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Updated: Jun 8, 2026
Correlative Light and Electron Microscopy to Study Microglial Interactions with β-Amyloid Plaques
Published on: June 1, 2016
Midbrain extracellular matrix and microglia are associated with cognition in aging mice
Daniel T Gray1, Abigail Gutierrez2, Yasaman Jami-Alahmadi3
1Department of Physiology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA. dtgray@mednet.ucla.edu.
Abstract:
Synapse dysfunction is tightly linked to cognitive changes during aging. Emerging evidence suggests that microglia and the extracellular matrix (ECM) can potently regulate synapse integrity and plasticity. Yet the brain ECM, and its relationship with microglia, synapses, and cognition during aging remains virtually unexplored. In this study we combine ECM-optimized proteomic workflows with histological analyses in aging mice and discover regional differences in ECM composition and aging-induced ECM remodeling across basal ganglia nuclei. Moreover, we combine two distinct behavioral classification strategies with fixed-tissue confocal imaging and proteomic analysis and identify relationships between the hyaluronan- and proteoglycan-rich ECM and cognitive aging phenotypes. Finally, we provide evidence that aging midbrain microglia lose capacity to interact with and regulate the ECM, and that these aging-associated microglial changes are accompanied by local ECM accumulation and worse behavioral performance. Together, these observations indicate that changing microglia-ECM-synapse interactions contribute to cognitive functioning during healthy aging.
Insights
Aging brains show altered extracellular matrix (ECM) and microglia interactions, impacting synapse function and cognition. These changes in microglia-ECM-synapse dynamics contribute to cognitive aging phenotypes.
Area of Science:
- Neuroscience
- Aging Research
- Molecular Biology
Background:
- Synapse dysfunction is linked to cognitive decline in aging.
- Microglia and the extracellular matrix (ECM) influence synapse integrity.
- The role of brain ECM in aging and cognition is largely unknown.
Purpose of the Study:
- To investigate the brain ECM's role in aging and cognition.
- To explore the relationship between microglia, ECM, and cognitive aging.
- To identify how ECM composition changes with age and impacts brain function.
Main Methods:
- Used ECM-optimized proteomic workflows and histological analyses in aging mice.
- Combined behavioral classification with confocal imaging and proteomic analysis.
- Examined microglia-ECM interactions in aging brain tissue.
Main Results:
- Discovered regional differences in ECM composition and remodeling in aging basal ganglia.
- Identified links between ECM composition (hyaluronan- and proteoglycan-rich) and cognitive aging phenotypes.
- Showed aging microglia lose ECM interaction capacity, leading to ECM accumulation and worse performance.
Conclusions:
- Microglia-ECM-synapse interactions are crucial for cognitive function during aging.
- Altered ECM and impaired microglia function contribute to cognitive aging.
- This study reveals novel insights into the molecular mechanisms of cognitive aging.
