%0 Conference Paper
%A Chamoun, Miriam
%A Nebeling, Felix
%A Schneider, J
%A Steffen, Julia
%A Gu, Ligang
%A Fuhrmann, Martin
%T Microglia synapse interaction precedes synapse elimination in mouse models of AD
%J Glia
%V 65
%N S1
%@ 0894-1491
%M DZNE-2020-00698
%P E290
%D 2017
%X Microglia are actively surveying the brain parenchyma by protracting and retracting their fine processes. They physically interact with neurons and their synapses and have been shown to influence the morphology of dendritic spines dependent on the contact rate under normal physiological conditions. Under neurodegenerative disease conditions like Alzheimer¶s disease (AD), microglia mediate early synapse loss via the complement system or neuron loss dependent on the fractalkine receptor (CX3CR1). It remains unresolved whether microglia contribute to synapse loss during late disease stages, whether that changes contact rates or involves neuron microglia communication via the CX3CR1 receptor. To address these open questions, we carried out time-lapse two-photon in vivo imaging in the hippocampus and cortex of two different mouse models of AD, the APP/PS1 and the 3xTg-AD model. We analyzed dendritic spine loss in relation to microglia contact rates of dendritic spines and with respect to CX3CR1-deficiency under advanced AD-like conditions. We found increased turnover and loss of dendritic spines under AD-like conditions. Furthermore, spine loss in proximity to Aȕ-plaques was ameliorated in CX3CR1-deficient APP/PS1 mice. Surprisingly, the microglia contact rates of dendritic spines before elimination were significantly reduced dependent on CX3CR1-deficiency. Reduced microglia contact rates dependent on CX3CR1-deficiency were consistently found in APP/PS1 and 3xTg-AD mice similarly in the cortex and hippocampus. These data indicate that microglia mediate synapse loss via elevated physical synapse interactions dependent on the CX3CR1 receptor under advanced AD-like conditions. 
%B GLIA Edinburgh 2017
%C 8 Jul 2017 - 11 Jul 2017, Edinburgh (Scotland)
Y2 8 Jul 2017 - 11 Jul 2017
M2 Edinburgh, Scotland
%F PUB:(DE-HGF)1 ; PUB:(DE-HGF)16
%9 AbstractJournal Article
%U https://pub.dzne.de/record/145342