Microglia and macrophages in brain homeostasis and disease
Abstract
Microglia and non-parenchymal macrophages in the brain are mononuclear phagocytes that are increasingly recognized to be essential players in the development, homeostasis and diseases of the central nervous system. With the availability of new genetic, molecular and pharmacological tools, considerable advances have been made towards our understanding of the embryonic origins, developmental programmes and functions of these cells. These exciting discoveries, some of which are still controversial, also raise many new questions, which makes brain macrophage biology a fast-growing field at the intersection of neuroscience and immunology. Here, we review the current knowledge of how and where brain macrophages are generated, with a focus on parenchymal microglia. We also discuss their normal functions during development and homeostasis, the disturbance of which may lead to various neurodegenerative and neuropsychiatric diseases.
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Microglia clear myelin debris and influence oligodendrocytes and myelin formation in MS lesions.
“Accumulating evidence shows that microglia clear myelin debris and influence oligodendrocytes and myelin formation in MS lesions (Irfan et al. 2022; Li and Barres 2018).”
From Depletion of Microglia Increases Cortical Oligodendrocyte Density During Remyelination (2026) · cites this paper as Li and Barres 2018
Microglia arise from yolk sac erythromyeloid precursors and migrate into the brain parenchyma during early development.
“It is believed that microglia arise from yolk sac erythromyeloid precursors and migrate into the brain parenchyma during early development [43,44,45].”
From The Cuprizone Model: Dos and Do Nots (2020) · cites this paper as [43]
Under normal conditions, microglia help maintain homeostasis by providing neurotrophic support and clearing harmful substances, such as amyloid plaques, through phagocytosis.
“Under normal conditions, they help maintain homeostasis by providing neurotrophic support and clearing harmful substances, such as amyloid plaques, through phagocytosis [8, 9, 10].”
From Targeting Microglial Transcriptional Reprogramming as a Therapy Strategy for Alzheimer's Disease (2026) · cites this paper as [9]
These controversial outcomes highlight a complex dual role of microglia, also observed in other brain diseases, and might be attributed to total removal of microglia being harmful, whereas targeting specific microglia activation states later in disease might prolong survival time.
“These controversial outcomes highlight a complex dual role of microglia also observed in other brain diseases [54,55,56] and might be attributed to the fact that the total removal of microglia might be harmful, whereas targeting specific microglia activation states later in disease might prolong survival time.”
From Loss of Homeostatic Microglia Signature in Prion Diseases (2022) · cites this paper as [56]
Primary EMPs, secondary EMP-derived fetal liver monocytes, and HSC-derived fetal liver monocytes contribute to all tissue macrophages, with microglia arising solely from primary EMP.
“Thus, primary EMPs, secondary EMP-derived fetal liver monocytes, and HSC-derived fetal liver monocytes contribute to all tissue macrophages, with microglia arising solely from primary EMP.”
From Microglia in neurodegenerative diseases: mechanism and potential therapeutic targets (2023) · cites this paper as [41]
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The Cuprizone Model: Dos and Do Nots
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“Consequently, microglia have often been implicated in neurodegenerative and neuropsychiatric diseases [2, 3].”
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Emerging role of the P2X7-NLRP3-IL1β pathway in mood disorders
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Inflammation within the neurovascular unit: Focus on microglia for stroke injury and recovery
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The Translational Potential of Microglia and Monocyte-Derived Macrophages in Ischemic Stroke
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“In disease states, they take on ‘activated’ features characterized by rapid proliferation, migration, antigen presentation to infiltrating immune cells, and secretion of proinflammatory cytokines, chemokines, and reactive oxygen species [1].”
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Microglia Dystrophy Following Binge-Like Alcohol Exposure in Adolescent and Adult Male Rats
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miR-142-3p Regulates BDNF Expression in Activated Rodent Microglia Through Its Target CAMK2A
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Loss of microglial EED impairs synapse density, learning, and memory
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MiR-124 and MiR-155 as Therapeutic Targets in Microglia-Mediated Inflammation in Multiple Sclerosis
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“As the resident immune cells of the brain, microglia function in the surveillance of the brain milieu to respond to injury or disease (Andjelkovic et al., 1998; Li and Barres, 2018).”
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Loss of Homeostatic Microglia Signature in Prion Diseases
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INPP5D/SHIP1 regulates inflammasome activation in human microglia
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Depletion of Microglia Increases Cortical Oligodendrocyte Density During Remyelination
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- Authors
- Li, Q., & Barres, B. A.
- Affiliations
- Stanford Medicine (US)
- Corresponding author
- Li, Qingyun
- Barres, Ben A.
- Venue
- Nature Reviews Immunology
- Published
- 2017-11-20
- Volume
- 18
- Issue
- 4
- Pages
- 225-242
- ISSN
- 1474-1733 (ISSN-L)
- 1474-1741
- OpenAlex
- W2769071992
- Semantic Scholar
- 89cc0a9647c1321c47810ac3be02ac189dd60e22
- Cited by
- 1,999
- References
- 64
- Citations by year
- 2026: 181 · 2025: 266 · 2024: 302 · 2023: 255 · 2022: 298 · 2021: 270 · 2020: 211 · 2019: 134 · 2018: 80 · 2017: 1
- FWCI
- 11.24
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature reviews. Immunology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
- Keywords
- microglia, mononuclear phagocytes, brain development, brain homeostasis, neurodegenerative diseases, neuropsychiatric disorders, neuroinflammation
- MeSH terms
- Animals, Brain, Brain Diseases, Cell Differentiation, Homeostasis, Humans, Macrophages, Models, Neurological, Microglia, Models, Immunological
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