The Lifespan and Turnover of Microglia in the Human Brain

Réu, Pedro; Khosravi, Azadeh; Bernard, Samuel; Mold, Jeff E.; Salehpour, Mehran; Alkass, Kanar; Perl, Shira; Tisdale, John F.; Possnert, Göran; Druid, Henrik; Frisén, Jonas

doi:10.1016/j.celrep.2017.07.004

Cited by 395 publications

(225 citation statements)

References 35 publications

(52 reference statements)

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“…Under homeostatic conditions, microglia are long-lived, selfrenewing cells. Although some studies suggest that microglia persist throughout the life of an individual (91), others show that their turnover rate is quite fast, at around 1% per day in the mouse (92,93) and 28% per year in the human (94). Regardless, their relatively long lifespan has been proposed to be crucial in microglial priming and ultimately contributing to neurodegeneration (91).…”

Section: Evidence For Cd11c+ Microglia Signature In Repopulation Studiesmentioning

confidence: 99%

Protective Microglial Subset in Development, Aging, and Disease: Lessons From Transcriptomic Studies

2020

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Microglial heterogeneity has been the topic of much discussion in the scientific community. Elucidation of their plasticity and adaptability to disease states triggered early efforts to characterize microglial subsets. Over time, their phenotypes, and later on their homeostatic signature, were revealed, through the use of increasingly advanced transcriptomic techniques. Recently, an increasing number of these "microglial signatures" have been reported in various homeostatic and disease contexts. Remarkably, many of these states show similar overlapping microglial gene expression patterns, both in homeostasis and in disease or injury. In this review, we integrate information from these studies, and we propose a unique subset, for which we introduce a core signature, based on our own research and reports from the literature. We describe that this subset is found in development and in normal aging as well as in diverse diseases. We discuss the functions of this subset as well as how it is induced.

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Section: Evidence For Cd11c+ Microglia Signature In Repopulation Studiesmentioning

confidence: 99%

Protective Microglial Subset in Development, Aging, and Disease: Lessons From Transcriptomic Studies

2020

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“…This pattern is striking given growing recognition that some neuropsychiatric disorders are linked to an underlying vulnerability, which likely begins perinatally, and a “second hit” that unmasks the full pathology [39]. Microglia are ideal candidates as a mechanism underlying priming, as they are macrophages that shift their function following immune stimulation, potentially permanently, in common with many immune cells; but they are also long-living cells [40,41], in contrast to most innate immune cell populations outside the brain. Notably, infection at a later stage of development, postnatal day (P)30, does not have the same persistent impact, implicating a critical window [42].…”

Section: Environmental Factors Affecting Microglial Developmentmentioning

confidence: 99%

Environment matters: microglia function and dysfunction in a changing world

Hanamsagar

Bilbo

2017

Current Opinion in Neurobiology

108

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The immune system is our interface with the environment, and immune molecules such as cytokines and chemokines and the cells that produce them within the brain, notably microglia, are critical for normal brain development. This recognition has in recent years led to the working hypothesis that inflammatory events during pregnancy or the early postnatal period, e.g. in response to infection, may disrupt the normal developmental trajectory of microglia and consequently their interactions with neurons, thereby contributing to the risk for neurological disorders. The current article outlines recent findings on the impact of diverse, pervasive environmental challenges, beyond infection, including air pollution and maternal stress; and their impact on microglial development and its broad implications for neural pathologies.

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“…They populate the developing CNS at early embryonic stages (Reemst et al, 2016) and expand by proliferation to eventually constitute 5-15% of total CNS cells in adulthood (Tay et al, 2016). Unlike other tissue macrophages, microglia persist for the life of the organism with slow turnover rates at steady state (Ajami et al, 2007;Askew et al, 2017;Réu et al, 2017;Tay et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

Developmental roles of microglia: A window into mechanisms of disease

Anderson

Vetter

2018

Developmental Dynamics

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Microglia are engineers of the CNS both in health and disease. In addition to the canonical immunological roles of clearing damaging entities and limiting the spread of toxicity and death, microglia remodel the CNS throughout life. While they have been extensively studied in disease and injury, due to their highly variable functions, their precise role in these contexts still remains uncertain. Over the last decade we have greatly expanded our understanding of microglial function, including their essential homeostatic roles during development. Here, we review these developmental roles, identify parallels in disease, and speculate whether developmental mechanisms reemerge in disease and injury.

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The Lifespan and Turnover of Microglia in the Human Brain

Cited by 395 publications

References 35 publications

Protective Microglial Subset in Development, Aging, and Disease: Lessons From Transcriptomic Studies

Protective Microglial Subset in Development, Aging, and Disease: Lessons From Transcriptomic Studies

Environment matters: microglia function and dysfunction in a changing world

Developmental roles of microglia: A window into mechanisms of disease

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