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

Autor:	Dai Shi, Jaime K. Y. Wong, Kaichuan Zhu, Peter G. Noakes, Gerhard Rammes
Jazyk:	angličtina
Rok vydání:	2023
Předmět:	Alzheimer’s disease dendritic spine density MEGF10 astrocytes synapse elimination phagocytosis pharmacology [Anesthetics Inhalation] metabolism [Amyloid beta-Peptides] metabolism [Hippocampus] Catalysis Inorganic Chemistry Mice pharmacology [Xenon] Animals metabolism [Peptide Fragments] Physical and Theoretical Chemistry Molecular Biology Spectroscopy metabolism [Astrocytes] Organic Chemistry General Medicine metabolism [Synapses] Article Alzheimer's disease Computer Science Applications ddc metabolism [Xenon] metabolism [Brain] ddc:540 pharmacology [Isoflurane] metabolism [Alzheimer Disease] metabolism [Membrane Proteins]
Zdroj:	International Journal of Molecular Sciences; Volume 24; Issue 2; Pages: 912 International journal of molecular sciences 24(2), 912 (2023). doi:10.3390/ijms24020912
ISSN:	1422-0067
DOI:	10.3390/ijms24020912
Popis:	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.
Databáze:	OpenAIRE
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