Investigating Microglial Ultrastructural Alterations and Intimate Relationships with Neuronal Stress, Dystrophy, and Degeneration in Mouse Models of Alzheimer’s Disease
Abstract
In recent decades, microglia have taken the field of neuroscience by storm, with numerous studies identifying key roles for these cells in the pathophysiology of neurodegenerative conditions, such as Alzheimer's disease (AD). The heterogeneity of these cells (e.g., the presence of various subtypes like the disease-associated microglia, microglia associated with neurodegeneration, dark microglia, lipid droplet-accumulating microglia), and their ultrastructural alterations arising from environmental challenges have become a central focus of recent studies. Dark microglia are electron-dense cells defined by their ultrastructural markers of cellular stress using electron microscopy (EM). In this protocol, we first describe the steps required for proper brain tissue preparation for EM experiments. Ultrastructural analysis of microglia and neurons/synapses in AD mouse models is also detailed, using transmission or scanning EM. We next explain how to characterize several ultrastructural markers of cellular stress, dystrophy or degeneration, in microglia and neurons/synapses, with relation to amyloid beta plaques.
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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 [28]
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 [28]
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- Authors
- St-Pierre, M.-K., Carrier, M., Lau, V., & Tremblay, M.-È.
- Affiliations
- University of Victoria (CA)
- Simon Fraser University (CA)
- University of British Columbia (CA)
- Corresponding author
- Tremblay, Marie-Ève
- Venue
- Methods in Molecular Biology
- Publisher
- Springer US
- Published
- 2022
- Volume
- 2515
- Pages
- 29-58
- ISSN
- 1064-3745 (ISSN-L)
- 1940-6029
- OpenAlex
- W4285164101
- Cited by
- 29
- References
- 11
- Citations by year
- 2026: 6 · 2025: 7 · 2024: 8 · 2023: 6 · 2022: 2
- FWCI
- 12.84
- Type
- book chapter
- Language
- en
- Open access
- closed
- Locations
- Methods in molecular biology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Canadian Institutes of Health Research
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
- Keywords
- microglia, Alzheimer's disease, cellular stress, neuronal dystrophy, neurodegeneration, amyloid plaques, synapses, disease-associated microglia, mouse model
- MeSH terms
- Alzheimer Disease, Animals, Disease Models, Animal, Neurons, Amyloid beta-Peptides, Microglia, Mice, Plaque, Amyloid
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