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Microglial Function in the Central Nervous System II

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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Neurobiology".

Deadline for manuscript submissions: closed (31 August 2023) | Viewed by 6550

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Special Issue Editor

Dr. Bin Liu

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Guest Editor

Department of Pharmacodynamics, University of Florida, Gainesville, FL 32610, USA
Interests: microglia; astroglia; neurodegeneration; neuroprotection; environmental toxicants; substances of abuse

Special Issue Information

Dear Colleagues,

Since the first description by the Spanish neuroscientist Pio del Rio-Hortega more than one hundred years ago, our understanding of microglia has continued to advance. As the resident immune cells in the central nervous system, microglia play a pivotal role in the maintenance of its homeostasis and the defense against invading pathogens and foreign substances. Aberrant activation of microglia has been associated with the pathogenesis of a wide variety of neurological disorders including neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease. Research in the last few decades has rapidly advanced our understanding of microglia from the recognition of being either “pro-” or “anti-inflammatory” when activated, to the realization that microglia are highly dynamic cells that exhibit a wide and progressive spectrum of phenotypes under both physiological and pathological conditions. Distinct phenotypes may underlie their involvement in the normal development and maintenance of the central nervous system as well as the pathogenesis of various neurological disorders. Moreover, microglia exhibit both spatial phenotypic characteristics within different regions of the central nervous system and temporal phenotypic transformation in response to changes in their microenvironment, the presence of abnormal substances and during the pathogenesis of neurological disorders, as well as sex dimorphism. This Special Issue welcomes research work on the characterization of microglial phenotypic transformation in various model systems to help gain a more complete understanding of their highly dynamic and multifaceted role in both health and disease.

Dr. Bin Liu
Guest Editor

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.

Keywords

microglia
phenotypic transformation
microglia during development
microglia in CNS homeostasis
microglia in neurological disorders
microglia and environmental toxicants

Published Papers (3 papers)

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Research

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19 pages, 7986 KiB

Open AccessArticle

Neuroimmune Activation and Microglia Reactivity in Female Rats Following Alcohol Dependence

by Jennifer K. Melbourne, Jessica I. Wooden, Erika R. Carlson, Chinchusha Anasooya Shaji and Kimberly Nixon

Int. J. Mol. Sci. 2024, 25(3), 1603; https://doi.org/10.3390/ijms25031603 - 28 Jan 2024

Viewed by 771

Abstract

The rates of alcohol use disorder among women are growing, yet little is known about how the female brain is affected by alcohol. The neuroimmune system, and specifically microglia, have been implicated in mediating alcohol neurotoxicity, but most preclinical studies have focused on males. Further, few studies have considered changes to the microglial phenotype when examining the effects of ethanol on brain structure and function. Therefore, we quantified microglial reactivity in female rats using a binge model of alcohol dependence, assessed through morphological and phenotypic marker expression, coupled with regional cytokine levels. In a time- and region-dependent manner, alcohol altered the microglial number and morphology, including the soma and process area, and the overall complexity within the corticolimbic regions examined, but no significant increases in the proinflammatory markers MHCII or CD68 were observed. The majority of cytokine and growth factor levels examined were similarly unchanged. However, the expression of the proinflammatory cytokine TNFα was increased, and the anti-inflammatory IL-10, decreased. Thus, female rats showed subtle differences in neuroimmune reactivity compared to past work in males, consistent with reports of enhanced neuroimmune responses in females across the literature. These data suggest that specific neuroimmune reactions in females may impact their susceptibility to alcohol neurotoxicity and other neurodegenerative events with microglial contributions. Full article

(This article belongs to the Special Issue Microglial Function in the Central Nervous System II)

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16 pages, 2753 KiB

Open AccessCommunication

The Central Nervous System Source Modulates Microglia Function and Morphology In Vitro

by Andreia G. Pinho, Andreia Monteiro, Sara Fernandes, Nídia de Sousa, António J. Salgado, Nuno A. Silva and Susana Monteiro

Int. J. Mol. Sci. 2023, 24(9), 7685; https://doi.org/10.3390/ijms24097685 - 22 Apr 2023

Viewed by 1759

Abstract

The regional heterogeneity of microglia was first described a century ago by Pio del Rio Hortega. Currently, new information on microglia heterogeneity throughout central nervous system (CNS) regions is being revealed by high-throughput techniques. It remains unclear whether these spatial specificities translate into different microglial behaviors in vitro. We cultured microglia isolated from the cortex and spinal cord and analyzed the effect of the CNS spatial source on behavior in vitro by applying the same experimental protocol and culture conditions. We analyzed the microglial cell numbers, function, and morphology and found a distinctive in vitro phenotype. We found that microglia were present in higher numbers in the spinal-cord-derived glial cultures, presenting different expressions of inflammatory genes and a lower phagocytosis rate under basal conditions or after activation with LPS and IFN-γ. Morphologically, the cortical microglial cells were more complex and presented longer ramifications, which were also observed in vivo in CX3CR1^+/GFP transgenic reporter mice. Collectively, our data demonstrated that microglial behavior in vitro is defined according to specific spatial characteristics acquired by the tissue. Thus, our study highlights the importance of microglia as a source of CNS for in vitro studies. Full article

(This article belongs to the Special Issue Microglial Function in the Central Nervous System II)

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Review

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38 pages, 1233 KiB

Open AccessReview

The Pathological Activation of Microglia Is Modulated by Sexually Dimorphic Pathways

by Jennifer L. O'Connor and Jillian C. Nissen

Int. J. Mol. Sci. 2023, 24(5), 4739; https://doi.org/10.3390/ijms24054739 - 1 Mar 2023

Cited by 4 | Viewed by 3629

Abstract

Microglia are the primary immunocompetent cells of the central nervous system (CNS). Their ability to survey, assess and respond to perturbations in their local environment is critical in their role of maintaining CNS homeostasis in health and disease. Microglia also have the capability of functioning in a heterogeneous manner depending on the nature of their local cues, as they can become activated on a spectrum from pro-inflammatory neurotoxic responses to anti-inflammatory protective responses. This review seeks to define the developmental and environmental cues that support microglial polarization towards these phenotypes, as well as discuss sexually dimorphic factors that can influence this process. Further, we describe a variety of CNS disorders including autoimmune disease, infection, and cancer that demonstrate disparities in disease severity or diagnosis rates between males and females, and posit that microglial sexual dimorphism underlies these differences. Understanding the mechanism behind differential CNS disease outcomes between men and women is crucial in the development of more effective targeted therapies. Full article

(This article belongs to the Special Issue Microglial Function in the Central Nervous System II)

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