ijms-logo

Journal Browser

Journal Browser

Special Issue "Microglia Heterogeneity and Its Relevance for Translational Research"

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: 30 September 2021.

Special Issue Editors

Dr. Alessandro Michelucci
E-Mail Website
Guest Editor
Neuro-Immunology Group, Department of Oncology, Luxembourg Institute of Health, Luxembourg, Luxembourg
Interests: neuroinflammation; glial cells; myeloid cells; microglia; brain tumours; immuno-oncology; neurodegeneration; immunometabolism
Prof. Dr. Josef Priller
E-Mail Website1 Website2
Guest Editor
Department of Neuropsychiatry and Laboratory of Molecular Psychiatry, Charité—Universitätsmedizin Berlin, Berlin, Germany
Interests: microglia; myeloid cells; neuroinflammation; neurodegeneration; neuropsychiatry; regenerative medicine; stem cells
Dr. Veronique Miron
E-Mail Website
Guest Editor
MRC Center for Reproductive Health, The Queen's Medical Research Institute, The University of Edinburgh, Edinburgh, United Kingdom
Interests: microglia; myeloid cells; neuroinflammation; remyelination; myelination; regenerative medicine; stem cells; oligodendrocyte

Special Issue Information

Dear Colleagues,

Microglia are essential for the development and function of the adult brain. Their ontogeny, together with the singular environment of the central nervous system (CNS), make microglia a rather unique population of immune effector cells. The exceptional properties of microglial cells during development, as well as in the adult CNS, such as their role in synaptic stripping or the remarkable capacity to scan the brain parenchyma and rapidly react to its perturbations, have emerged in the past. More recently, technological advances in molecular biology, imaging, and single-cell analyses have further provided fascinating insights into the dynamic changes and diversity of microglia in response to aging and brain diseases, revealing their potential as therapeutic targets.

This Special Issue aims to provide a comprehensive overview of our current understanding of the diversity of microglia spanning from brain regional heterogeneity under homeostasis to disease-associated microglia emerging with distinct transcriptional profiles reflecting specific activation states under pathological settings, including tumorigenic and degenerative processes. Thus, we welcome the submission of articles that cover, but are not limited to the role of microglia in inflammatory processes associated with brain diseases as well as strategies for patient stratification, diagnostics or treatment of CNS disorders based on dynamic molecular changes in microglia.


Dr. Alessandro Michelucci
Prof. Dr. Josef Priller
Dr. Veronique Miron
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 papers will be 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
  • Heterogeneity
  • Neuroinflammation
  • Neurodegeneration
  • Brain tumours
  • Translational medicine
  • Immunotherapy
  • Precision medicine

Published Papers (4 papers)

Order results
Result details
Select all
Export citation of selected articles as:

Research

Jump to: Review

Open AccessArticle
Microglial Heterogeneity and Its Potential Role in Driving Phenotypic Diversity of Alzheimer’s Disease
Int. J. Mol. Sci. 2021, 22(5), 2780; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22052780 - 09 Mar 2021
Viewed by 608
Abstract
Alzheimer’s disease (AD) is increasingly recognized as a highly heterogeneous disorder occurring under distinct clinical and neuropathological phenotypes. Despite the molecular determinants of such variability not being well defined yet, microglial cells may play a key role in this process by releasing distinct [...] Read more.
Alzheimer’s disease (AD) is increasingly recognized as a highly heterogeneous disorder occurring under distinct clinical and neuropathological phenotypes. Despite the molecular determinants of such variability not being well defined yet, microglial cells may play a key role in this process by releasing distinct pro- and/or anti-inflammatory cytokines, potentially affecting the expression of the disease. We carried out a neuropathological and biochemical analysis on a series of AD brain samples, gathering evidence about the heterogeneous involvement of microglia in AD. The neuropathological studies showed differences concerning morphology, density and distribution of microglial cells among AD brains. Biochemical investigations showed increased brain levels of IL-4, IL-6, IL-13, CCL17, MMP-7 and CXCL13 in AD in comparison with control subjects. The molecular profiling achieved by measuring the brain levels of 25 inflammatory factors known to be involved in neuroinflammation allowed a stratification of the AD patients in three distinct “neuroinflammatory clusters”. These findings strengthen the relevance of neuroinflammation in AD pathogenesis suggesting, in particular, that the differential involvement of neuroinflammatory molecules released by microglial cells during the development of the disease may contribute to modulate the characteristics and the severity of the neuropathological changes, driving—at least in part—the AD phenotypic diversity. Full article
(This article belongs to the Special Issue Microglia Heterogeneity and Its Relevance for Translational Research)
Show Figures

