001     271336
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024 7 _ |a 10.1002/glia.24588
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024 7 _ |a pmid:38946065
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024 7 _ |a 1098-1136
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037 _ _ |a DZNE-2024-01038
041 _ _ |a English
082 _ _ |a 610
100 1 _ |a Cangalaya, Carla
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245 _ _ |a Integrity of neural extracellular matrix is required for microglia-mediated synaptic remodeling.
260 _ _ |a Bognor Regis [u.a.]
|c 2024
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520 _ _ |a Microglia continuously remodel synapses, which are embedded in the extracellular matrix (ECM). However, the mechanisms, which govern this process remain elusive. To investigate the influence of the neural ECM in synaptic remodeling by microglia, we disrupted ECM integrity by injection of chondroitinase ABC (ChABC) into the retrosplenial cortex of healthy adult mice. Using in vivo two-photon microscopy we found that ChABC treatment increased microglial branching complexity and ECM phagocytic capacity and decreased spine elimination rate under basal conditions. Moreover, ECM attenuation largely prevented synaptic remodeling following synaptic stress induced by photodamage of single synaptic elements. These changes were associated with less stable and smaller microglial contacts at the synaptic damage sites, diminished deposition of calreticulin and complement proteins C1q and C3 at synapses and impaired expression of microglial CR3 receptor. Thus, our findings provide novel insights into the function of the neural ECM in deposition of complement proteins and synaptic remodeling by microglia.
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650 _ 7 |a C1q
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650 _ 7 |a C3
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650 _ 7 |a complement protein
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650 _ 7 |a extracellular matrix
|2 Other
650 _ 7 |a microglia
|2 Other
650 _ 7 |a spine
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650 _ 7 |a synapse
|2 Other
650 _ 7 |a two‐photon microscopy
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650 _ 7 |a Complement C1q
|0 80295-33-6
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650 _ 7 |a Chondroitin ABC Lyase
|0 EC 4.2.2.20
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650 _ 7 |a Complement C3
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650 _ 7 |a Calreticulin
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650 _ 7 |a Macrophage-1 Antigen
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650 _ 2 |a Animals
|2 MeSH
650 _ 2 |a Microglia: metabolism
|2 MeSH
650 _ 2 |a Microglia: drug effects
|2 MeSH
650 _ 2 |a Extracellular Matrix: metabolism
|2 MeSH
650 _ 2 |a Extracellular Matrix: drug effects
|2 MeSH
650 _ 2 |a Synapses: metabolism
|2 MeSH
650 _ 2 |a Synapses: drug effects
|2 MeSH
650 _ 2 |a Synapses: physiology
|2 MeSH
650 _ 2 |a Complement C1q: metabolism
|2 MeSH
650 _ 2 |a Mice, Inbred C57BL
|2 MeSH
650 _ 2 |a Chondroitin ABC Lyase: pharmacology
|2 MeSH
650 _ 2 |a Mice
|2 MeSH
650 _ 2 |a Neuronal Plasticity: physiology
|2 MeSH
650 _ 2 |a Neuronal Plasticity: drug effects
|2 MeSH
650 _ 2 |a Complement C3: metabolism
|2 MeSH
650 _ 2 |a Calreticulin: metabolism
|2 MeSH
650 _ 2 |a Male
|2 MeSH
650 _ 2 |a Phagocytosis: physiology
|2 MeSH
650 _ 2 |a Phagocytosis: drug effects
|2 MeSH
650 _ 2 |a Mice, Transgenic
|2 MeSH
650 _ 2 |a Macrophage-1 Antigen: metabolism
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700 1 _ |a Sun, Weilun
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700 1 _ |a Stoyanov, Stoyan Borislavov
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700 1 _ |a Dunay, Ildiko Rita
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700 1 _ |a Dityatev, Alexander
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773 _ _ |a 10.1002/glia.24588
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