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Cited by 165Neuroinflammation and Neurodegeneration MechanismsNeuroscience and Neuropharmacology ResearchBarrier Structure and Function Studies

The DOI matches its Crossref record; 190 of the 190 references it cites were found in a registry or an index.

Microglia and Astrocyte Function and Communication: What Do We Know in Humans?

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Garland, Emma F., Hartnell, Iain J., Boche, Delphine·2022·Frontiers in Neuroscience
DOI 10.3389/fnins.2022.824888PMC PMC8888691
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Abstract

Microglia and astrocytes play essential roles in the central nervous system contributing to many functions including homeostasis, immune response, blood–brain barrier maintenance and synaptic support. Evidence has emerged from experimental models of glial communication that microglia and astrocytes influence and coordinate each other and their effects on the brain environment. However, due to the difference in glial cells between humans and rodents, it is essential to confirm the relevance of these findings in human brains. Here, we aim to review the current knowledge on microglia-astrocyte crosstalk in humans, exploring novel methodological techniques used in health and disease conditions. This will include an in-depth look at cell culture and iPSCs, post-mortem studies, imaging and fluid biomarkers, genetics and transcriptomic data. In this review, we will discuss the advantages and limitations of these methods, highlighting the understanding these methods have brought the field on these cells communicative abilities, and the knowledge gaps that remain.

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Crossref · 10.3389/fnins.2022.824888

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FIGURE 1 Functional and morphological characteristics of microglia and astrocytes. AD, Alzheimer’s disease; PD, Parkinson’s disease; HD, Huntington’s disease; MND, motor neuron disease; FTD, frontotemporal dementia; MS, multiple sclerosis. Microglia phenotypes have been disputed and may not reflect their functions.
FIGURE 1 Functional and morphological characteristics of microglia and astrocytes. AD, Alzheimer’s disease; PD, Parkinson’s disease; HD, Huntington’s disease; MND, motor neuron disease; FTD, frontotemporal dementia; MS, multiple sclerosis. Microglia phenotypes have been disputed and may not reflect their functions.CC BY · PubMed Central
FIGURE 2 GFAP+ stained astrocyte subtypes. (A) Protoplasmic astrocytes of the gray matter. Note the lighter staining, showing less expression of GFAP. (B) Darker stained fibrous astrocytes of the white matter. (C) Intralaminar astrocytes stretching process from layer I–II to layers III and IV. (D) Varicose projection astrocyte. Black arrows point to varicosities on the straight primary process. White arrow points to faintly stained cell body. [Scale bar (A,B) = 50 μm, (C) = 100 μm, (D) = 25 μm].
FIGURE 2 GFAP+ stained astrocyte subtypes. (A) Protoplasmic astrocytes of the gray matter. Note the lighter staining, showing less expression of GFAP. (B) Darker stained fibrous astrocytes of the white matter. (C) Intralaminar astrocytes stretching process from layer I–II to layers III and IV. (D) Varicose projection astrocyte. Black arrows point to varicosities on the straight primary process. White arrow points to faintly stained cell body. [Scale bar (A,B) = 50 μm, (C) = 100 μm, (D) = 25 μm].CC BY · PubMed Central
FIGURE 3 Expression of GFAP+ astrocytes. Astrocytes in control cases (A) and Pick’s disease cases (B), with the latter showing darker staining and greater cell number. Scale bars = 50 μm.
FIGURE 3 Expression of GFAP+ astrocytes. Astrocytes in control cases (A) and Pick’s disease cases (B), with the latter showing darker staining and greater cell number. Scale bars = 50 μm.CC BY · PubMed Central
FIGURE 4 Expression of Iba1+ microglia. Microglia in controls (A) and Alzheimer’s disease (B). Cells in (B) appear to have thicker processes. Scale bars = 50 μm.
FIGURE 4 Expression of Iba1+ microglia. Microglia in controls (A) and Alzheimer’s disease (B). Cells in (B) appear to have thicker processes. Scale bars = 50 μm.CC BY · PubMed Central
FIGURE 5 Known communication pathway between microglia and astrocytes in the human brain in response to disease. Receptors (underlined) and the signaling molecules (italic) are shown with the color of the arrow denoting the cell source (green = astrocytes, blue = microglia). The resulting phenotypic changes or movements are shown by gray arrows (single or triple, respectively). As microglia become activated by PAMP/DAMP signaling via TLR receptors (both blue), they become activated (gray arrow). Activated microglia release IL1β and TNFα which bind through IL1R and TNFR receptors to activate astrocytes and other microglial cells. This signaling with the addition of C1q signaling on astrocytes leads to a neurotoxic phenotype, with a loss of neuroprotective functions. Activated astrocytes release IL1β and TNFα to propagate a neuroinflammatory response. They also release ATP which binds to P2XR receptors on microglia, leading to extracellular vesicle release. Activated astrocytes and microglia may also release chemokines (CCL2–CCL5) which bind to receptors on microglia (CCR1–CCR5) and stimulate their chemotaxis toward the site of injury/pathogen. Inflammation is in part resolved by CD200 binding to CD200R on activated microglia, leading them to return to a homeostatic phenotype.
FIGURE 5 Known communication pathway between microglia and astrocytes in the human brain in response to disease. Receptors (underlined) and the signaling molecules (italic) are shown with the color of the arrow denoting the cell source (green = astrocytes, blue = microglia). The resulting phenotypic changes or movements are shown by gray arrows (single or triple, respectively). As microglia become activated by PAMP/DAMP signaling via TLR receptors (both blue), they become activated (gray arrow). Activated microglia release IL1β and TNFα which bind through IL1R and TNFR receptors to activate astrocytes and other microglial cells. This signaling with the addition of C1q signaling on astrocytes leads to a neurotoxic phenotype, with a loss of neuroprotective functions. Activated astrocytes release IL1β and TNFα to propagate a neuroinflammatory response. They also release ATP which binds to P2XR receptors on microglia, leading to extracellular vesicle release. Activated astrocytes and microglia may also release chemokines (CCL2–CCL5) which bind to receptors on microglia (CCR1–CCR5) and stimulate their chemotaxis toward the site of injury/pathogen. Inflammation is in part resolved by CD200 binding to CD200R on activated microglia, leading them to return to a homeostatic phenotype.CC BY · PubMed Central

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Metadata

Authors
Garland, E. F., Hartnell, I. J., & Boche, D.
Affiliations
University of Southampton (GB)
Corresponding author
Boche, Delphine
ORCID
Venue
Frontiers in Neuroscience
Publisher
Frontiers Media SA
Published
2022-02-16
Volume
16
Pages
824888-824888
ISSN
1662-453X (ISSN-L)
DOI
10.3389/fnins.2022.824888
PMC
PMC8888691
OpenAlex
W4212929528
Cited by
165
References
190
Citations by year
2026: 39 · 2025: 40 · 2024: 50 · 2023: 28 · 2022: 8
FWCI
3.27
Type
journal article
Language
en
Open access
Licence
Locations
  • Frontiers in Neuroscience (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • White Rose Research Online (University of Leeds, The University of Sheffield, University of York) (acceptedVersion)
  • ePrints Soton (University of Southampton) (acceptedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
Alzheimer’s Research UK
Topics
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
Keywords
microglia, astrocytes, human brain, blood-brain barrier, neuroinflammation, induced pluripotent stem cells, cell culture model, fluid biomarkers, transcriptomics, neurodegenerative diseases

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