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@ARTICLE{Shi:194980,
      author       = {Shi, Dai and Wong, Jaime K Y and Zhu, Kaichuan and Noakes,
                      Peter G and Rammes, Gerhard},
      title        = {{T}he {A}naesthetics {I}soflurane and {X}enon {R}everse the
                      {S}ynaptotoxic {E}ffects of {A}β1-42 on
                      {M}egf10-{D}ependent {A}strocytic {S}ynapse {E}limination
                      and {S}pine {D}ensity in {E}x {V}ivo {H}ippocampal {B}rain
                      {S}lices.},
      journal      = {International journal of molecular sciences},
      volume       = {24},
      number       = {2},
      issn         = {1422-0067},
      address      = {Basel},
      publisher    = {Molecular Diversity Preservation International},
      reportid     = {DZNE-2023-00167},
      pages        = {912},
      year         = {2023},
      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.},
      keywords     = {Mice / Animals / Isoflurane: pharmacology / Xenon:
                      pharmacology / Xenon: metabolism / Astrocytes: metabolism /
                      Amyloid beta-Peptides: metabolism / Brain: metabolism /
                      Hippocampus: metabolism / Peptide Fragments: metabolism /
                      Alzheimer Disease: metabolism / Anesthetics, Inhalation:
                      pharmacology / Synapses: metabolism / Membrane Proteins:
                      metabolism / Alzheimer’s disease (Other) / Alzheimer’s
                      disease (Other) / MEGF10 (Other) / astrocytes (Other) /
                      dendritic spine density (Other) / phagocytosis (Other) /
                      synapse elimination (Other) / amyloid beta-protein (1-42)
                      (NLM Chemicals) / Isoflurane (NLM Chemicals) / Xenon (NLM
                      Chemicals) / Amyloid beta-Peptides (NLM Chemicals) / Peptide
                      Fragments (NLM Chemicals) / Anesthetics, Inhalation (NLM
                      Chemicals) / Megf10 protein, mouse (NLM Chemicals) /
                      Membrane Proteins (NLM Chemicals)},
      cin          = {AG Herms},
      ddc          = {540},
      cid          = {I:(DE-2719)1110001},
      pnm          = {352 - Disease Mechanisms (POF4-352)},
      pid          = {G:(DE-HGF)POF4-352},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:36674434},
      pmc          = {pmc:PMC9861496},
      doi          = {10.3390/ijms24020912},
      url          = {https://pub.dzne.de/record/194980},
}