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Molecular, Cellular and Systemic Signature of Microglia 2.0

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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (28 February 2022) | Viewed by 8526

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Special Issue Editors

Prof. Dr. Markus Ritter

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Institute for Physiology and Pathophysiology, Paracelsus Medical University, Salzburg, Austria
Interests: microglial; cancer stem cell; chloride current
Special Issues, Collections and Topics in MDPI journals

Prof. Dr. Hubert H. Kerschbaum

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Department of Cell Biology, University of Salzburg, 5020 Salzburg, Austria
Interests: microglial; cancer stem cell; chloride current

Special Issue Information

Dear Colleagues,

How do microglia, the innate immune cells of the central nervous system, shape the structure and function of the central nervous system? What happens when the neural environment changes due to an injury or microbial neuroinvasion? How do microglia communicate with astrocytes and neurons? Since the state of microglia is vital for the health of neural cells, answers to these questions are indispensable for understanding the (patho)physiology of the brain.

The structural phenotype of microglia reflects their functional state. The ramified phenotype, surveilling its environment in the healthy brain, transforms upon rupture of capillaries or microbial neuroinvasion into an amoeboid phagocyte, boosting the clearance of cell debris. While pruning of a surplus of synapses by microglia is physiological in early development, it may become pathophysiological in the adult brain, thus driving neurodegeneration.

Experimental evidence strongly points to the involvement of microglia in a diversity of neural functions, including the development of the brain, learning, neuroinflammation, fighting neuroinvasive microbes, and neurodegeneration. Reviews and original research papers presented in this Special Issue will provide an overview of the current state-of-the-art microglia research from all biomedical fields.

Prof. Dr. Markus Ritter
Prof. Dr. Hubert H. Kerschbaum
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Related Special Issue

Molecular, Cellular and Systemic Signature of Microglia in International Journal of Molecular Sciences (16 articles)

Published Papers (3 papers)

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Research

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22 pages, 3553 KiB

Open AccessArticle

Inhibition of Autotaxin and Lysophosphatidic Acid Receptor 5 Attenuates Neuroinflammation in LPS-Activated BV-2 Microglia and a Mouse Endotoxemia Model

by Lisha Joshi, Ioanna Plastira, Eva Bernhart, Helga Reicher, Alexander Triebl, Harald C. Köfeler and Wolfgang Sattler

Int. J. Mol. Sci. 2021, 22(16), 8519; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22168519 - 07 Aug 2021

Cited by 13 | Viewed by 2828

Abstract

Increasing evidence suggests that systemic inflammation triggers a neuroinflammatory response that involves sustained microglia activation. This response has deleterious consequences on memory and learning capability in experimental animal models and in patients. However, the mechanisms connecting systemic inflammation and microglia activation remain poorly understood. Here, we identify the autotaxin (ATX)/lysophosphatidic acid (LPA)/LPA-receptor axis as a potential pharmacological target to modulate the LPS-mediated neuroinflammatory response in vitro (the murine BV-2 microglia cell line) and in vivo (C57BL/6J mice receiving a single i.p. LPS injection). In LPS-stimulated (20 ng/mL) BV-2 cells, we observed increased phosphorylation of transcription factors (STAT1, p65, and c-Jun) that are known to induce a proinflammatory microglia phenotype. LPS upregulated ATX, TLR4, and COX2 expression, amplified NO production, increased neurotoxicity of microglia conditioned medium, and augmented cyto-/chemokine concentrations in the cellular supernatants. PF8380 (a type I ATX inhibitor, used at 10 and 1 µM) and AS2717638 (an LPA5 antagonist, used at 1 and 0.1 µM) attenuated these proinflammatory responses, at non-toxic concentrations, in BV-2 cells. In vivo, we demonstrate accumulation of PF8380 in the mouse brain and an accompanying decrease in LPA concentrations. In vivo, co-injection of LPS (5 mg/kg body weight) and PF8380 (30 mg/kg body weight), or LPS/AS2717638 (10 mg/kg body weight), significantly attenuated LPS-induced iNOS, TNFα, IL-1β, IL-6, and CXCL2 mRNA expression in the mouse brain. On the protein level, PF8380 and AS2717638 significantly reduced TLR4, Iba1, GFAP and COX2 expression, as compared to LPS-only injected animals. In terms of the communication between systemic inflammation and neuroinflammation, both inhibitors significantly attenuated LPS-mediated systemic TNFα and IL-6 synthesis, while IL-1β was only reduced by PF8380. Inhibition of ATX and LPA5 may thus provide an opportunity to protect the brain from the toxic effects that are provoked by systemic endotoxemia. Full article

