The Anaesthetics Isoflurane and Xenon Reverse the Synaptotoxic Effects of Aβ<sub>1–42</sub> on Megf10-Dependent Astrocytic Synapse Elimination and Spine Density in Ex Vivo Hippocampal Brain Slices
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...
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MDPI AG
2023-01-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/2/912 |
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| author | Dai Shi Jaime K. Y. Wong Kaichuan Zhu Peter G. Noakes Gerhard Rammes |
| author_facet | Dai Shi Jaime K. Y. Wong Kaichuan Zhu Peter G. Noakes Gerhard Rammes |
| author_sort | Dai Shi |
| collection | DOAJ |
| description | 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 (Aβ<sub>1–42</sub>), 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 Aβ<sub>1–42</sub>, Iso or Xe and the combination of Aβ<sub>1–42</sub> 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. Aβ<sub>1–42</sub> 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 Aβ<sub>1–42</sub> 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 Aβ<sub>1–42</sub>-induced enhancement of synaptic elimination in ex vivo hippocampal brain slices, presumably through MEGF10 downregulation. |
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| spelling | doaj.art-f9f90fcfe14e4f20bf475209858386a52023-11-30T22:32:23ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-01-0124291210.3390/ijms24020912The Anaesthetics Isoflurane and Xenon Reverse the Synaptotoxic Effects of Aβ<sub>1–42</sub> on Megf10-Dependent Astrocytic Synapse Elimination and Spine Density in Ex Vivo Hippocampal Brain SlicesDai Shi0Jaime K. Y. Wong1Kaichuan Zhu2Peter G. Noakes3Gerhard Rammes4Department of Anesthesiology and Intensive Care, Klinikum Rechts der Isar, Ismaningerstraße 22, 81675 Munich, GermanySchool of Biomedical Sciences, The University of Queensland, St. Lucia, QLD 4072, AustraliaGerman Center for Neurodegenerative Diseases, Feodor-Lynen-Straße 23, 81377 Munich, GermanySchool of Biomedical Sciences, The University of Queensland, St. Lucia, QLD 4072, AustraliaDepartment of Anesthesiology and Intensive Care, Klinikum Rechts der Isar, Ismaningerstraße 22, 81675 Munich, GermanyIt 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 (Aβ<sub>1–42</sub>), 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 Aβ<sub>1–42</sub>, Iso or Xe and the combination of Aβ<sub>1–42</sub> 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. Aβ<sub>1–42</sub> 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 Aβ<sub>1–42</sub> 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 Aβ<sub>1–42</sub>-induced enhancement of synaptic elimination in ex vivo hippocampal brain slices, presumably through MEGF10 downregulation.https://www.mdpi.com/1422-0067/24/2/912Alzheimer’s diseasedendritic spine densityMEGF10astrocytessynapse eliminationphagocytosis |
| spellingShingle | Dai Shi Jaime K. Y. Wong Kaichuan Zhu Peter G. Noakes Gerhard Rammes The Anaesthetics Isoflurane and Xenon Reverse the Synaptotoxic Effects of Aβ<sub>1–42</sub> on Megf10-Dependent Astrocytic Synapse Elimination and Spine Density in Ex Vivo Hippocampal Brain Slices International Journal of Molecular Sciences Alzheimer’s disease dendritic spine density MEGF10 astrocytes synapse elimination phagocytosis |
| title | The Anaesthetics Isoflurane and Xenon Reverse the Synaptotoxic Effects of Aβ<sub>1–42</sub> on Megf10-Dependent Astrocytic Synapse Elimination and Spine Density in Ex Vivo Hippocampal Brain Slices |
| title_full | The Anaesthetics Isoflurane and Xenon Reverse the Synaptotoxic Effects of Aβ<sub>1–42</sub> on Megf10-Dependent Astrocytic Synapse Elimination and Spine Density in Ex Vivo Hippocampal Brain Slices |
| title_fullStr | The Anaesthetics Isoflurane and Xenon Reverse the Synaptotoxic Effects of Aβ<sub>1–42</sub> on Megf10-Dependent Astrocytic Synapse Elimination and Spine Density in Ex Vivo Hippocampal Brain Slices |
| title_full_unstemmed | The Anaesthetics Isoflurane and Xenon Reverse the Synaptotoxic Effects of Aβ<sub>1–42</sub> on Megf10-Dependent Astrocytic Synapse Elimination and Spine Density in Ex Vivo Hippocampal Brain Slices |
| title_short | The Anaesthetics Isoflurane and Xenon Reverse the Synaptotoxic Effects of Aβ<sub>1–42</sub> on Megf10-Dependent Astrocytic Synapse Elimination and Spine Density in Ex Vivo Hippocampal Brain Slices |
| title_sort | anaesthetics isoflurane and xenon reverse the synaptotoxic effects of aβ sub 1 42 sub on megf10 dependent astrocytic synapse elimination and spine density in ex vivo hippocampal brain slices |
| topic | Alzheimer’s disease dendritic spine density MEGF10 astrocytes synapse elimination phagocytosis |
| url | https://www.mdpi.com/1422-0067/24/2/912 |
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