scholarly journals Effects of ZIKV + IgG+ complex on murine microglial cells

2021 ◽  
Author(s):  
Giulia Pinzetta ◽  
Nicole Bernd Becker ◽  
Felipe Krimberg ◽  
Ângela Zanatta ◽  
Laura Siqueira ◽  
...  
Keyword(s):  
Mitochondrial Membrane ◽  
Microglial Activation ◽  
Ros Production ◽  
Transplacental Transmission ◽  
Igg Antibodies ◽  
Murine Microglia ◽  
The Central Nervous System ◽  
Complex Methods

Background: Infection by Zika virus (ZIKV) is associated with damage to the Central Nervous System, such as Congenital Zika Syndrome1 . Due to its transplacental transmission, ZIKV induces neuroinflammation and microglial activation, resulting in lesions that can compromise neurodevelopment2-4. The fetus protection can be provided by maternal antibodies. However, this protection is still controversial5 . In this context, it is necessary to elucidate the effects of ZIKV and the mechanisms involved. Objectives: The present work aim to evaluate the role of the ZIKV+IgG+ complex in murine microglia cells (BV2). Design and setting: BV2 were exposed for 24 or 72 hours, to ZIKV, ZIKA-IgG+ or ZIKV+IgG+ complex. Methods: Effects of exposure to treatments were evaluated by MTT, oxidation of DCFHDA (ROS production)6 and mitochondrial membrane potential (Δ∴ϑ), measured by JC-17 assay. Results: It was observed that ZIKV-IgG+ and the ZIKV+IgG+ complex are cytotoxic to microglia, impairing the viability of these cells, altering Δ∴ϑ and inducing the production of ROS, especially in long-term exposure8,9. Negative action mediated by these antibodies may be a result of oxidative stress and a intervention in the Δ∴ϑ. Conclusion: ZIKV-IgG+ antibodies are harmful to microglia and these mechanisms may be related to the potential for ZIKV neuroinflammation.

scholarly journals Deficiency of microglial Hv1 channel is associated with activation of autophagic pathway and ROS production in LPC-induced demyelination mouse model

2020 ◽  
Vol 17 (1) ◽  
Author(s):  
Man Chen ◽  
Lin-Lin Yang ◽  
Zi-Wei Hu ◽  
Chuan Qin ◽  
Luo-Qi Zhou ◽  
...  
Keyword(s):  
Western Blot ◽  
Microglial Activation ◽  
Spatial Learning And Memory ◽  
Ros Production ◽  
Immune Mediated ◽  
Microglial Phenotype ◽  
The Central Nervous System ◽  
Phenotypic Transformation ◽  
System Activation

Abstract Background Multiple sclerosis (MS) is an immune-mediated demyelinated disease of the central nervous system. Activation of microglia is involved in the pathogenesis of myelin loss. Objective This study is focused on the role of Hv1 in regulating demyelination and microglial activation through reactive oxygen species (ROS) production after lysophosphatidylcholine (LPC)-mediated demyelination. We also explored autophagy in this process. Methods A model of demyelination using two-point LPC injection into the corpus callosum was established. LFB staining, immunofluorescence, Western blot, and electron microscopy were used to study the severity of demyelination. Microglial phenotype and autophagy were detected by immunofluorescence and Western blot. Morris water maze was used to test spatial learning and memory ability. Results We have identified that LPC-mediated myelin damage was reduced by Hv1 deficiency. Furthermore, we found that ROS and autophagy of microglia increased in the demyelination region, which was also inhibited by Hv1 knockout. Conclusion These results suggested that microglial Hv1 deficiency ameliorates demyelination through inhibition of ROS-mediated autophagy and microglial phenotypic transformation.

