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Journal ArticleDOI

Microglia During Development and Aging

01 Sep 2013-Pharmacology & Therapeutics (Pharmacol Ther)-Vol. 139, Iss: 3, pp 313-326
TL;DR: Information is provided on the colonization of the brain by microglia, the expression of various pattern recognition receptors to regulate migration and phagocytosis, and the shift in related functions that occur in normal aging.
About: This article is published in Pharmacology & Therapeutics.The article was published on 2013-09-01 and is currently open access. It has received 370 citations till now. The article focuses on the topics: Neuroinflammation & Synaptic pruning.
Citations
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Journal Article
TL;DR: Schulz et al. as discussed by the authors investigated whether adult macrophages all share a common developmental origin and found that a population of yolk-sac-derived, tissue-resident macophages was able to develop and persist in adult mice in the absence of hematopoietic stem cells.
Abstract: Macrophage Development Rewritten Macrophages provide protection against a wide variety of infections and critically shape the inflammatory environment in many tissues. These cells come in many flavors, as determined by differences in gene expression, cell surface phenotype and specific function. Schulz et al. (p. 86, published online 22 March) investigated whether adult macrophages all share a common developmental origin. Immune cells, including most macrophages, are widely thought to arise from hematopoietic stem cells (HSCs), which require the transcription factor Myb for their development. Analysis of Myb-deficient mice revealed that a population of yolk-sac–derived, tissue-resident macrophages was able to develop and persist in adult mice in the absence of HSCs. Importantly, yolk sac–derived macrophages also contributed substantially to the tissue macrophage pool even when HSCs were present. In mice, a population of tissue-resident macrophages arises independently of bone marrow–derived stem cells. Macrophages and dendritic cells (DCs) are key components of cellular immunity and are thought to originate and renew from hematopoietic stem cells (HSCs). However, some macrophages develop in the embryo before the appearance of definitive HSCs. We thus reinvestigated macrophage development. We found that the transcription factor Myb was required for development of HSCs and all CD11bhigh monocytes and macrophages, but was dispensable for yolk sac (YS) macrophages and for the development of YS-derived F4/80bright macrophages in several tissues, such as liver Kupffer cells, epidermal Langerhans cells, and microglia—cell populations that all can persist in adult mice independently of HSCs. These results define a lineage of tissue macrophages that derive from the YS and are genetically distinct from HSC progeny.

1,673 citations

Journal ArticleDOI
TL;DR: The interrelationships between Neuroinflammation and amyloid and tau pathologies as well as the effect of neuroinflammation on the disease trajectory in AD are discussed, focusing on microglia as major players in neuro inflammation and how these cells could be modulated as a therapeutic strategy for AD.
Abstract: Alzheimer disease (AD) is the most common form of neurodegenerative disease, estimated to contribute 60–70% of all cases of dementia worldwide. According to the prevailing amyloid cascade hypothesis, amyloid-β (Aβ) deposition in the brain is the initiating event in AD, although evidence is accumulating that this hypothesis is insufficient to explain many aspects of AD pathogenesis. The discovery of increased levels of inflammatory markers in patients with AD and the identification of AD risk genes associated with innate immune functions suggest that neuroinflammation has a prominent role in the pathogenesis of AD. In this Review, we discuss the interrelationships between neuroinflammation and amyloid and tau pathologies as well as the effect of neuroinflammation on the disease trajectory in AD. We specifically focus on microglia as major players in neuroinflammation and discuss the spatial and temporal variations in microglial phenotypes that are observed under different conditions. We also consider how these cells could be modulated as a therapeutic strategy for AD. Accumulating evidence indicates important roles for microglial activation and neuroinflammation in Alzheimer disease (AD). Here, Leng and Edison describe the interplay between microglial activation and AD-related pathologies and discuss how microglial priming and activation might influence the trajectory of AD.

859 citations

Journal ArticleDOI
21 May 2014-Neuron
TL;DR: It is suggested that synaptic changes are central to the disease process, and that the march of neurofibrillary tangles through brain circuits appears to take advantage of recently described mechanisms of transsynaptic spread of pathological forms of tau.

852 citations


Cites background from "Microglia During Development and Ag..."

  • ...…refinement, where they appear to engulf and remove dendritic spines ‘‘marked’’ for removal by members of the classical complement cascade complement receptor 3 and C1q (Chu et al., 2010; Clarke and Barres, 2013; Harry, 2013; Paolicelli et al., 2011; Stephan et al., 2013; Tremblay et al., 2010)....

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Journal ArticleDOI
TL;DR: This review summarizes the main functional relationships between retinal glial cells and neurons, presenting a general picture of the retina recently modified based on experimental observations.

564 citations


Cites background from "Microglia During Development and Ag..."

