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Neuroinflammation Levels Measured By Microglial Cell Activation, Emma G. Whitlock, Linda S. Yasui May 2024

Neuroinflammation Levels Measured By Microglial Cell Activation, Emma G. Whitlock, Linda S. Yasui

Honors Capstones

Neuroinflammation is an inflammatory response in the brain that can be caused by different stressors such as diseases and/or external factors such as traumatic brain injuries. It is important to note duration and intensity of neuroinflammation levels when determining the impacts of these stressors to the brain environment. During neuroinflammation, a type of immune cell that becomes activated in the brain is called microglial cells. Microglial cells play a role in progression of the pathophysiological effects from the brain stressor. Studying changes in microglial cell shape provides evidence of the degree of neuroinflammation in the brain. Researchers can quantify neuroinflammation …


Isolation Of Aged Mouse Primary Microglia As A Model System For Alzheimer’S Disease Research, Michael Landis May 2024

Isolation Of Aged Mouse Primary Microglia As A Model System For Alzheimer’S Disease Research, Michael Landis

Biology Honors Papers

Microglia and their role as the immune cells of the central nervous system are an emerging area of interest within Alzheimer’s research, particularly as they have shown in a benevolent and malevolent cellular context. Models of Alzheimer’s disease are very light in studying microglia, so in this study a model of microglia isolated from aged mice is established in order to study the phagocytic activity and protein expression of microglia in response to Amyloid Beta. The cells were isolated from aged mice and cultured before being used to confirm cellular identity, as well as to measure phagocytic activity. This study …


Effects Of Methamphetamine On Microglia Through Reactive Oxygen Species, Chase Seiter, Jordan Yorgason, Nathan Sheets, James Blood, Lydia Hawley, Erin Taylor, Eliza White, Hillary Wadsworth, Jason Hansen Mar 2024

Effects Of Methamphetamine On Microglia Through Reactive Oxygen Species, Chase Seiter, Jordan Yorgason, Nathan Sheets, James Blood, Lydia Hawley, Erin Taylor, Eliza White, Hillary Wadsworth, Jason Hansen

Library/Life Sciences Undergraduate Poster Competition 2024

▪ Dopamine release in the Nucleus Accumbens (NAc) underlies motivational behavior for methamphetamine (METH) reward.

▪ ATP is a chemoattractant to microglia and is METH on ATP release and clearance are unknown.

▪ Furthermore, METH is known to produce reactive dopamine terminal function, microglia morphology and METH interactions are unknown.


Cyclophosphamide And Epirubicin Induce Apoptotic Cell Death In Microglia Cells, Rafael De La Hoz-Camacho Sep 2023

Cyclophosphamide And Epirubicin Induce Apoptotic Cell Death In Microglia Cells, Rafael De La Hoz-Camacho

Research Symposium

Background. Chemotherapy Related Cognitive Impairment’s (CRCI), diminish patient’s quality life, being breast cancer (BC) patients the most affected. Microglia is described to play a major role in CRCI; hence, the aim of this research was to describe the cytotoxicity of cyclophosphamide (CTX) and Epirubicin (EPI), on microglia (SIM-A9), compared to BC cells (4T1).

Methods. We assessed cell viability (Resazurin) and cell death (AnnV), as well as nuclear damage with γ-H2AX, p53, p16 and cell cycle analysis (PI staining) by flow cytometry (FC). Furthermore, we evaluated ΔΨm (DIOC6), ROS (DCFDA) and NO (DAF-FM) production. Finally, caspase activation (TF2-VAD-FMK) and autophagy (CYTO-ID). …


Complement System In Multiple Sclerosis: Its Role In Disease Course And Potential As A Therapeutic Target, Michael R. Linzey Jun 2023

Complement System In Multiple Sclerosis: Its Role In Disease Course And Potential As A Therapeutic Target, Michael R. Linzey

Dartmouth College Ph.D Dissertations

Multiple sclerosis (MS) is a clinically heterogeneous neurological condition characterized by neuroinflammation and neurodegeneration. Relapsing-remitting MS, defined by inflammatory attacks, is the most common initial form of MS and there are currently 23 FDA-approved treatments for these patients. These therapies work primarily by reducing inflammation in the CNS; they do not work well in progressive disease. Therefore, an unmet medical need exists for effective therapeutic options to treat progressive MS (PMS).

