregation. Increasing evidence indicates a role of arginine metabolism in AD, where arginases are key enzymes in neurons and glia capable of depleting arginine and producing ornithine and polyamines. However, currently, it remains unknown if the reduction of arginase 1 (Arg1) in myeloid cell impacts amyloidosis. Herein, we produced haploinsufficiency of Arg1 by the hemizygous deletion in myeloid cells using Arg1 …