TY  - JOUR
AU  - Cangalaya, Carla
AU  - Wegmann, Susanne
AU  - Sun, Weilun
AU  - Diez, Lisa
AU  - Gottfried, Anna
AU  - Richter, Karin
AU  - Stoyanov, Stoyan
AU  - Pakan, Janelle
AU  - Fischer, Klaus-Dieter
AU  - Dityatev, Alexander
TI  - Real-time mechanisms of exacerbated synaptic remodeling by microglia in acute models of systemic inflammation and tauopathy.
JO  - Brain, behavior and immunity
VL  - 110
SN  - 0889-1591
CY  - Orlando, Fla.
PB  - Academic Press
M1  - DZNE-2023-00468
SP  - 245 - 259
PY  - 2023
AB  - Remodeling of synapses by microglia is essential for synaptic plasticity in the brain. However, during neuroinflammation and neurodegenerative diseases, microglia can induce excessive synaptic loss, although the precise underlying mechanisms are unknown. To directly observe microglia-synapse interactions under inflammatory conditions, we performed in vivo two-photon time-lapse imaging of microglia-synapse interactions after bacterial lipopolysaccharide administration to model systemic inflammation, or after inoculation of Alzheimer's disease (AD) brain extracts to model disease-associated neuroinflammatory microglial response. Both treatments prolonged microglia-neuron contacts, decreased basal surveillance of synapses and promoted synaptic remodeling in response to synaptic stress induced by focal single-synapse photodamage. Spine elimination correlated with the expression of microglial complement system/phagocytic proteins and the occurrence of synaptic filopodia. Microglia were observed contacting spines, then stretching and phagocytosing spine head filopodia. Thus, in response to inflammatory stimuli microglia exacerbated spine remodeling through prolonged microglial contact and elimination of spines 'tagged' by synaptic filopodia.
KW  - Humans
KW  - Microglia: metabolism
KW  - Tauopathies: metabolism
KW  - Alzheimer Disease: metabolism
KW  - Synapses: metabolism
KW  - Inflammation: metabolism
KW  - Alzheimer's disease (Other)
KW  - C1q (Other)
KW  - C3 (Other)
KW  - C3R (Other)
KW  - CD68 (Other)
KW  - Microglia (Other)
KW  - Spine elimination (Other)
KW  - Spine head filopodia (Other)
KW  - Spine turnover (Other)
KW  - Synapse (Other)
KW  - Synaptic remodeling (Other)
KW  - tau (Other)
LB  - PUB:(DE-HGF)16
C6  - pmid:36906076
DO  - DOI:10.1016/j.bbi.2023.02.023
UR  - https://pub.dzne.de/record/257592
ER  -