Journal Article

DZNE-2023-00167

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png 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.

Shi, D. ; Wong, J. K. Y. ; Zhu, K.DZNE* ; Noakes, P. G. ; Rammes, G.

2023
Molecular Diversity Preservation International Basel

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Please use a persistent id in citations: doi:10.3390/ijms24020912

Abstract: 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.

Keyword(s): Mice (MeSH) ; Animals (MeSH) ; Isoflurane: pharmacology (MeSH) ; Xenon: pharmacology (MeSH) ; Xenon: metabolism (MeSH) ; Astrocytes: metabolism (MeSH) ; Amyloid beta-Peptides: metabolism (MeSH) ; Brain: metabolism (MeSH) ; Hippocampus: metabolism (MeSH) ; Peptide Fragments: metabolism (MeSH) ; Alzheimer Disease: metabolism (MeSH) ; Anesthetics, Inhalation: pharmacology (MeSH) ; Synapses: metabolism (MeSH) ; Membrane Proteins: metabolism (MeSH) ; Alzheimer’s disease ; Alzheimer’s disease ; MEGF10 ; astrocytes ; dendritic spine density ; phagocytosis ; synapse elimination ; amyloid beta-protein (1-42) ; Isoflurane ; Xenon ; Amyloid beta-Peptides ; Peptide Fragments ; Anesthetics, Inhalation ; Megf10 protein, mouse ; Membrane Proteins

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Contributing Institute(s):

1. Translational Brain Research (AG Herms)

Research Program(s):

1. 352 - Disease Mechanisms (POF4-352) (POF4-352)

Appears in the scientific report 2023

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Database coverage:
; ; ; ; Article Processing Charges ; Clarivate Analytics Master Journal List ; Current Contents - Physical, Chemical and Earth Sciences ; DOAJ Seal ; Ebsco Academic Search ; Essential Science Indicators ; Fees ; IF >= 5 ; JCR ; PubMed Central ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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Linked articles:

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Journal Article (Erratum/Correction) Shi, D. ; Wong, J. K. Y. ; Zhu, K.DZNE* ; Noakes, P. G. ; Rammes, G.
Correction: Shi et al. 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. Int. J. Mol. Sci. 2023, 24, 912.
International journal of molecular sciences 26(18), 8797 (2025) [10.3390/ijms26188797]2025   Files  Fulltext by Pubmed Central BibTeX | EndNote: XML, Text | RIS

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