Microglia in Physiology and Disease

Wolf, Susanne; Boddeke, Hendrikus; Kettenmann, Helmut

doi:10.1146/annurev-physiol-022516-034406

Cited by 1,042 publications

(878 citation statements)

References 131 publications

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“…This shared functionality included microglia as the main cell type, extracellular matrix as the main cellular component, and immune response as the main biological process. Microglia, constituting 5%-12% of all cells in the mouse and human brain (Lawson et al 1990;Lyck et al 2009;Olah et al 2018) and primarily known for their role in immune response, have recently been implicated in multiple brain functions including the regulation of learning-related synapse formation, synaptic plasticity, and cognition (Parkhurst et al 2013;Hong et al 2016;Tay et al 2017) and are linked with neurodegenerative and psychiatric disorders (Wolf et al 2017). Furthermore, microglial cells were shown to have different transcriptional identities in different brain regions (Grabert et al 2016).…”

Section: Discussionmentioning

confidence: 99%

Human-specific features of spatial gene expression and regulation in eight brain regions

Efimova

et al. 2018

Genome Res.

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Molecular maps of the human brain alone do not inform us of the features unique to humans. Yet, the identification of these features is important for understanding both the evolution and nature of human cognition. Here, we approached this question by analyzing gene expression and H3K27ac chromatin modification data collected in eight brain regions of humans, chimpanzees, gorillas, a gibbon, and macaques. An analysis of spatial transcriptome trajectories across eight brain regions in four primate species revealed 1851 genes showing human-specific transcriptome differences in one or multiple brain regions, in contrast to 240 chimpanzee-specific differences. More than half of these human-specific differences represented elevated expression of genes enriched in neuronal and astrocytic markers in the human hippocampus, whereas the rest were enriched in microglial markers and displayed human-specific expression in several frontal cortical regions and the cerebellum. An analysis of the predicted regulatory interactions driving these differences revealed the role of transcription factors in species-specific transcriptome changes, and epigenetic modifications were linked to spatial expression differences conserved across species.

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Section: Discussionmentioning

confidence: 99%

Human-specific features of spatial gene expression and regulation in eight brain regions

Efimova

et al. 2018

Genome Res.

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“…As mononuclear phagocytes of the CNS, microglia play an important role in maintaining normal brain functions in both physiological and pathological conditions (Wolf et al, 2017). In CNS development, microglia regulate neurogenesis by phagocyting apoptotic newborn cells in the sub-granular zone (Sierra et al, 2010) and support neuronal survival by accumulating around axons and secreting trophic factors like IGF-1 (Ueno et al, 2013).…”

Section: Microglial Activation and Polarizationmentioning

confidence: 99%

Role of Atypical Chemokine Receptors in Microglial Activation and Polarization

Salvi

Sozio

Sozzani

et al. 2017

Front. Aging Neurosci.

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Inflammatory reactions occurring in the central nervous system (CNS), known as neuroinflammation, are key components of the pathogenic mechanisms underlying several neurological diseases. The chemokine system plays a crucial role in the recruitment and activation of immune and non-immune cells in the brain, as well as in the regulation of microglia phenotype and function. Chemokines belong to a heterogeneous family of chemotactic agonists that signal through the interaction with G protein-coupled receptors (GPCRs). Recently, a small subset of chemokine receptors, now identified as “atypical chemokine receptors” (ACKRs), has been described. These receptors lack classic GPCR signaling and chemotactic activity and are believed to limit inflammation through their ability to scavenge chemokines at the inflammatory sites. Recent studies have highlighted a role for ACKRs in neuroinflammation. However, in the CNS, the role of ACKRs seems to be more complex than the simple control of inflammation. For instance, CXCR7/ACKR3 was shown to control T cell trafficking through the regulation of CXCL12 internalization at CNS endothelial barriers. Furthermore, D6/ACKR2 KO mice were protected in a model of experimental autoimmune encephalomyelitis (EAE). D6/ACKR2 KO showed an abnormal accumulation of dendritic cells at the immunization and a subsequent impairment in T cell priming. Finally, CCRL2, an ACKR-related protein, was shown to play a role in the control of the resolution phase of EAE. Indeed, CCRL2 KO mice showed exacerbated, non-resolving disease with protracted inflammation and increased demyelination. This phenotype was associated with increased microglia and macrophage activation markers and imbalanced M1 vs. M2 polarization. This review will summarize the current knowledge on the role of the ACKRs in neuroinflammation with a particular attention to their role in microglial polarization and function.

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“…Due to this continuous active surveillance, it has been suggested that “resting” microglia may not actually be the most appropriate term [4]. Evidence for other important roles of microglia in the healthy adult brain aside from immune surveillance, such as modulating neuronal activity and removing cell debris and dysfunctional synapses, is also greatly expanding and is reviewed extensively elsewhere [5,6,7]. …”

Section: The Numerous Functions and Phenotypes Of Microgliamentioning

confidence: 99%

The Diverse Roles of Microglia in the Neurodegenerative Aspects of Central Nervous System (CNS) Autoimmunity

Thompson

Tsirka

2017

IJMS

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Autoimmune diseases of the central nervous system (CNS) involve inflammatory components and result in neurodegenerative processes. Microglia, the resident macrophages of the CNS, are the first responders after insults to the CNS and comprise a major link between the inflammation and neurodegeneration. Here, we will focus on the roles of microglia in two autoimmune diseases: the prevalent condition of multiple sclerosis (MS) and the much rarer Rasmussen’s encephalitis (RE). Although there is an abundance of evidence that microglia actively contribute to neuronal damage in pathological states such as MS and RE, there is also evidence of important reparative functions. As current research supports a more complex and diverse array of functions and phenotypes that microglia can assume, it is an especially interesting time to examine what is known about both the damaging and restorative roles that microglia can play in the inflammatory CNS setting. We will also discuss the pharmacological approaches to modulating microglia towards a more neuroprotective state.

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Microglia in Physiology and Disease

Cited by 1,042 publications

References 131 publications

Human-specific features of spatial gene expression and regulation in eight brain regions

Human-specific features of spatial gene expression and regulation in eight brain regions

Role of Atypical Chemokine Receptors in Microglial Activation and Polarization

The Diverse Roles of Microglia in the Neurodegenerative Aspects of Central Nervous System (CNS) Autoimmunity

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