In MS, intrathecal immunoglobulins synthesis (IIgS) correlates with disease progression. My goals for this dissertation were to establish the pathological role of IIgS and identify new potential therapeutic …


The Effects Of A Blood–Brain Barrier Penetrating Erythropoietin In A Mouse Model Of Tauopathy, Joshua Yang, Weijun Ou, Nataraj Jagadeesan, Juste Simanauskaite, Jiahong Sun, Demi M. Castellanos, David H. Cribbs, Rachita K. Sumbria Apr 2023

The Effects Of A Blood–Brain Barrier Penetrating Erythropoietin In A Mouse Model Of Tauopathy, Joshua Yang, Weijun Ou, Nataraj Jagadeesan, Juste Simanauskaite, Jiahong Sun, Demi M. Castellanos, David H. Cribbs, Rachita K. Sumbria

Pharmacy Faculty Articles and Research

Erythropoietin (EPO), a hematopoietic neurotrophin, is a potential therapeutic for Alzheimer’s disease (AD) but has limited blood–brain barrier (BBB) permeability. EPO fused to a chimeric transferrin receptor monoclonal antibody (cTfRMAb) enters the brain via TfR-mediated transcytosis across the BBB. We previously showed that cTfRMAb-EPO is protective in a mouse model of amyloidosis, but its effects on tauopathy are not known. Given that amyloid and tau pathology are characteristics of AD, the effects of cTfRMAb-EPO were studied in a tauopathy mouse model (PS19). Six-month-old PS19 mice were injected intraperitoneally with either saline (PS19-Saline; n = 9) or cTfRMAb-EPO (PS19-cTfRMAb-EPO, 10 mg/kg; …


Neuroimmune-Mediated Alteration Of Acute Alcohol Exposure In The Mesolimbic Dopamine System, William T. Harris, P. E. Williams, Scott C. Steffensen Jan 2023

Neuroimmune-Mediated Alteration Of Acute Alcohol Exposure In The Mesolimbic Dopamine System, William T. Harris, P. E. Williams, Scott C. Steffensen

Library/Life Sciences Undergraduate Poster Competition 2023

2nd place open house

Dopamine (DA) transmission is a key player in the rewarding aspects of ethanol (EtOH) as well as EtOH dependence.

The current dogma is that DA transmission is increased during acute EtOH exposure via the inhibition of ventral tegmental area (VTA) GABA neurons and that the excitation of VTA GABA neurons during withdrawal results in decreased DA transmission.

Much recent evidence indicates that neuroimmune interactions may mediate this process. •

Microglia, the major neuroimmune effector in the brain, may be a key mediator in this process by releasing cytokines following activation.

Macrophages, a major immune effector in …


Rewired Metabolism In Apoe4 Microglia: Implications For Inflammation And Neurodegeneration, Nicholas A. Devanney Jan 2023

Rewired Metabolism In Apoe4 Microglia: Implications For Inflammation And Neurodegeneration, Nicholas A. Devanney

Theses and Dissertations--Physiology

Among the earliest changes to occur in Alzheimer’s disease, metabolic dysfunction and chronic neuroinflammation are now known to be major driving forces in disease progression. The paradigm of ‘immunometabolism’ seeks to bridge these two facets, positing that metabolic transformations are indispensable in determining the response of immune cells, such as microglia – the brain’s resident immune population. Proinflammatory stimulation of microglia leads to a shift away from mitochondrial respiration towards a dramatic upregulation of the glycolysis pathway for energy production. This glycolytic burst provides microglia with a rapid supply of ATP, but comes at a cost, as utilizing glucose to …


