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000257592 1001_ $$0P:(DE-2719)9001455$$aCangalaya, Carla$$b0$$eFirst author$$udzne
000257592 245__ $$aReal-time mechanisms of exacerbated synaptic remodeling by microglia in acute models of systemic inflammation and tauopathy.
000257592 260__ $$aOrlando, Fla.$$bAcademic Press$$c2023
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000257592 520__ $$aRemodeling 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.
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000257592 650_7 $$2Other$$aAlzheimer's disease
000257592 650_7 $$2Other$$aC1q
000257592 650_7 $$2Other$$aC3
000257592 650_7 $$2Other$$aC3R
000257592 650_7 $$2Other$$aCD68
000257592 650_7 $$2Other$$aMicroglia
000257592 650_7 $$2Other$$aSpine elimination
000257592 650_7 $$2Other$$aSpine head filopodia
000257592 650_7 $$2Other$$aSpine turnover
000257592 650_7 $$2Other$$aSynapse
000257592 650_7 $$2Other$$aSynaptic remodeling
000257592 650_7 $$2Other$$atau
000257592 650_2 $$2MeSH$$aHumans
000257592 650_2 $$2MeSH$$aMicroglia: metabolism
000257592 650_2 $$2MeSH$$aTauopathies: metabolism
000257592 650_2 $$2MeSH$$aAlzheimer Disease: metabolism
000257592 650_2 $$2MeSH$$aSynapses: metabolism
000257592 650_2 $$2MeSH$$aInflammation: metabolism
000257592 7001_ $$0P:(DE-2719)2812695$$aWegmann, Susanne$$b1$$udzne
000257592 7001_ $$0P:(DE-2719)2811509$$aSun, Weilun$$b2$$udzne
000257592 7001_ $$0P:(DE-2719)2812826$$aDiez, Lisa$$b3$$udzne
000257592 7001_ $$aGottfried, Anna$$b4
000257592 7001_ $$aRichter, Karin$$b5
000257592 7001_ $$0P:(DE-2719)2809920$$aStoyanov, Stoyan$$b6$$udzne
000257592 7001_ $$0P:(DE-2719)2813669$$aPakan, Janelle$$b7$$udzne
000257592 7001_ $$aFischer, Klaus-Dieter$$b8
000257592 7001_ $$0P:(DE-2719)2810577$$aDityatev, Alexander$$b9$$eLast author$$udzne
000257592 773__ $$0PERI:(DE-600)1462491-6$$a10.1016/j.bbi.2023.02.023$$gVol. 110, p. 245 - 259$$p245 - 259$$tBrain, behavior and immunity$$v110$$x0889-1591$$y2023
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