%0 Journal Article
%A Shi, Dai
%A Wong, Jaime K Y
%A Zhu, Kaichuan
%A Noakes, Peter G
%A Rammes, Gerhard
%T The Anaesthetics Isoflurane and Xenon Reverse the Synaptotoxic Effects of Aβ1-42 on Megf10-Dependent Astrocytic Synapse Elimination and Spine Density in Ex Vivo Hippocampal Brain Slices.
%J International journal of molecular sciences
%V 24
%N 2
%@ 1422-0067
%C Basel
%I Molecular Diversity Preservation International
%M DZNE-2023-00167
%P 912
%D 2023
%X It has been hypothesised that inhalational anaesthetics such as isoflurane (Iso) may trigger the pathogenesis of Alzheimer's disease (AD), while the gaseous anaesthetic xenon (Xe) exhibits many features of a putative neuroprotective agent. Loss of synapses is regarded as one key cause of dementia in AD. Multiple EGF-like domains 10 (MEGF10) is one of the phagocytic receptors which assists the elimination of synapses by astrocytes. Here, we investigated how β-amyloid peptide 1-42 (Aβ1-42), Iso and Xe interact with MEGF10-dependent synapse elimination. Murine cultured astrocytes as well as cortical and hippocampal ex vivo brain slices were treated with either Aβ1-42, Iso or Xe and the combination of Aβ1-42 with either Iso or Xe. We quantified MEGF10 expression in astrocytes and dendritic spine density (DSD) in slices. In brain slices of wild type and AAV-induced MEGF10 knock-down mice, antibodies against astrocytes (GFAP), pre- (synaptophysin) and postsynaptic (PSD95) components were used for co-localization analyses by means of immunofluorescence-imaging and 3D rendering techniques. Aβ1-42 elevated pre- and postsynaptic components inside astrocytes and decreased DSD. The combined application with either Iso or Xe reversed these effects. In the presence of Aβ1-42 both anaesthetics decreased MEGF10 expression. AAV-induced knock-down of MEGF10 reduced the pre- and postsynaptic marker inside astrocytes. The presented data suggest Iso and Xe are able to reverse the Aβ1-42-induced enhancement of synaptic elimination in ex vivo hippocampal brain slices, presumably through MEGF10 downregulation.
%K Mice
%K Animals
%K Isoflurane: pharmacology
%K Xenon: pharmacology
%K Xenon: metabolism
%K Astrocytes: metabolism
%K Amyloid beta-Peptides: metabolism
%K Brain: metabolism
%K Hippocampus: metabolism
%K Peptide Fragments: metabolism
%K Alzheimer Disease: metabolism
%K Anesthetics, Inhalation: pharmacology
%K Synapses: metabolism
%K Membrane Proteins: metabolism
%K Alzheimer’s disease (Other)
%K Alzheimer’s disease (Other)
%K MEGF10 (Other)
%K astrocytes (Other)
%K dendritic spine density (Other)
%K phagocytosis (Other)
%K synapse elimination (Other)
%K amyloid beta-protein (1-42) (NLM Chemicals)
%K Isoflurane (NLM Chemicals)
%K Xenon (NLM Chemicals)
%K Amyloid beta-Peptides (NLM Chemicals)
%K Peptide Fragments (NLM Chemicals)
%K Anesthetics, Inhalation (NLM Chemicals)
%K Megf10 protein, mouse (NLM Chemicals)
%K Membrane Proteins (NLM Chemicals)
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:36674434
%2 pmc:PMC9861496
%R 10.3390/ijms24020912
%U https://pub.dzne.de/record/194980