The Role Of Dha In The Impact Of Trem2 On Microglia Activation And Alzheimer’S Disease, Michael A. Palmieri Iii Dec 2022

The Role Of Dha In The Impact Of Trem2 On Microglia Activation And Alzheimer’S Disease, Michael A. Palmieri Iii

Seton Hall University Dissertations and Theses (ETDs)

Alzheimer’s disease (AD) is a neurological disease that is associated with microglia activation. An important receptor involved in microglia activation is Triggering receptor expressed on myeloid cells 2 (TREM2). Recent studies suggest that docosahexaenoic acid (DHA) could reduce the neuroinflammation that is associated with microglia activation. We hypothesized that when DHA concentration was increased, TREM2 expression would decrease, microglia activity would be inhibited, and a resulting decrease in neuroinflammation would be observed. We examined peer-reviewed journal articles from 2017-2022 that investigated the relationship between TREM2 activation and severity of AD symptoms, the protective properties of DHA against AD, and the …


The Characterization Of Microglia In The Murine Dorsal Telencephalon In Development And Disease, Victoria Neckles Dec 2022

The Characterization Of Microglia In The Murine Dorsal Telencephalon In Development And Disease, Victoria Neckles

All Dissertations

Microglia are the primary immune cells of the central nervous system and contribute substantially to both development and maintenance of the brain. Negative alterations to microglia often result in detrimental outcomes and significant effort is being made to understand these powerful cells. The goal of this research is to characterize microglia in the developing and diseased murine dorsal telencephalon. In vivo cell labeling and confocal microscopy identified a transient cell type, amoeboid microglia cells (AMCs), that appear to contribute to the development of microglia. Moreover, the spatial distribution and morphological change of microglia was thoroughly characterized during postnatal development. The …


Serpin-Derived Novel Peptide For The Treatment Against Hiv-Induced Inflammation In The Central Nervous System, Yemmy Soler Jun 2022

Serpin-Derived Novel Peptide For The Treatment Against Hiv-Induced Inflammation In The Central Nervous System, Yemmy Soler

FIU Electronic Theses and Dissertations

In the brain, HIV predominantly infects microglia/macrophages and astrocytes to a lesser extent. These cells form virus reservoirs with low levels of infection that are very hard to eradicate. Even though the use of cART increases survival rate in HIV patients, the virus persists as a chronic condition. cART is not able to effectively cross the BBB, control HIV replication, or attenuate inflammation in brain reservoirs. Therefore, the virus still causes neuronal dysfunction, pain-related pathology, and ultimately HAND. In this study, we decided to test the hypothesis that a serpin-derived small peptide, SP16, can serve as an anti-viral, anti-inflammatory, pro-survival, …


Novel App Knock-In Mouse Model Shows Key Features Of Amyloid Pathology And Reveals Profound Metabolic Dysregulation Of Microglia., Dan Xia, Steve Lianoglou, Thomas Sandmann, Meredith Calvert, Jung H Suh, Elliot Thomsen, Jason Dugas, Michelle E Pizzo, Sarah L Devos, Timothy K Earr, Chia-Ching Lin, Sonnet Davis, Connie Ha, Amy Wing-Sze Leung, Hoang Nguyen, Roni Chau, Ernie Yulyaningsih, Isabel Lopez, Hilda Solanoy, Shababa T Masoud, Chun-Chi Liang, Karin Lin, Giuseppe Astarita, Nathalie Khoury, Joy Yu Zuchero, Robert G Thorne, Kevin Shen, Stephanie Miller, Jorge J Palop, Dylan Garceau, Michael Sasner, Jennifer D Whitesell, Julie A Harris, Selina Hummel, Johannes Gnörich, Karin Wind, Lea Kunze, Artem Zatcepin, Matthias Brendel, Michael Willem, Christian Haass, Daniel Barnett, Till S Zimmer, Anna G Orr, Kimberly Scearce-Levie, Joseph W Lewcock, Gilbert Di Paolo, Pascal E Sanchez Jun 2022

