Visualizing Dark Microglia
Abstract
Dark microglia, a recently described phenotype, are found in high numbers in nonhomeostatic conditions (e.g., Alzheimer's disease pathology, aging, chronic stress). As a specific protein marker has not yet been defined, they cannot be studied using conventional cellular biology techniques. They are recognized by their unique ultrastructural features visible under electron microscopy. This nanoscale resolution imaging technique allows the identification of cells based on their ultrastructure or immunoreactivity to certain proteins. In this protocol, we describe the steps necessary for the preparation of high-quality brain tissues for transmission electron microscopy, the imaging, the identification of dark microglia, and the ultrastructural analysis of various parameters that can be studied in these cells.
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Microglia promote and assist various processes within the CNS, closely interacting with neurons, other glial cells, the neurovascular unit and the extracellular matrix.
“Microglia promote and assist with various processes within the CNS, closely interacting with neurons, other glial cells, the neurovascular unit and the extracellular matrix.”
From Sex chromosomes and sex hormones differently shape microglial properties during normal physiological conditions in the adult mouse hippocampus (2025) · cites this paper as [27]
Microglia regulate axonal myelination, synaptic pruning, vasculature repair, and clearance of debris and toxic substances.
“These cells not only regulate axonal myelination, but also contribute to synaptic pruning, vasculature repair, and clearance of debris and toxic substances, among other important physiological roles [23–28].”
From Sex chromosomes and sex hormones differently shape microglial properties during normal physiological conditions in the adult mouse hippocampus (2025) · cites this paper as [27]
Cites
Dark microglia: A new phenotype predominantly associated with pathological states
Bisht, K., Sharma, K. P., Lecours, C., Gabriela Sánchez, M., El Hajj, H., Milior, G., Olmos‐Alonso, A., Gómez‐Nicola, D., Luheshi, G., Vallières, L., et al. (2016) · Glia · doi:10.1002/glia.22966 · Cited by 421 · see citing works
Self-citationEskelinen, E.-L. (2008) · Autophagy · doi:10.4161/auto.5179 · Cited by 197 · see citing works
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Impact of TREM2R47H variant on tau pathology–induced gliosis and neurodegeneration
Gratuze, M., Leyns, C. E. G., Sauerbeck, A. D., St-Pierre, M.-K., Xiong, M., Kim, N., Serrano, J. R., Tremblay, M.-È., Kummer, T. T., Colonna, M., et al. (2020) · Journal of Clinical Investigation · doi:10.1172/jci138179 · Cited by 252 · see citing works
Self-citationBobotis, B. C., Khakpour, M., Braniff, O., de Andrade, E. G., Gargus, M., Allen, M., Carrier, M., Baillargeon, J., Rangachari, M., & Tremblay, M.-È. (2025) · Journal of Neuroinflammation · doi:10.1186/s12974-025-03341-6 · Cited by 17 · see citing works
“Autophagosomes were identified by their double-membrane enclosure [28, 27, 57].”
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- Authors
- St-Pierre, M.-K., Bordeleau, M., & Tremblay, M.-È.
- Affiliations
- Douglas Mental Health University Institute (CA)
- Université Laval (CA)
- Corresponding author
- Tremblay, Marie-Ève
- ORCID
- Tremblay, Marie-Ève
- Venue
- Methods in Molecular Biology
- Publisher
- Springer New York
- Published
- 2019
- Volume
- 2034
- Pages
- 97-110
- ISSN
- 1064-3745 (ISSN-L)
- 1940-6029
- OpenAlex
- W2965768470
- Cited by
- 53
- References
- 2
- Citations by year
- 2026: 8 · 2025: 6 · 2024: 9 · 2023: 6 · 2022: 9 · 2021: 10 · 2020: 5
- FWCI
- 7.55
- Type
- book chapter
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Methods in molecular biology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Canadian Institutes of Health Research
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
- Keywords
- transmission electron microscopy, brain tissue preparation, Alzheimer's disease, aging, chronic stress, immunoreactivity
- MeSH terms
- Alzheimer Disease, Animals, Brain, Microglia, Microscopy, Electron, Transmission
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