%0 Journal Article
%A Cangalaya, Carla
%A Sun, Weilun
%A Stoyanov, Stoyan Borislavov
%A Dunay, Ildiko Rita
%A Dityatev, Alexander
%T Integrity of neural extracellular matrix is required for microglia-mediated synaptic remodeling.
%J Glia
%V 72
%N 10
%@ 0894-1491
%C Bognor Regis [u.a.]
%I Wiley-Liss
%M DZNE-2024-01038
%P 1874 - 1892
%D 2024
%X 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.
%K Animals
%K Microglia: metabolism
%K Microglia: drug effects
%K Extracellular Matrix: metabolism
%K Extracellular Matrix: drug effects
%K Synapses: metabolism
%K Synapses: drug effects
%K Synapses: physiology
%K Complement C1q: metabolism
%K Mice, Inbred C57BL
%K Chondroitin ABC Lyase: pharmacology
%K Mice
%K Neuronal Plasticity: physiology
%K Neuronal Plasticity: drug effects
%K Complement C3: metabolism
%K Calreticulin: metabolism
%K Male
%K Phagocytosis: physiology
%K Phagocytosis: drug effects
%K Mice, Transgenic
%K Macrophage-1 Antigen: metabolism
%K C1q (Other)
%K C3 (Other)
%K complement protein (Other)
%K extracellular matrix (Other)
%K microglia (Other)
%K spine (Other)
%K synapse (Other)
%K two‐photon microscopy (Other)
%K Complement C1q (NLM Chemicals)
%K Chondroitin ABC Lyase (NLM Chemicals)
%K Complement C3 (NLM Chemicals)
%K Calreticulin (NLM Chemicals)
%K Macrophage-1 Antigen (NLM Chemicals)
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:38946065
%R 10.1002/glia.24588
%U https://pub.dzne.de/record/271336