Novel App Knock-In Mouse Model Shows Key Features Of Amyloid Pathology And Reveals Profound Metabolic Dysregulation Of Microglia., Dan Xia, Steve Lianoglou, Thomas Sandmann, Meredith Calvert, Jung H Suh, Elliot Thomsen, Jason Dugas, Michelle E Pizzo, Sarah L Devos, Timothy K Earr, Chia-Ching Lin, Sonnet Davis, Connie Ha, Amy Wing-Sze Leung, Hoang Nguyen, Roni Chau, Ernie Yulyaningsih, Isabel Lopez, Hilda Solanoy, Shababa T Masoud, Chun-Chi Liang, Karin Lin, Giuseppe Astarita, Nathalie Khoury, Joy Yu Zuchero, Robert G Thorne, Kevin Shen, Stephanie Miller, Jorge J Palop, Dylan Garceau, Michael Sasner, Jennifer D Whitesell, Julie A Harris, Selina Hummel, Johannes Gnörich, Karin Wind, Lea Kunze, Artem Zatcepin, Matthias Brendel, Michael Willem, Christian Haass, Daniel Barnett, Till S Zimmer, Anna G Orr, Kimberly Scearce-Levie, Joseph W Lewcock, Gilbert Di Paolo, Pascal E Sanchez

Faculty Research 2022

BACKGROUND: Genetic mutations underlying familial Alzheimer's disease (AD) were identified decades ago, but the field is still in search of transformative therapies for patients. While mouse models based on overexpression of mutated transgenes have yielded key insights in mechanisms of disease, those models are subject to artifacts, including random genetic integration of the transgene, ectopic expression and non-physiological protein levels. The genetic engineering of novel mouse models using knock-in approaches addresses some of those limitations. With mounting evidence of the role played by microglia in AD, high-dimensional approaches to phenotype microglia in those models are critical to refine our understanding …


Sex-Specific Effects Of Chaperone And Glial Defenses On Experimental Lewy Body Disease, Tarun Bhatia May 2022

Sex-Specific Effects Of Chaperone And Glial Defenses On Experimental Lewy Body Disease, Tarun Bhatia

Electronic Theses and Dissertations

Lewy body disorders are a group of neurodegenerative conditions characterized by the pathological misfolding and aggregation of the abundant protein, α-synuclein. The most common Lewy body disorders are Parkinson’s disease and dementia with Lewy bodies. Apart from ageing, male sex is a major risk factor for Lewy body disorders, as men are at ~1.5-fold higher risk for these diseases than women. Yet, preclinical studies on Lewy body disorders rarely examine sex as a biological variable, and the mechanisms underlying sex-skewedness in disease risk remain undetermined.

Here, we developed a sex-stratified model of Lewy body disorders by exposing primary neurons harvested …


Investigating The Neuroprotective Effects Of Cannabinoids And Insulin-Like Growth Factors On Glia With Induced Inflammation, Caleb Bloodworth May 2022

Investigating The Neuroprotective Effects Of Cannabinoids And Insulin-Like Growth Factors On Glia With Induced Inflammation, Caleb Bloodworth

Honors Theses

Chronic inflammation is a driver of numerous neurodegenerative diseases that reduce quality of life for affected individuals. Non-psychoactive cannabinoids have begun to gain more interest in the world of anti-inflammatory medicine for chronically ill patients. Along with these cannabinoids, insulin-like growth factor-1 has been examined for its association with downregulation of inflammation. Our research aimed to investigate how neuroglia are affected by treatment with cannabinoids or IGF-1 in the face of inflammation from HIV-1 protein, Tat, or lipopolysaccharide (LPS). Preliminary studies in our laboratory showed that neither cannabinoids or IGF-1 treatment altered astrocyte morphology or overall astrocyte viability under baseline …


Hdac6 Inhibition Reverses Long-Term Doxorubicin-Induced Cognitive Dysfunction By Restoring Microglia Homeostasis, Blake Mcalpin May 2022