Neurotrophins and Proneurotrophins: Focus on Synaptic Activity and Plasticity in the Brain

2017 ◽  
Vol 23 (6) ◽  
pp. 587-604 ◽  
Author(s):  
Julien Gibon ◽  
Philip A. Barker
Keyword(s):  
Long Term Potentiation ◽  
Synaptic Activity ◽  
Cellular Processes ◽  
Term Potentiation ◽  
Neurotrophin 3 ◽  
New Findings ◽  
The Central Nervous System ◽  
The Brain

Neurotrophins have been intensively studied and have multiple roles in the brain. Neurotrophins are first synthetized as proneurotrophins and then cleaved intracellularly and extracellularly. Increasing evidences demonstrate that proneurotrophins and mature neurotrophins exerts opposing role in the central nervous system. In the present review, we explore the role of nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin 3 (NT3), and neurotrophin 4 (NT4) and their respective proform in cellular processes related to learning and memory. We focused on their roles in synaptic activity and plasticity in the brain with an emphasis on long-term potentiation, long-term depression, and basal synaptic transmission in the hippocampus and the temporal lobe area. We also discuss new findings on the role of the Val66Met polymorphism on the BDNF propeptide on synaptic activity.

scholarly journals Multifactorial Etiology of Adolescent Nicotine Addiction: A Review of the Neurobiology of Nicotine Addiction and Its Implications for Smoking Cessation Pharmacotherapy

2021 ◽  
Vol 9 ◽  
Author(s):  
Supriya D. Mahajan ◽  
Gregory G. Homish ◽  
Amanda Quisenberry
Keyword(s):  
Smoking Cessation ◽  
Microglial Activation ◽  
Therapeutic Potential ◽  
Nicotine Addiction ◽  
Neural Adaptations ◽  
Nicotine Abuse ◽  
Neuro Inflammation ◽  
Withdrawal Effects

Nicotine is the primary pharmacologic component of tobacco, and its highly addictive nature is responsible for its widespread use and significant withdrawal effects that result in challenges to smoking cessation therapeutics. Nicotine addiction often begins in adolescence and this is at least partially attributed to the fact that adolescent brain is most susceptible to the neuro-inflammatory effects of nicotine. There is increasing evidence for the involvement of microglial cells, which are the brain's primary homeostatic sensor, in drug dependence and its associated behavioral manifestations particularly in the adolescent brain. A hallmark of neuro-inflammation is microglial activation and activation of microglia by nicotine during adolescent development, which may result in long-term addiction to nicotine. This non-systematic review examines multifactorial etiology of adolescent nicotine addiction, neurobiology of nicotine addiction and the potential mechanisms that underlie the effects of nicotine on inflammatory signaling in the microglia, understanding how nicotine affects the adolescent brain. We speculate, that modulating homeostatic balance in microglia, could have promising therapeutic potential in withdrawal, tolerance, and abstinence-related neural adaptations in nicotine addiction, in the adolescent brain. Further, we discuss nicotine addiction in the context of the sensitization-homeostasis model which provides a theoretical framework for addressing the potential role of microglial homeostasis in neural adaptations underlying nicotine abuse.

scholarly journals The role of Neuropilin-1 in COVID-19

2021 ◽  
Vol 17 (1) ◽  
pp. e1009153
Author(s):  
Bindu S. Mayi ◽  
Jillian A. Leibowitz ◽  
Arden T. Woods ◽  
Katherine A. Ammon ◽  
Alphonse E. Liu ◽  
...  
Keyword(s):  
Immune Function ◽  
Viral Entry ◽  
Axonal Guidance ◽  
Cell Surface Receptor ◽  
Neuropilin 1 ◽  
Surface Receptor ◽  
The Central Nervous System

