Factors regulating microglia activation
Open accessAbstract
Microglia are resident macrophages of the central nervous system (CNS) that display high functional similarities to other tissue macrophages. However, it is especially important to create and maintain an intact tissue homeostasis to support the neuronal cells, which are very sensitive even to minor changes in their environment. The transition from the "resting" but surveying microglial phenotype to an activated stage is tightly regulated by several intrinsic (e.g., Runx-1, Irf8, and Pu.1) and extrinsic factors (e.g., CD200, CX3CR1, and TREM2). Under physiological conditions, minor changes of those factors are sufficient to cause fatal dysregulation of microglial cell homeostasis and result in severe CNS pathologies. In this review, we discuss recent achievements that gave new insights into mechanisms that ensure microglia quiescence.
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This highlights age-dependent change in microglial plasticity.
“highlighting the age-dependent change in microglial plasticity [53, 55].”
From Transcriptional and Epigenetic Regulation of Microglia in Health and Disease (2019) · cites this paper as [55]
Expression of microglial surface receptors CX3CR1, P2RY12, and TREM2 and TLRs tends to negatively correlate with age.
“Further analysis revealed that microglia surface receptors for microglia-neuron crosstalk (CX3CR1, P2RY12, and TREM2) and TLRs for communication with pathogen-associated molecular patterns tended to show a negative correlation between gene expression level and age, highlighting the age-dependent change in microglial plasticity [53, 55].”
From Transcriptional and Epigenetic Regulation of Microglia in Health and Disease (2019) · cites this paper as [55]
This suggests a reactive state and reduced plasticity in adult microglia, possibly due to repeated infections and debris clearance.
“suggesting their reactive state and reduced plasticity in the adult stage possibly due to repetitive exposure to infectious agents and active removal of cell debris [53, 55].”
From Transcriptional and Epigenetic Regulation of Microglia in Health and Disease (2019) · cites this paper as [55]
During maturation and aging, pro-inflammatory gene expression increases in adult microglia.
“With maturation and aging, expression of pro-inflammatory genes in adult microglia increase, suggesting their reactive state and reduced plasticity in the adult stage possibly due to repetitive exposure to infectious agents and active removal of cell debris [53, 55].”
From Transcriptional and Epigenetic Regulation of Microglia in Health and Disease (2019) · cites this paper as [55]
Microglia account for approximately 5-12% of total brain cells and are distributed unevenly, with greater densities in grey matter and structures such as hippocampus, basal ganglia, and substantia nigra than in white matter.
“Microglia represent a heterogeneous cell population accounting for approximately 5–12% of total brain cells. They are distributed unevenly throughout the CNS, as grey matter and specific structures such as the hippocampus, basal ganglia, and substantia nigra typically all exhibit greater densities than the white matter (58–60).”
From The HPA – Immune Axis and the Immunomodulatory Actions of Glucocorticoids in the Brain (2014) · cites this paper as [59]
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Site-Specific Regulation of P2X7 Receptor Function in Microglia Gates Morphine Analgesic Tolerance
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Borjini, N., Fernández, M., Giardino, L., & Calzà, L. (2016) · Journal of Neuroinflammation · doi:10.1186/s12974-016-0757-6 · Cited by 61 · see citing works
- Authors
- Kierdorf, K., & Prinz, M.
- Affiliations
- University of Freiburg (DE)
- Corresponding author
- Prinz, Marco
- Venue
- Frontiers in Cellular Neuroscience
- Publisher
- Frontiers Media SA
- Published
- 2013
- Volume
- 7
- Pages
- 44-44
- ISSN
- 1662-5102 (ISSN-L)
- PMC
- PMC3632747
- OpenAlex
- W2149538964
- Cited by
- 360
- References
- 83
- Citations by year
- 2026: 11 · 2025: 19 · 2024: 21 · 2023: 22 · 2022: 22 · 2021: 43 · 2020: 40 · 2019: 30 · 2018: 30 · 2017: 28 · 2016: 23 · 2015: 31 · 2014: 31 · 2013: 7
- FWCI
- 17.17
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- Frontiers in Cellular Neuroscience (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Deutsche Forschungsgemeinschaft (PR 577/8-2)
- Bundesministerium für Bildung und Forschung (PR 577/8-2)
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Inflammasome and immune disorders
- Life Sciences › Immunology and Microbiology › Immunology › Phagocytosis and Immune Regulation
- Keywords
- microglial activation, microglial homeostasis, central nervous system, IRF8, PU.1, CD200, CX3CR1, TREM2, neuroinflammation, CNS pathology
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