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 …


Innate Lymphoid Cell Characterization And Ilc2s In Neuroinflammation In Aging And Sex Differences, Alexis Mobley, Alexis S. Mobley May 2022

Innate Lymphoid Cell Characterization And Ilc2s In Neuroinflammation In Aging And Sex Differences, Alexis Mobley, Alexis S. Mobley

Dissertations & Theses (Open Access)

Aging affects immunologic responses by a global immune system suppression, including dysregulation of cytokine mediators, leading to increased inflammation throughout all systems, termed inflammaging. However, understanding healthy aging mechanisms can bypass this effect. Inflammaging also leads to poor outcomes during brain injury, making immune-targeting therapeutics tantamount to overall brain health and longevity. Moreover, sex affects disease etiology and severity through hormonal and chromosomal sex, as the X chromosome contains most immunology-based genes. Androgens have a generally suppressive effect on the immune system. Additionally, when immune responses are mounted, males are better at CD4+ T cell type (Th1) responses, while females …


Emerging Roles For The Orphan Gpcrs, Gpr37 And Gpr37 L1, In Stroke Pathophysiology, Sabra Mouhi, Breona Martin, Sharon Owino Apr 2022

Emerging Roles For The Orphan Gpcrs, Gpr37 And Gpr37 L1, In Stroke Pathophysiology, Sabra Mouhi, Breona Martin, Sharon Owino

Neuroscience: Faculty Publications

Recent studies have shed light on the diverse and complex roles of G-protein coupled receptors (GPCRs) in the pathophysiology of stroke. These receptors constitute a large family of seven transmembrane-spanning proteins that play an intricate role in cellular communication mechanisms which drive both tissue injury and repair following ischemic stroke. Orphan GPCRs represent a unique sub-class of GPCRs for which no natural ligands have been found. Interestingly, the majority of these receptors are expressed within the central nervous system where they represent a largely untapped resource for the treatment of neurological diseases. The focus of this review will thus be …


Sex Differences In Myelin Deficits And Neuroinflammatory Responses To Adolescent Drinking In Rats, Andrea Silva-Gotay Mar 2022

Sex Differences In Myelin Deficits And Neuroinflammatory Responses To Adolescent Drinking In Rats, Andrea Silva-Gotay

Doctoral Dissertations

Alcohol binge drinking during adolescence is associated with higher risk of developing alcohol use disorders later in life. Alcohol can lead to decreased white matter volume, myelin damage, and neuroinflammation in animal models of adolescent binge alcohol exposure. These deficits in turn are associated with cognitive disfunctions that are long-lasting and could contribute to alcohol abuse and alcoholism later in life. Importantly, human males are more likely to develop alcohol use disorders than females, thus the mechanisms underlying this might be different between the sexes. Understanding how alcohol impacts the developing adolescent brain can help us identify molecular and cellular …


Conventional Therapies Deplete Brain-Infiltrating Adaptive Immune Cells In A Mouse Model Of Group 3 Medulloblastoma Implicating Myeloid Cells As Favorable Immunotherapy Targets, Zahra Abbas, Courtney George, Mathew Ancliffe, Meegan Howlett, Anya C. Jones, Mani Kuchibhotla, Robert J. Wechsler-Reya, Nicholas G. Gottardo, Raelene Endersby Mar 2022

Conventional Therapies Deplete Brain-Infiltrating Adaptive Immune Cells In A Mouse Model Of Group 3 Medulloblastoma Implicating Myeloid Cells As Favorable Immunotherapy Targets, Zahra Abbas, Courtney George, Mathew Ancliffe, Meegan Howlett, Anya C. Jones, Mani Kuchibhotla, Robert J. Wechsler-Reya, Nicholas G. Gottardo, Raelene Endersby