Neuropilin-1 (NRP-1), a member of a family of signaling proteins, was shown to serve as an entry factor and potentiate SARS Coronavirus 2 (SARS-CoV-2) infectivity in vitro. This cell surface receptor with its disseminated expression is important in angiogenesis, tumor progression, viral entry, axonal guidance, and immune function. NRP-1 is implicated in several aspects of a SARS-CoV-2 infection including possible spread through the olfactory bulb and into the central nervous system and increased NRP-1 RNA expression in lungs of severe Coronavirus Disease 2019 (COVID-19). Up-regulation of NRP-1 protein in diabetic kidney cells hint at its importance in a population at risk of severe COVID-19. Involvement of NRP-1 in immune function is compelling, given the role of an exaggerated immune response in disease severity and deaths due to COVID-19. NRP-1 has been suggested to be an immune checkpoint of T cell memory. It is unknown whether involvement and up-regulation of NRP-1 in COVID-19 may translate into disease outcome and long-term consequences, including possible immune dysfunction. It is prudent to further research NRP-1 and its possibility of serving as a therapeutic target in SARS-CoV-2 infections. We anticipate that widespread expression, abundance in the respiratory and olfactory epithelium, and the functionalities of NRP-1 factor into the multiple systemic effects of COVID-19 and challenges we face in management of disease and potential long-term sequelae.

Trypanosoma cruzi: death phenotypes induced by ortho-naphthoquinone substrates of the aldo-keto reductase (TcAKR). Role of this enzyme in the mechanism of action of β-lapachone

Parasitology ◽  
2018 ◽  
Vol 145 (9) ◽  
pp. 1251-1259 ◽  
Author(s):  
Patricia Andrea Garavaglia ◽  
María Fernanda Rubio ◽  
Marc Laverrière ◽  
Laura Mónica Tasso ◽  
Laura Edith Fichera ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Trypanosoma Cruzi ◽  
Mitochondrial Membrane ◽  
Major Influence ◽  
Ros Production ◽  
Oxygen Species ◽  
Aetiological Agent ◽  
Toxicity Evaluation

AbstractSeveral ortho-naphthoquinones (o-NQs) have trypanocidal activity against Trypanosoma cruzi, the aetiological agent of Chagas disease. Previously, we demonstrated that the aldo-keto reductase from this parasite (TcAKR) reduces o-NQs, such as β-lapachone (β-Lap) and 9,10-phenanthrenequinone (9,10-PQ), with concomitant reactive oxygen species (ROS) production. Recent characterization of TcAKR activity and expression in two T. cruzi strains, CL Brener and Nicaragua, showed that TcAKR expression is 2.2-fold higher in CL Brener than in Nicaragua. Here, we studied the trypanocidal effect and induction of several death phenotypes by β-Lap and 9,10-PQ in epimastigotes of these two strains. The CL Brener strain was more resistant to both o-NQs than Nicaragua, indicating that greater TcAKR activity is unlikely to be a major influence on o-NQ toxicity. Evaluation of changes in ROS production, mitochondrial membrane potential, phosphatidylserine exposure and monodansylcadaverine labelling evidenced that β-Lap and 9,10-PQ induce different death phenotypes depending on the combination of drug and T. cruzi strain analysed. To study whether TcAKR participates in o-NQ activation in intact parasites, β-Lap and 9,10-PQ trypanocidal effect was next evaluated in TcAKR-overexpressing parasites. Only β-Lap was more effective and induced greater ROS production in TcAKR-overexpressing epimastigotes than in controls, suggesting that TcAKR may participate in β-Lap activation.

scholarly journals Cytomorphological and Cytochemical Identification of Microglia

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Subhajit Das Sarma ◽  
Koushik Chatterjee ◽  
Himadri Dinda ◽  
Dhriti Chatterjee ◽  
Jayasri Das Sarma
Keyword(s):  
Central Nervous System ◽  
Animal Model ◽  
Immune Cells ◽  
Microglial Activation ◽  
Neurological Diseases ◽  
Neuronal Dysfunction ◽  
Ultrastructural Studies ◽  
The Central Nervous System ◽  
Made In