Graphical abstract

Open AccessArticle
Underestimated Peripheral Effects Following Pharmacological and Conditional Genetic Microglial Depletion
Int. J. Mol. Sci. 2020, 21(22), 8603; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21228603 - 15 Nov 2020
Cited by 4 | Viewed by 1073
Abstract
Microglia, predominant parenchymal resident macrophages in the central nervous system (CNS), are crucial players in neurodevelopment and CNS homeostasis. In disease conditions, pro-inflammatory microglia predominate over their regulatory counterparts, and are thus a potential immunotherapeutic target. It has been well documented that microglia [...] Read more.
Microglia, predominant parenchymal resident macrophages in the central nervous system (CNS), are crucial players in neurodevelopment and CNS homeostasis. In disease conditions, pro-inflammatory microglia predominate over their regulatory counterparts, and are thus a potential immunotherapeutic target. It has been well documented that microglia can be effectively depleted using both conditional genetic Cx3cr1Cre-diphtheria toxin receptor (DTR)/diphtheria toxin subunit A (DTA) animal models and pharmacological colony-stimulating factor 1 receptor (CSF1R) inhibitors. Recent advances using these approaches have expanded our knowledge of the multitude of tasks conducted by microglia in both homeostasis and diseases. Importantly, experimental microglial depletion has been proven to exert neuroprotective effects in an increasing number of disease models, mostly explained by reduced neuroinflammation. However, the comprehensive effects of additional targets such as circulating monocytes and peripheral tissue macrophages during microglial depletion periods have not been investigated widely, and for those studies addressing the issue the conclusions are mixed. In this study, we demonstrate that experimental microglial depletion using both Cx3cr1CreER/+Rosa26DTA/+ mice and different doses of CSF1R inhibitor PLX3397 exert crucial influences on circulating monocytes and peripheral tissue macrophages. Our results suggest that effects on peripheral immunity should be considered both in interpretation of microglial depletion studies, and especially in the potential translation of microglial depletion and replacement therapies. Full article
(This article belongs to the Special Issue Microglia Heterogeneity and Its Relevance for Translational Research)
Show Figures

Figure 1

Review

Jump to: Research

Open AccessReview
The Contribution of Microglia to Neuroinflammation in Parkinson’s Disease
Int. J. Mol. Sci. 2021, 22(9), 4676; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22094676 - 28 Apr 2021
Viewed by 391
Abstract
With the world’s population ageing, the incidence of Parkinson’s disease (PD) is on the rise. In recent years, inflammatory processes have emerged as prominent contributors to the pathology of PD. There is great evidence that microglia have a significant neuroprotective role, and that [...] Read more.
With the world’s population ageing, the incidence of Parkinson’s disease (PD) is on the rise. In recent years, inflammatory processes have emerged as prominent contributors to the pathology of PD. There is great evidence that microglia have a significant neuroprotective role, and that impaired and over activated microglial phenotypes are present in brains of PD patients. Thereby, PD progression is potentially driven by a vicious cycle between dying neurons and microglia through the instigation of oxidative stress, mitophagy and autophagy dysfunctions, a-synuclein accumulation, and pro-inflammatory cytokine release. Hence, investigating the involvement of microglia is of great importance for future research and treatment of PD. The purpose of this review is to highlight recent findings concerning the microglia-neuronal interplay in PD with a focus on human postmortem immunohistochemistry and single-cell studies, their relation to animal and iPSC-derived models, newly emerging technologies, and the resulting potential of new anti-inflammatory therapies for PD. Full article
(This article belongs to the Special Issue Microglia Heterogeneity and Its Relevance for Translational Research)
Show Figures

Figure 1

Open AccessReview
Microglia Diversity in Healthy and Diseased Brain: Insights from Single-Cell Omics
Int. J. Mol. Sci. 2021, 22(6), 3027; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22063027 - 16 Mar 2021
Viewed by 482
Abstract
Microglia are the resident immune cells of the central nervous system (CNS) that have distinct ontogeny from other tissue macrophages and play a pivotal role in health and disease. Microglia rapidly react to the changes in their microenvironment. This plasticity is attributed to [...] Read more.
Microglia are the resident immune cells of the central nervous system (CNS) that have distinct ontogeny from other tissue macrophages and play a pivotal role in health and disease. Microglia rapidly react to the changes in their microenvironment. This plasticity is attributed to the ability of microglia to adapt a context-specific phenotype. Numerous gene expression profiling studies of immunosorted CNS immune cells did not permit a clear dissection of their phenotypes, particularly in diseases when peripheral cells of the immune system come to play. Only recent advances in single-cell technologies allowed studying microglia at high resolution and revealed a spectrum of discrete states both under homeostatic and pathological conditions. Single-cell technologies such as single-cell RNA sequencing (scRNA-seq) and mass cytometry (Cytometry by Time-Of-Flight, CyTOF) enabled determining entire transcriptomes or the simultaneous quantification of >30 cellular parameters of thousands of individual cells. Single-cell omics studies demonstrated the unforeseen heterogeneity of microglia and immune infiltrates in brain pathologies: neurodegenerative disorders, stroke, depression, and brain tumors. We summarize the findings from those studies and the current state of knowledge of functional diversity of microglia under physiological and pathological conditions. A precise definition of microglia functions and phenotypes may be essential to design future immune-modulating therapies. Full article
(This article belongs to the Special Issue Microglia Heterogeneity and Its Relevance for Translational Research)
Show Figures

Figure 1

Back to TopTop