Research outputs 2022 to 2026

Medulloblastoma is the most common childhood brain cancer. Mainstay treatments of radiation and chemotherapy have not changed in decades and new treatment approaches are crucial for the improvement of clinical outcomes. To date, immunotherapies for medulloblastoma have been unsuccessful, and studies investigating the immune microenvironment of the disease and the impact of current therapies are limited. Preclinical models that recapitulate both the disease and immune environment are essential for understanding immune-tumor interactions and to aid the identification of new and effective immunotherapies. Using an immune-competent mouse model of aggressive Myc-driven medulloblastoma, we characterized the brain immune microenvironment and changes induced …


Epigallocatechin-3-Gallate (Egcg): New Therapeutic Perspectives For Neuroprotection, Aging, And Neuroinflammation For The Modern Age, Ashley Payne, Samuel N. Nahashon, Equar Taka, Getinet M. Adinew, Karam F. A. Soliman Feb 2022

Epigallocatechin-3-Gallate (Egcg): New Therapeutic Perspectives For Neuroprotection, Aging, And Neuroinflammation For The Modern Age, Ashley Payne, Samuel N. Nahashon, Equar Taka, Getinet M. Adinew, Karam F. A. Soliman

Agricultural and Environmental Sciences Faculty Research

Alzheimer's and Parkinson’s diseases are the two most common forms of neurodegenerative diseases. The exact etiology of these disorders is not well known; however, environmental, molecular, and genetic influences play a major role in the pathogenesis of these diseases. Using Alzheimer’s disease (AD) as the archetype, the pathological findings include the aggregation of Amyloid Beta (Aβ) peptides, mitochondrial dysfunction, synaptic degradation caused by inflammation, elevated reactive oxygen species (ROS), and cerebrovascular dysregulation. This review highlights the neuroinflammatory and neuroprotective role of epigallocatechin-3-gallate (EGCG): the medicinal component of green tea, a known nutraceutical that has shown promise in modulating AD progression …


Application Of Confocal Microscopy To Study The Neural Mechanisms Underlying Insect And Rodent Behavior, Christian Michelle Harris Jan 2022

Application Of Confocal Microscopy To Study The Neural Mechanisms Underlying Insect And Rodent Behavior, Christian Michelle Harris

Theses, Dissertations and Capstones

Posture and walking require support of the body weight, which is thought to be detected by sensory receptors in the legs. Specificity in sensory encoding occurs through the morphological properties of the sense organs (numerical distribution, receptor size) and their physiological response characteristics. These studies focus upon campaniform sensilla, receptors that detect forces as strains in the insect exoskeleton. To study the morphology of campaniform sensilla, the sites of mechanotransduction (cuticular caps) were imaged by light and confocal microscopy in four species (stick insects, cockroaches, blow flies and Drosophila). These data indicate that the gradient (range) of cap sizes may …


Microglia Polarize In Response To Transactive Response Dna-Binding Protein-43 (Tdp-43) And Display Partial Recovery After Removal Of The Stimulus, Alicen Wilcox Sep 2021

Microglia Polarize In Response To Transactive Response Dna-Binding Protein-43 (Tdp-43) And Display Partial Recovery After Removal Of The Stimulus, Alicen Wilcox

Honors Theses

The proper response to protein signals is necessary for a healthy central nervous system (CNS), and protein dysregulation is a feature of neurodegenerative diseases. Transactive response DNA-binding protein-43 (TDP-43) is an intranuclear protein, but mislocalization is associated with amyotrophic lateral sclerosis (ALS). TDP-43 is released into the extracellular space where it is sensed by microglia, the CNS-resident immune cells. Our data and the literature suggest that microglia respond to TDP-43 dysregulation by increasing CNS inflammation. The goal of this study was to determine the impact of TDP-43 on microglial function and the extent to which microglia recovery. To study the …


The Functional And Structural Consequences Of Aberrant Microglial Activity In Major Depressive Disorder, Jasmine D. Cakmak Sep 2021

The Functional And Structural Consequences Of Aberrant Microglial Activity In Major Depressive Disorder, Jasmine D. Cakmak