Microglia is one of the major resident immune cells in the central nervous system and is considered to be the key cellular mediator of neuroinflammatory processes. Identification of different Microglial states of activation by morphologic means has been one of the major challenges in the field of neurobiology of diseases. Therefore, microglial biology demands techniques to identify differing stages of microglia in different neuroanatomic locations as well as understanding the role of Microglia in different Neurological diseases. This present study is aimed towards summarizing the literature and for understanding the progress made in different Cytomorphological and Cytochemical techniques of identifying Microglia. This study also review recently used Immunohistochemistry techniques, along with Ultrastructural studies determining different morphological features of resting to activated phagocytic Microglia in a viral induced experimental animal model of neuroinflammation. Results revealed that chronic Microglial activation is considered to be an important component of neuronal dysfunction, injury, and loss (and hence to disease progression). Thus, Microglial research with special emphasis on identification of different activation states of Microglia has gradually become significant.

scholarly journals Metabolic Reprogramming and Cell Adhesion in Acute Leukemia Adaptation to the CNS Niche

2021 ◽  
Vol 9 ◽  
Author(s):  
Nitesh D. Sharma ◽  
Esra’a Keewan ◽  
Ksenia Matlawska-Wasowska
Keyword(s):  
Cell Adhesion ◽  
Acute Leukemia ◽  
Poor Prognosis ◽  
Significant Risk ◽  
Leukemic Cell ◽  
Metabolic Reprogramming ◽  
Leukemic Cells ◽  
The Central Nervous System

Involvement of the Central Nervous System (CNS) in acute leukemia confers poor prognosis and lower overall survival. Existing CNS-directed therapies are associated with a significant risk of short- or long-term toxicities. Leukemic cells can metabolically adapt and survive in the microenvironment of the CNS. The supporting role of the CNS microenvironment in leukemia progression and dissemination has not received sufficient attention. Understanding the mechanism by which leukemic cells survive in the nutrient-poor and oxygen-deprived CNS microenvironment will lead to the development of more specific and less toxic therapies. Here, we review the current literature regarding the roles of metabolic reprogramming in leukemic cell adhesion and survival in the CNS.

scholarly journals Prevalence of IgG antibodies to SARS-CoV-2 in Wuhan – implications for the ability to produce long-lasting protective antibodies against SARS-CoV-2

2020 ◽  
Author(s):  
Tao Liu ◽  
Sanyun Wu ◽  
Huangheng Tao ◽  
Guang Zeng ◽  
Fuling Zhou ◽  
...  
Keyword(s):  
Healthcare Workers ◽  
Healthcare Providers ◽  
Significant Proportion ◽  
Development Program ◽  
Data Access ◽  
Igg Antibodies ◽  
Funding Sources ◽  
Protective Antibodies

AbstractBackgroundIt is to be determined whether people infected with SARS-CoV-2 will develop long-term immunity against SARS-CoV-2 and retain long-lasting protective antibodies after the infection is resolved. This study was to explore to explore the outcomes of IgG antibodies to SARS-CoV-2 in four groups of individuals in Wuhan, China.MethodsWe included the following four groups of individuals who received both COVID-19 IgM/IgG tests and RT-PCR tests for SARS-CoV-2 from February 29, 2020 to April 29, 2020: 1470 hospitalized patients with COVID-19 from Leishenshan Hospital, Zhongnan Hospital of Wuhan University, and Wuhan No. 7 Hospital, 3832 healthcare providers without COVID-19 diagnosis, 19555 general workers, and 1616 other patients to be admitted to the hospital (N=26473). COVID-19 patients who received IgM/IgG tests <21 days after symptom onset were excluded.ResultsIgG prevalence was 89.8% (95% CI 88.2-91.3%) in COVID-19 patients, 4.0% (95% CI 3.4-4.7%) in healthcare providers, 4.6 (95% CI 4.3-4.9 %) in general workers, and 1.0% in other patients (p all <0.001 for comparisons with COVID-19 patients). IgG prevalence increased significantly by age among healthcare workers and general workers. Prevalence of IgM antibodies to SARS-CoV-2 was 31.4% in COVID-19 patients, 1.5% in healthcare providers, 1.3% in general workers, and 0.2% in other patients.ConclusionsVery few healthcare providers had IgG antibodies to SARS-CoV-2, though a significant proportion of them had been infected with the virus. After SARS-CoV-2 infection, people are unlikely to produce long-lasting protective antibodies against this virus.Primary Funding SourcesPart of the study was supported by National Key Research and Development Program of China (2020YFC0845500). The content is solely the responsibility of the authors and does not necessarily represent the official views of the sponsors.Role of the Funder/SponsorThe sponsors had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript, and decision to submit the manuscript for publication.Data and code availability statementData and analyses codes are available from the corresponding authors on request. All request for raw and analyzed data and materials will be reviewed by the corresponding authors to verify whether the request is subject to any intellectual property or confidentiality obligations. Access will be granted after a signed data access agreement is attained.

