Journal Article

DZNE-2023-00468

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Real-time mechanisms of exacerbated synaptic remodeling by microglia in acute models of systemic inflammation and tauopathy.

Cangalaya, C. (First author)DZNE* ; Wegmann, S.DZNE* ; Sun, W.DZNE* ; Diez, L.DZNE* ; Gottfried, A. ; Richter, K. ; Stoyanov, S.DZNE* ; Pakan, J.DZNE* ; Fischer, K.-D. ; Dityatev, A. (Last author)DZNE*

2023
Academic Press Orlando, Fla.

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Please use a persistent id in citations: doi:10.1016/j.bbi.2023.02.023

Abstract: 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.

Keyword(s): Humans (MeSH) ; Microglia: metabolism (MeSH) ; Tauopathies: metabolism (MeSH) ; Alzheimer Disease: metabolism (MeSH) ; Synapses: metabolism (MeSH) ; Inflammation: metabolism (MeSH) ; Alzheimer's disease ; C1q ; C3 ; C3R ; CD68 ; Microglia ; Spine elimination ; Spine head filopodia ; Spine turnover ; Synapse ; Synaptic remodeling ; tau

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Contributing Institute(s):

1. Molecular Neuroplasticity (AG Dityatev)
2. Protein Actions in Neurodegeneration (AG Wegmann)

Research Program(s):

1. 351 - Brain Function (POF4-351) (POF4-351)
2. 352 - Disease Mechanisms (POF4-352) (POF4-352)

Appears in the scientific report 2023

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Database coverage:
; ; ; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 15 ; JCR ; Nationallizenz ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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