000194980 001__ 194980 000194980 005__ 20240403131747.0 000194980 0247_ $$2doi$$a10.3390/ijms24020912 000194980 0247_ $$2pmid$$apmid:36674434 000194980 0247_ $$2pmc$$apmc:PMC9861496 000194980 0247_ $$2ISSN$$a1422-0067 000194980 0247_ $$2ISSN$$a1661-6596 000194980 0247_ $$2altmetric$$aaltmetric:141630626 000194980 037__ $$aDZNE-2023-00167 000194980 041__ $$aEnglish 000194980 082__ $$a540 000194980 1001_ $$aShi, Dai$$b0 000194980 245__ $$aThe 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. 000194980 260__ $$aBasel$$bMolecular Diversity Preservation International$$c2023 000194980 3367_ $$2DRIVER$$aarticle 000194980 3367_ $$2DataCite$$aOutput Types/Journal article 000194980 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article$$bjournal$$mjournal$$s1711378376_22712 000194980 3367_ $$2BibTeX$$aARTICLE 000194980 3367_ $$2ORCID$$aJOURNAL_ARTICLE 000194980 3367_ $$00$$2EndNote$$aJournal Article 000194980 520__ $$aIt has been hypothesised that inhalational anaesthetics such as isoflurane (Iso) may trigger the pathogenesis of Alzheimer's disease (AD), while the gaseous anaesthetic xenon (Xe) exhibits many features of a putative neuroprotective agent. Loss of synapses is regarded as one key cause of dementia in AD. Multiple EGF-like domains 10 (MEGF10) is one of the phagocytic receptors which assists the elimination of synapses by astrocytes. Here, we investigated how β-amyloid peptide 1-42 (Aβ1-42), Iso and Xe interact with MEGF10-dependent synapse elimination. Murine cultured astrocytes as well as cortical and hippocampal ex vivo brain slices were treated with either Aβ1-42, Iso or Xe and the combination of Aβ1-42 with either Iso or Xe. We quantified MEGF10 expression in astrocytes and dendritic spine density (DSD) in slices. In brain slices of wild type and AAV-induced MEGF10 knock-down mice, antibodies against astrocytes (GFAP), pre- (synaptophysin) and postsynaptic (PSD95) components were used for co-localization analyses by means of immunofluorescence-imaging and 3D rendering techniques. Aβ1-42 elevated pre- and postsynaptic components inside astrocytes and decreased DSD. The combined application with either Iso or Xe reversed these effects. In the presence of Aβ1-42 both anaesthetics decreased MEGF10 expression. AAV-induced knock-down of MEGF10 reduced the pre- and postsynaptic marker inside astrocytes. The presented data suggest Iso and Xe are able to reverse the Aβ1-42-induced enhancement of synaptic elimination in ex vivo hippocampal brain slices, presumably through MEGF10 downregulation. 000194980 536__ $$0G:(DE-HGF)POF4-352$$a352 - Disease Mechanisms (POF4-352)$$cPOF4-352$$fPOF IV$$x0 000194980 588__ $$aDataset connected to CrossRef, PubMed, , Journals: pub.dzne.de 000194980 650_7 $$2Other$$aAlzheimer’s disease 000194980 650_7 $$2Other$$aAlzheimer’s disease 000194980 650_7 $$2Other$$aMEGF10 000194980 650_7 $$2Other$$aastrocytes 000194980 650_7 $$2Other$$adendritic spine density 000194980 650_7 $$2Other$$aphagocytosis 000194980 650_7 $$2Other$$asynapse elimination 000194980 650_7 $$2NLM Chemicals$$aamyloid beta-protein (1-42) 000194980 650_7 $$0CYS9AKD70P$$2NLM Chemicals$$aIsoflurane 000194980 650_7 $$03H3U766W84$$2NLM Chemicals$$aXenon 000194980 650_7 $$2NLM Chemicals$$aAmyloid beta-Peptides 000194980 650_7 $$2NLM Chemicals$$aPeptide Fragments 000194980 650_7 $$2NLM Chemicals$$aAnesthetics, Inhalation 000194980 650_7 $$2NLM Chemicals$$aMegf10 protein, mouse 000194980 650_7 $$2NLM Chemicals$$aMembrane Proteins 000194980 650_2 $$2MeSH$$aMice 000194980 650_2 $$2MeSH$$aAnimals 000194980 650_2 $$2MeSH$$aIsoflurane: pharmacology 000194980 650_2 $$2MeSH$$aXenon: pharmacology 000194980 650_2 $$2MeSH$$aXenon: metabolism 000194980 650_2 $$2MeSH$$aAstrocytes: metabolism 000194980 650_2 $$2MeSH$$aAmyloid beta-Peptides: metabolism 000194980 650_2 $$2MeSH$$aBrain: metabolism 000194980 650_2 $$2MeSH$$aHippocampus: metabolism 000194980 650_2 $$2MeSH$$aPeptide Fragments: metabolism 000194980 650_2 $$2MeSH$$aAlzheimer Disease: metabolism 000194980 650_2 $$2MeSH$$aAnesthetics, Inhalation: pharmacology 000194980 650_2 $$2MeSH$$aSynapses: metabolism 000194980 650_2 $$2MeSH$$aMembrane Proteins: metabolism 000194980 7001_ $$aWong, Jaime K Y$$b1 000194980 7001_ $$0P:(DE-2719)2811999$$aZhu, Kaichuan$$b2$$udzne 000194980 7001_ $$00000-0001-9821-8478$$aNoakes, Peter G$$b3 000194980 7001_ $$aRammes, Gerhard$$b4 000194980 770__ $$aAdvance on the Research of Alzheimer's Disease 000194980 773__ $$0PERI:(DE-600)2019364-6$$a10.3390/ijms24020912$$gVol. 24, no. 2, p. 912 -$$n2$$p912$$tInternational journal of molecular sciences$$v24$$x1422-0067$$y2023 000194980 8564_ $$uhttps://pub.dzne.de/record/194980/files/DZNE-2023-00167.pdf$$yOpenAccess 000194980 8564_ $$uhttps://pub.dzne.de/record/194980/files/DZNE-2023-00167.pdf?subformat=pdfa$$xpdfa$$yOpenAccess 000194980 909CO $$ooai:pub.dzne.de:194980$$pdnbdelivery$$pdriver$$pVDB$$popen_access$$popenaire 000194980 9101_ $$0I:(DE-588)1065079516$$6P:(DE-2719)2811999$$aDeutsches Zentrum für Neurodegenerative Erkrankungen$$b2$$kDZNE 000194980 9131_ $$0G:(DE-HGF)POF4-352$$1G:(DE-HGF)POF4-350$$2G:(DE-HGF)POF4-300$$3G:(DE-HGF)POF4$$4G:(DE-HGF)POF$$aDE-HGF$$bGesundheit$$lNeurodegenerative Diseases$$vDisease Mechanisms$$x0 000194980 9141_ $$y2023 000194980 915__ $$0StatID:(DE-HGF)0200$$2StatID$$aDBCoverage$$bSCOPUS$$d2023-08-25 000194980 915__ $$0LIC:(DE-HGF)CCBYNV$$2V:(DE-HGF)$$aCreative Commons Attribution CC BY (No Version)$$bDOAJ$$d2022-09-04T08:27:04Z 000194980 915__ $$0StatID:(DE-HGF)0600$$2StatID$$aDBCoverage$$bEbsco Academic Search$$d2023-08-25 000194980 915__ $$0StatID:(DE-HGF)0199$$2StatID$$aDBCoverage$$bClarivate Analytics Master Journal List$$d2023-08-25 000194980 915__ $$0StatID:(DE-HGF)0100$$2StatID$$aJCR$$bINT J MOL SCI : 2022$$d2023-08-25 000194980 915__ $$0StatID:(DE-HGF)9905$$2StatID$$aIF >= 5$$bINT J MOL SCI : 2022$$d2023-08-25 000194980 915__ $$0StatID:(DE-HGF)0501$$2StatID$$aDBCoverage$$bDOAJ Seal$$d2023-07-07T16:31:47Z 000194980 915__ $$0StatID:(DE-HGF)0113$$2StatID$$aWoS$$bScience Citation Index Expanded$$d2022-11-25 000194980 915__ $$0StatID:(DE-HGF)0500$$2StatID$$aDBCoverage$$bDOAJ$$d2023-07-07T16:31:47Z 000194980 915__ $$0StatID:(DE-HGF)0300$$2StatID$$aDBCoverage$$bMedline$$d2023-08-25 000194980 915__ $$0StatID:(DE-HGF)0150$$2StatID$$aDBCoverage$$bWeb of Science Core Collection$$d2023-08-25 000194980 915__ $$0StatID:(DE-HGF)0510$$2StatID$$aOpenAccess 000194980 915__ $$0StatID:(DE-HGF)0030$$2StatID$$aPeer Review$$bASC$$d2023-08-25 000194980 915__ $$0StatID:(DE-HGF)0561$$2StatID$$aArticle Processing Charges$$d2022-11-25 000194980 915__ $$0StatID:(DE-HGF)1150$$2StatID$$aDBCoverage$$bCurrent Contents - Physical, Chemical and Earth Sciences$$d2023-08-25 000194980 915__ $$0StatID:(DE-HGF)0160$$2StatID$$aDBCoverage$$bEssential Science Indicators$$d2022-11-25 000194980 915__ $$0StatID:(DE-HGF)0320$$2StatID$$aDBCoverage$$bPubMed Central$$d2023-08-25 000194980 915__ $$0StatID:(DE-HGF)0700$$2StatID$$aFees$$d2022-11-25 000194980 915__ $$0StatID:(DE-HGF)0030$$2StatID$$aPeer Review$$bDOAJ : Anonymous peer review$$d2023-07-07T16:31:47Z 000194980 9201_ $$0I:(DE-2719)1110001$$kAG Herms$$lTranslational Brain Research$$x0 000194980 980__ $$ajournal 000194980 980__ $$aVDB 000194980 980__ $$aUNRESTRICTED 000194980 980__ $$aI:(DE-2719)1110001 000194980 9801_ $$aFullTexts