Induction of prostaglandin E2 synthesis and microsomal prostaglandin E synthase–1 expression in murine microglia by glioma-derived soluble factors

2008 ◽  
Vol 108 (2) ◽  
pp. 311-319 ◽  
Author(s):  
Yoshiteru Nakano ◽  
Etsushi Kuroda ◽  
Tomohiro Kito ◽  
Satoshi Uematsu ◽  
Shizuo Akira ◽  
...  
Keyword(s):  
Glioma Cells ◽  
Peritoneal Macrophages ◽  
Prostaglandin E ◽  
Soluble Factors ◽  
Arachidonate Cascade ◽  
Cox Inhibitor ◽  
Murine Microglia ◽  
The Central Nervous System

Object Microglia are one of the members of monocyte/macrophage lineage in the central nervous system (CNS) and exist as ramified microglia in a normal resting state, but they are activated by various stimuli, such as tumors. Activated microglia induce immune responses in the CNS, but the precise functions of microglia in glioma microenvironments are not clear. It has been reported that glioma cells produce prostaglandin (PG)E2, which promotes the growth of tumor cells and possesses immunosuppressive activity. The authors previously reported that PGE2 production by peritoneal macrophages was enhanced by glioma-derived soluble factors, which induce an immunosuppressive state. In this study, they investigated PGE2 production by microglia treated with glioma cells and assessed the role of microglia in glioma microenvironments in the mouse. Methods Microglia and peritoneal macrophages were cultured in vitro with or without lipopolysaccharide, and tumor necrosis factor (TNF) and PGE2 in the culture supernatant were measured using L929 bioassay and enzyme immunoassay. The expression of mRNA was measured using reverse transcriptase polymerase chain reaction, and the protein expression was assayed with Western blotting. In some experiments glioma cells and conditioned glioma medium were added to the microglia cultures. Results Glioma cells studied in this report did not produce a significant amount of PGE2. However, the coculture of microglia with glioma cells or conditioned glioma medium led to the production of a large amount of PGE2. The enhancement of PGE2 production by microglia was more significant than that by peritoneal macrophages. The expression of cyclooxygenase (COX)–2 and particularly the expression of microsomal PGE synthase (mPGES)–1 (a terminal enzyme of the arachidonate cascade) in microglia were enhanced by conditioned glioma medium. The enhancement of mPGES-1 expression in microglia was more significant than that in peritoneal macrophages. The production of TNF was suppressed when culturing microglia with conditioned glioma medium, but this suppression was abrogated by the addition of a COX inhibitor (NS-398) and a PGE2 receptor (EP4) antagonist. Furthermore, TNF production was not suppressed in microglia from mPGES-1–deficient mice. Conclusions These results indicate that PGE2 production by microglia is enhanced by conditioned glioma medium, which induces an immunosuppressive state in the CNS. Therefore, the manipulation of microglia, from the standpoint of PGE2, provides investigators with an important strategy to induce an effective antiglioma immune response.

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