The Effects of Sevoflurane and Aß Interaction on CA1 Dendritic Spine Dynamics and MEGF10-Related Astrocytic Synapse Engulfment.

ABSTRACT

General anesthetics may accelerate the neuropathological changes related to Alzheimer's disease (AD), of which amyloid beta (Aß)-induced toxicity is one of the main causes. However, the interaction of general anesthetics with different Aß-isoforms remains unclear. In this study, we investigated the effects of sevoflurane (0.4 and 1.2 maximal alveolar concentration (MAC)) on four Aß species-induced changes on dendritic spine density (DSD) in hippocampal brain slices of Thy1-eGFP mice and multiple epidermal growth factor-like domains 10 (MEGF10)-related astrocyte-mediated synaptic engulfment in hippocampal brain slices of C57BL/6 mice. We found that both sevoflurane and Aß downregulated CA1-dendritic spines. Moreover, compared with either sevoflurane or Aß alone, pre-treatment with Aß isoforms followed by sevoflurane application in general further enhanced spine loss. This enhancement was related to MEGF10-related astrocyte-dependent synaptic engulfment, only in AßpE3 + 1.2 MAC sevoflurane and 3NTyrAß + 1.2 MAC sevoflurane condition. In addition, removal of sevoflurane alleviated spine loss in Aß + sevoflurane. In summary, these results suggest that both synapses and astrocytes are sensitive targets for sevoflurane; in the presence of 3NTyrAß, 1.2 MAC sevoflurane alleviated astrocyte-mediated synaptic engulfment and exerted a lasting effect on dendritic spine remodeling.