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Advances in Visualizing Microglial Cells in Human Central Nervous System Tissue
Christopher E G Uff1,2, Karishma Patel3, Charming Yeung1
1Centre for Neuroscience, Surgery and Trauma, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London E1 2AT, UK.
Abstract:
Neuroinflammation has recently been identified as a fundamentally important pathological process in most, if not all, CNS diseases. The main contributor to neuroinflammation is the microglia, which constitute the innate immune response system. Accurate identification of microglia and their reactivity state is therefore essential to further our understanding of CNS pathophysiology. Many staining techniques have been used to visualise microglia in rodent and human tissue, and immunostaining is currently the most frequently used. Historically, identification of microglia was predominantly based on morphological structure, however, recently there has been a reliance on selective antigen expression, and microglia-specific markers have been identified providing increased certainty that the cells observed are in fact microglia, rather than the similar yet distinct macrophages. To date, the most microglia-specific markers are P2Y12 and TMEM119. However, other microglia-related markers can also be useful for demonstrating activation state, phagocytic state, and for neuroimaging purposes in longitudinal studies. Overall, it is important to be aware of the microglia-selectivity issues of the various stains and immunomarkers used by researchers to distinguish microglia in CNS tissue to avoid misinterpretation.
Insights
Accurate identification of microglia, the brain's immune cells, is crucial for understanding central nervous system (CNS) diseases. Researchers increasingly use specific markers like P2Y12 and TMEM119 to distinguish microglia from other cells.
Area of Science:
- Neuroscience
- Immunology
- Pathology
Background:
- Neuroinflammation is a key pathological process in central nervous system (CNS) diseases.
- Microglia are the primary immune cells in the CNS and critical mediators of neuroinflammation.
- Accurate identification of microglia and their activation states is essential for understanding CNS pathophysiology.
Purpose of the Study:
- To review current methods for identifying microglia in CNS tissue.
- To highlight the importance of microglia-specific markers for accurate diagnosis and research.
- To discuss potential misinterpretations arising from non-specific staining techniques.
Main Methods:
- Review of various staining techniques used for microglia visualization in rodent and human CNS tissue.
- Focus on immunostaining methods and the evolution from morphological identification to antigen-specific markers.
- Discussion of microglia-specific markers, including P2Y12 and TMEM119, and other activation-related markers.
Main Results:
- Immunostaining is the most common method for visualizing microglia.
- Reliance has shifted from morphology to selective antigen expression for higher certainty.
- P2Y12 and TMEM119 are currently the most microglia-specific markers identified.
- Other markers can indicate microglia activation and phagocytic states, useful for neuroimaging.
Conclusions:
- Accurate microglia identification is vital for CNS disease research.
- Microglia-specific markers like P2Y12 and TMEM119 enhance diagnostic certainty.
- Awareness of marker selectivity is crucial to avoid misinterpretation in CNS tissue analysis.
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