Electronic Thesis and Dissertation Repository

Major depressive disorder (MDD) is a highly debilitating neuropsychiatric illness which has been linked with increases in both peripheral and central inflammation, as well as with changes in connectivity. Although countless studies have investigated these two topics, the relationship between neuroinflammation and functional/structural connectivity has not been explored. Using [18F]FEPPA PET imaging, we measured translocator protein-related (TSPO) microglial activity in the subgenual anterior cingulate cortex (sgACC) and insula and confirmed significantly increased [18F]FEPPA uptake in depressed patients (N=12) compared to healthy controls (N=23). Using a seed-based ROI analysis of fMRI data, we found that patients show …


Human Microglia Extensively Reconstitute In Humanized-Blt Mice With Human Interleukin-34 Transgene And Support Hiv-1 Brain Infection, Jianshui Zhang, Saroj Chandra Lohani, Yilun Cheng, Tao Wang, Lili Guo, Woong-Ki Kim, Santhi Gorantla, Qingsheng Li Sep 2021

Human Microglia Extensively Reconstitute In Humanized-Blt Mice With Human Interleukin-34 Transgene And Support Hiv-1 Brain Infection, Jianshui Zhang, Saroj Chandra Lohani, Yilun Cheng, Tao Wang, Lili Guo, Woong-Ki Kim, Santhi Gorantla, Qingsheng Li

School of Biological Sciences: Faculty Publications

Humanized bone marrow-liver-thymic (hu-BLT) mice develop a functional immune system in periphery, nevertheless, have a limited reconstitution of human myeloid cells, especially microglia, in CNS. Further, whether bone marrow derived hematopoietic stem and progenitor cells (HSPCs) can enter the brain and differentiate into microglia in adults remains controversial. To close these gaps, in this study we unambiguously demonstrated that human microglia in CNS were extensively reconstituted in adult NOG mice with human interleukin-34 transgene (hIL34 Tg) from circulating CD34+ HSPCs, nonetheless not in hu-BLT NOG mice, providing strong evidence that human CD34+ HSPCs can enter adult brain and differentiate into …


Alcohol As A Catalyst For Hiv-Associated Neuroinflammation And Tbi-Induced Iron Toxicity, Agnieszka Agas Aug 2021

Alcohol As A Catalyst For Hiv-Associated Neuroinflammation And Tbi-Induced Iron Toxicity, Agnieszka Agas

Dissertations

Alcohol has long been considered an exacerbator of diseases, disorders, and injuries as well as many of the accompanying symptoms. As an alternative approach, this dissertation explores alcohol as a catalyst for two different human disease conditions, human immunodeficiency virus (HIV)-associated neuroinflammation and traumatic brain injury (TBI)-induced iron toxicity. In HIV-1 infection, this dissertation presents a novel anti-viral drug, called Drug-S, for a possible inhibition and treatment of HIV-1 disease progression.

The first aim explores the influence of alcohol with HIV-associated neuroinflammation on macrophage migration across an in vitro model of the blood brain barrier. There is a gap in …


Andrographolide Attenuates Gut-Brain-Axis Associated Pathology In Gulf War Illness By Modulating Bacteriome-Virome Associated Inflammation And Microglia-Neuron Proinflammatory Crosstalk, Punnag Saha, Peter T. Skidmore, Larinda A. Holland, Ayan Mondal, Dipro Bose, Ratanesh K. Seth, Kimberly Sullivan, Patricia A. Janulewicz, Ronnie Horner, Nancy Klimas, Mitzi Nagarkatti, Prakash Nagarkatti, Efrem S. Lim, Saurabh Chatterjee Jul 2021

Andrographolide Attenuates Gut-Brain-Axis Associated Pathology In Gulf War Illness By Modulating Bacteriome-Virome Associated Inflammation And Microglia-Neuron Proinflammatory Crosstalk, Punnag Saha, Peter T. Skidmore, Larinda A. Holland, Ayan Mondal, Dipro Bose, Ratanesh K. Seth, Kimberly Sullivan, Patricia A. Janulewicz, Ronnie Horner, Nancy Klimas, Mitzi Nagarkatti, Prakash Nagarkatti, Efrem S. Lim, Saurabh Chatterjee

