| First Author | Shi D | Year | 2023 |
| Journal | Int J Mol Sci | Volume | 24 |
| Issue | 2 | PubMed ID | 36674434 |
| Mgi Jnum | J:332847 | Mgi Id | MGI:7430268 |
| Doi | 10.3390/ijms24020912 | Citation | Shi D, et al. (2023) The Anaesthetics Isoflurane and Xenon Reverse the Synaptotoxic Effects of Abeta(1-42) on Megf10-Dependent Astrocytic Synapse Elimination and Spine Density in Ex Vivo Hippocampal Brain Slices. Int J Mol Sci 24(2) |
| abstractText | 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 beta-amyloid peptide 1-42 (Abeta(1-42)), 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 Abeta(1-42), Iso or Xe and the combination of Abeta(1-42) 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. Abeta(1-42) 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 Abeta(1-42) 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 Abeta(1-42)-induced enhancement of synaptic elimination in ex vivo hippocampal brain slices, presumably through MEGF10 downregulation. |