  • ...In the CNS, microglia are distributed widely in the gray and white matter, and they present local singularities related to their function (Harry, 2013)....

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  • ...The brain and the retina suffer agerelated deterioration/degeneration (Harry, 2013), and to discover the importance of age in this process, which cannot be avoided or changed, it is paramount to unravel the influence of the other main aetiological elements (for example life-style and environmental factors) on the initiation and progression of neurodegeneration....

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  • ...Microglia colonise CNS structures during embryogenesis and in the early postnatal period until they reach their positions in the mature brain (Harry, 2013)....

    [...]

Journal ArticleDOI
TL;DR: Interventions targeting immune-related cellular and molecular pathways may benefit subsets of MDD patients with immune dysregulation and ongoing studies examining neuroimmune mechanisms that influence neuronal activity as well as synaptic plasticity are discussed.
Abstract: Data from clinical and preclinical studies indicate that immune dysregulation, specifically of inflammatory processes, is associated with symptoms of major depressive disorder (MDD). In particular, increased levels of circulating pro-inflammatory cytokines and concomitant activation of brain-resident microglia can lead to depressive behavioural symptoms. Repeated exposure to psychological stress has a profound impact on peripheral immune responses and perturbs the function of brain microglia, which may contribute to neurobiological changes underlying MDD. Here, we review these findings and discuss ongoing studies examining neuroimmune mechanisms that influence neuronal activity as well as synaptic plasticity. Interventions targeting immune-related cellular and molecular pathways may benefit subsets of MDD patients with immune dysregulation.

458 citations

References
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Journal ArticleDOI
24 Feb 2006-Cell
TL;DR: New insights into innate immunity are changing the way the way the authors think about pathogenesis and the treatment of infectious diseases, allergy, and autoimmunity.

10,685 citations

Journal ArticleDOI
TL;DR: This Review suggests a new grouping of macrophages based on three different homeostatic activities — host defence, wound healing and immune regulation, and proposes that similarly to primary colours, these three basic macrophage populations can blend into various other 'shades' of activation.
Abstract: Macrophages display remarkable plasticity and can change their physiology in response to environmental cues. These changes can give rise to different populations of cells with distinct functions. In this Review we suggest a new grouping of macrophage populations based on three different homeostatic activities - host defence, wound healing and immune regulation. We propose that similarly to primary colours, these three basic macrophage populations can blend into various other 'shades' of activation. We characterize each population and provide examples of macrophages from specific disease states that have the characteristics of one or more of these populations.

7,384 citations

Journal ArticleDOI
27 May 2005-Science
TL;DR: Using in vivo two-photon imaging in neocortex, it is found that microglial cells are highly active in their presumed resting state, continually surveying their microenvironment with extremely motile processes and protrusions.
Abstract: Microglial cells represent the immune system of the mammalian brain and therefore are critically involved in various injuries and diseases. Little is known about their role in the healthy brain and their immediate reaction to brain damage. By using in vivo two-photon imaging in neocortex, we found that microglial cells are highly active in their presumed resting state, continually surveying their microenvironment with extremely motile processes and protrusions. Furthermore, blood-brain barrier disruption provoked immediate and focal activation of microglia, switching their behavior from patroling to shielding of the injured site. Microglia thus are busy and vigilant housekeepers in the adult brain.

4,458 citations

Journal ArticleDOI
05 Nov 2010-Science
TL;DR: Results identify microglia as an ontogenically distinct population in the mononuclear phagocyte system and have implications for the use of embryonically derived microglial progenitors for the treatment of various brain disorders.
Abstract: Microglia are the resident macrophages of the central nervous system and are associated with the pathogenesis of many neurodegenerative and brain inflammatory diseases; however, the origin of adult microglia remains controversial. We show that postnatal hematopoietic progenitors do not significantly contribute to microglia homeostasis in the adult brain. In contrast to many macrophage populations, we show that microglia develop in mice that lack colony stimulating factor-1 (CSF-1) but are absent in CSF-1 receptor-deficient mice. In vivo lineage tracing studies established that adult microglia derive from primitive myeloid progenitors that arise before embryonic day 8. These results identify microglia as an ontogenically distinct population in the mononuclear phagocyte system and have implications for the use of embryonically derived microglial progenitors for the treatment of various brain disorders.

3,894 citations

Journal ArticleDOI
28 May 2010-Immunity
TL;DR: In this paper, the authors assess recent research in this field, argue for a restricted definition, and explore pathways by which the T helper 2 (Th2) cell cytokines interleukin-4 (IL-4) and IL-13 mediate their effects on macrophage cell biology, their biosynthesis, and responses to a normal and pathological microenvironment.

3,450 citations