Faculty Publications

Gulf War Illness (GWI) is a chronic multi-symptomatic illness that is associated with fatigue, pain, cognitive deficits, and gastrointestinal disturbances and presents a significant challenge to treat in clinics. Our previous studies show a role of an altered Gut-Brain axis pathology in disease development and symptom persistence in GWI. The present study utilizes a mouse model of GWI to study the role of a labdane diterpenoid andrographolide (AG) to attenuate the Gut-Brain axis-linked pathology. Results showed that AG treatment in mice (100 mg/kg) via oral gavage restored bacteriome alterations, significantly increased probiotic bacteria , , and , the genera that …


Cognitive Changes Caused By Lps-Induced Neuroinflammation, Nancy De La Torre Feb 2021

Cognitive Changes Caused By Lps-Induced Neuroinflammation, Nancy De La Torre

Dissertations, Theses, and Capstone Projects

The brain performs cognitive processes finely orchestrated by timely precise action of neurons. Neurons functioning at their highest standard communicate with each other through perfectly functioning synapses. Microglia, as part of the immune system assist synaptic processing and have the ability to affect cognition. Indeed, microglia play a role in cognition. To investigate the link between microglia and cognition we utilized lipopolysaccharide (LPS) to pharmacologically activate microglia. LPS, normally present in the environment on the wall of Gram-negative bacteria is a pharmacological agent used to cause microglia activation in mice. LPS is a typical model to study changes induced by …


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 Jan 2021

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 …


Myelin, Cpla2, And Azithromycin: Modulation Of Macrophage Activation In Spinal Cord Injury Inflammation, Timothy J. Kopper Jan 2021

Myelin, Cpla2, And Azithromycin: Modulation Of Macrophage Activation In Spinal Cord Injury Inflammation, Timothy J. Kopper

Theses and Dissertations--Physiology

Spinal cord injury (SCI) produces a chronic inflammatory state primarily mediated by macrophages consisting of resident microglia and infiltrating monocytes. These chronically activated SCI macrophages adopt a pro-inflammatory, pathological state that continues to cause additional damage after the initial injury and inhibits recovery. While the roles of macrophages in SCI pathophysiology are well documented, the factors contributing to this maladaptive response are poorly understood. Here, we identify the detrimental effects of myelin debris on macrophage physiology and demonstrate a novel, activation state-dependent role for cytosolic phospholipase-A2 (cPLA2) in myelin- mediated potentiation of pro-inflammatory macrophage activation. Macrophage- mediated inflammatory …


Cellular Iron Storage And Trafficking Are Affected By Gtn Stimulation In Primary Glial And Meningeal Cell Culture, Lati̇fe Arzu Aral, Mehmet Ali̇ Ergün, Hayrunni̇sa Bolay Belen Jan 2021

Cellular Iron Storage And Trafficking Are Affected By Gtn Stimulation In Primary Glial And Meningeal Cell Culture, Lati̇fe Arzu Aral, Mehmet Ali̇ Ergün, Hayrunni̇sa Bolay Belen

Turkish Journal of Biology

A well-balanced intracellular iron trafficking in glial cells plays a role in homeostatic processes. Elevated intracellular iron triggers oxidative stress and cell damage in many neurological disorders, including migraine. This study aimed to investigate the effects of glyceryl trinitrate (GTN), on cellular iron homeostasis, matrixmetalloproteinase (MMP)-9, and calcitonin gene related peptide (CGRP) receptor (CRLR/CGRPR1) production in microglia, astrocyte, and meningeal cell cultures. Primary glial and meningeal cells in culture were exposed to GTN for 24 h. Messenger RNA expression was assessed using qPCR. Iron accumulation was visualized via modified Perl?s histochemistry. MMP-9 levels in cell culture supernatants were measured using …