ArticleScientific reports2025
Microglial depletion increases aggrecan and hyaluronan levels in the diffuse and aggregated extracellular matrix of the mouse brain.
Article in Scientific reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed.
- Hypothalamic neurovascular and extracellular matrix remodeling: Cellular niche orchestration of immune-metabolic adaptation to nutritional stress.Reviews in endocrine & metabolic disorders · 2026Review
- Microglia-mediated synaptic pruning in neural circuit remodeling: multidimensional control in homeostasis and neuropathology.BMC medicine · 2026Review
- Epigenetic Regulation of Hyaluronan-Associated Genes in the Brain: Identifying Key Regulatory Sites.Epigenomes · 2026Review
- Microglia-Mediated Phagocytosis in Alzheimer's Disease: Mechanisms, Heterogeneity, and Therapeutic Insights.Biomolecules · 2025Review
- Increased levels of HAPLN2, which anchors dense extracellular matrix, in the hippocampus of APOE4 targeted replacement mice.bioRxiv : the preprint server for biology · 2025Article
- Aggrecan protects against plaque accumulation and is essential for proper microglial responses to plaques.Cell reports · 2025Article
- Exploring the Role of the Extracellular Matrix in Disease and Aging.Juntendo medical journal · 2025Article
Corrections and comments
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Authors and funding
6 authors.
Funding
Abstract
The extracellular matrix (ECM) in the brain can be divided into aggregated ECM, such as perineuronal nets (PNNs) around neurons, and diffuse ECM, which is present throughout the brain parenchyma. Both aggregated and diffuse ECM restrict synaptic plasticity and stabilize neural circuits in the adult brain. Hyaluronan (HA) acts as a scaffold for the brain ECM, and multiple proteoglycans, such as aggrecan, bind to HA to form a macromolecular complex. Recent evidence suggests that microglia, the resident immune cells of the brain, play a crucial role in ECM homeostasis. However, it remains unclear how microglia influence the molecular composition of the ECM. Using a tissue-clearing technique and histochemical analysis, we found that microglial depletion increased the staining intensity of aggrecan and HA in both PNNs and diffuse ECM. Biochemical analyses further confirmed the accumulation of the aggrecan core protein and HA following microglial depletion. Our findings highlight the essential role of microglia in regulating the ECM composition and provide new insights into the mechanisms by which microglia influence neuronal function.
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Registered trials
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