(This article belongs to the Special Issue Molecular, Cellular and Systemic Signature of Microglia 2.0)

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11 pages, 1725 KiB

Open AccessArticle

MAO-A Inhibition by Metaxalone Reverts IL-1β-Induced Inflammatory Phenotype in Microglial Cells

by Giovanni Pallio, Angela D’Ascola, Luigi Cardia, Federica Mannino, Alessandra Bitto, Letteria Minutoli, Giacomo Picciolo, Violetta Squadrito, Natasha Irrera, Francesco Squadrito and Domenica Altavilla

Int. J. Mol. Sci. 2021, 22(16), 8425; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22168425 - 05 Aug 2021

Cited by 6 | Viewed by 2386

Abstract

Experimental and clinical studies have suggested that several neurological disorders are associated with the occurrence of central nervous system neuroinflammation. Metaxalone is an FDA-approved muscle relaxant that has been reported to inhibit monoamine oxidase A (MAO-A). The aim of this study was to investigate whether metaxalone might exert antioxidant and anti-inflammatory effects in HMC3 microglial cells. An inflammatory phenotype was induced in HMC3 microglial cells through stimulation with interleukin-1β (IL-1β). Control cells and IL-1β-stimulated cells were subsequently treated with metaxalone (10, 20, and 40 µM) for six hours. IL-1β stimulated the release of the pro-inflammatory cytokines tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6), but reduced the anti-inflammatory cytokine interleukin-13 (IL-13). The upstream signal consisted of an increased priming of nuclear factor-kB (NF-kB), blunted peroxisome proliferator-activated receptor gamma (PPARγ), and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) expression. IL-1β also augmented MAO-A expression/activity and malondialdehyde levels and decreased Nrf2 mRNA expression and protein levels. Metaxalone decreased MAO-A activity and expression, reduced NF-kB, TNF-α, and IL-6, enhanced IL-13, and also increased PPARγ, PGC-1α, and Nrf2 expression. The present experimental study suggests that metaxalone has potential for the treatment of several neurological disorders associated with neuroinflammation. Full article

(This article belongs to the Special Issue Molecular, Cellular and Systemic Signature of Microglia 2.0)

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Review

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17 pages, 1492 KiB

Open AccessReview

Systematic Review on Tumor Microenvironment in Glial Neoplasm: From Understanding Pathogenesis to Future Therapeutic Perspectives

by Andrea Bianconi, Gelsomina Aruta, Francesca Rizzo, Luca Francesco Salvati, Pietro Zeppa, Diego Garbossa and Fabio Cofano

Int. J. Mol. Sci. 2022, 23(8), 4166; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23084166 - 09 Apr 2022

Cited by 15 | Viewed by 2344

Abstract

Despite the multidisciplinary management in the treatment of glioblastomas, the average survival of GBM patients is still 15 months. In recent years, molecular biomarkers have gained more and more importance both in the diagnosis and therapy of glial tumors. At the same time, it has become clear that non neoplastic cells, which constitute about 30% of glioma mass, dramatically influence tumor growth, spread, and recurrence. This is the main reason why, in recent years, scientific research has been focused on understanding the function and the composition of tumor microenvironment and its role in gliomagenesis and recurrence. The aim of this review is to summarize the most recent discovery about resident microglia, tumor-associated macrophages, lymphocytes, and the role of extracellular vesicles and their bijective interaction with glioma cells. Moreover, we reported the most recent updates about new therapeutic strategies targeting immune system receptors and soluble factors. Understanding how glioma cells interact with non-neoplastic cells in tumor microenvironment is an essential step to comprehend mechanisms at the base of disease progression and to find new therapeutic strategies for GBM patients. However, no significant results have yet been obtained in studies targeting single molecules/pathways; considering the complex microenvironment, it is likely that only by using multiple therapeutic agents acting on multiple molecular targets can significant results be achieved. Full article

(This article belongs to the Special Issue Molecular, Cellular and Systemic Signature of Microglia 2.0)

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