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Updated: Mar 11, 2026
Isolation of Cortical Microglia with Preserved Immunophenotype and Functionality From Murine Neonates
Published on: January 30, 2014
P2Y12 receptor is expressed on human microglia under physiological conditions throughout development and is sensitive
Alexander Mildner1, Hao Huang1, Josefine Radke2,3,4
1Department of Neuropsychiatry and Laboratory of Molecular Psychiatry, Charité-Universitätsmedizin Berlin, Berlin, 10117, Germany.
Abstract:
Microglia are resident immune cells in the central nervous system (CNS), which are essential for immune defence and critically contribute to neuronal functions during homeostasis. Until now, little is known about microglia biology in humans in part due to the lack of microglia-specific markers. We therefore investigated the expression of the purinergic receptor P2Y12 in human brain tissue. Compared to classical markers used to identify microglia such as Iba1, CD68 or MHCII, we found that P2Y12 is expressed on parenchymal microglia but is absent from perivascular or meningeal macrophages. We further demonstrate that P2Y12 expression is stable throughout human brain development, including fetal phases, and quantification of P2 Y12+ microglia revealed that the density of human microglia is constant throughout lifetime. In contrast, CD68 expression increases during aging in cerebellar but not in cortical microglia, indicating regional heterogeneity. CNS pathologies such as Alzheimer's disease or multiple sclerosis-but not schizophrenia-result in decreased P2Y12 immunoreactivity in plaque- or lesion-associated myeloid cells, whereas Iba1 expression remains detectable. Our results suggest that P2Y12 is a useful marker for the identification of human microglia throughout the lifespan. Moreover, P2Y12 expression might help to discriminate activated microglia and infiltrating myeloid cells from quiescent microglia in the human CNS. GLIA 2017;65:375-387.
Insights
The purinergic receptor P2Y12 is a stable marker for human microglia across the lifespan. This marker helps distinguish microglia from other myeloid cells in the central nervous system (CNS).
Area of Science:
- Neuroscience
- Immunology
- Cell Biology
Background:
- Microglia, the resident immune cells of the central nervous system (CNS), play crucial roles in immune defense and neuronal function.
- Identifying specific human microglia markers has been challenging, limiting our understanding of their biology.
- Classical markers like Iba1, CD68, and MHCII have limitations in specificity and stability.
Purpose of the Study:
- To investigate the expression and utility of the purinergic receptor P2Y12 as a specific marker for human microglia.
- To compare P2Y12 expression with classical microglial markers in human brain tissue.
- To assess the stability of P2Y12 expression throughout human development and aging, and in CNS pathologies.
Main Methods:
- Immunohistochemical analysis of human brain tissue.
- Comparison of P2Y12 expression with Iba1, CD68, and MHCII.
- Evaluation of P2Y12 expression in different brain regions, developmental stages, and in CNS diseases like Alzheimer's and multiple sclerosis.
Main Results:
- P2Y12 is expressed on parenchymal microglia but not on perivascular or meningeal macrophages, unlike Iba1, CD68, or MHCII.
- P2Y12 expression remains stable throughout human brain development, from fetal stages to old age.
- Microglial density is constant throughout life, while CD68 expression varies regionally and increases with age.
- P2Y12 immunoreactivity decreases in plaque- or lesion-associated myeloid cells in Alzheimer's disease and multiple sclerosis, while Iba1 remains detectable.
Conclusions:
- P2Y12 is a reliable and stable marker for identifying human microglia across the lifespan.
- P2Y12 can differentiate quiescent microglia from activated microglia and infiltrating myeloid cells in the human CNS.
- This marker enhances the study of human microglia biology and their roles in health and disease.
