TY  - JOUR
AU  - Cangalaya, Carla
AU  - Sun, Weilun
AU  - Stoyanov, Stoyan Borislavov
AU  - Dunay, Ildiko Rita
AU  - Dityatev, Alexander
TI  - Integrity of neural extracellular matrix is required for microglia-mediated synaptic remodeling.
JO  - Glia
VL  - 72
IS  - 10
SN  - 0894-1491
CY  - Bognor Regis [u.a.]
PB  - Wiley-Liss
M1  - DZNE-2024-01038
SP  - 1874 - 1892
PY  - 2024
AB  - 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.
KW  - Animals
KW  - Microglia: metabolism
KW  - Microglia: drug effects
KW  - Extracellular Matrix: metabolism
KW  - Extracellular Matrix: drug effects
KW  - Synapses: metabolism
KW  - Synapses: drug effects
KW  - Synapses: physiology
KW  - Complement C1q: metabolism
KW  - Mice, Inbred C57BL
KW  - Chondroitin ABC Lyase: pharmacology
KW  - Mice
KW  - Neuronal Plasticity: physiology
KW  - Neuronal Plasticity: drug effects
KW  - Complement C3: metabolism
KW  - Calreticulin: metabolism
KW  - Male
KW  - Phagocytosis: physiology
KW  - Phagocytosis: drug effects
KW  - Mice, Transgenic
KW  - Macrophage-1 Antigen: metabolism
KW  - C1q (Other)
KW  - C3 (Other)
KW  - complement protein (Other)
KW  - extracellular matrix (Other)
KW  - microglia (Other)
KW  - spine (Other)
KW  - synapse (Other)
KW  - two‐photon microscopy (Other)
KW  - Complement C1q (NLM Chemicals)
KW  - Chondroitin ABC Lyase (NLM Chemicals)
KW  - Complement C3 (NLM Chemicals)
KW  - Calreticulin (NLM Chemicals)
KW  - Macrophage-1 Antigen (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:38946065
DO  - DOI:10.1002/glia.24588
UR  - https://pub.dzne.de/record/271336
ER  -