PDF(Pubmed)
Abstract：
General anesthetics may accelerate the neuropathological changes related to Alzheimer\'s disease (AD), of which amyloid beta (Aβ)-induced toxicity is one of the main causes. However, the interaction of general anesthetics with different Aβ-isoforms remains unclear. In this study, we investigated the effects of sevoflurane (0.4 and 1.2 maximal alveolar concentration (MAC)) on four Aβ 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 Aβ downregulated CA1-dendritic spines. Moreover, compared with either sevoflurane or Aβ alone, pre-treatment with Aβ isoforms followed by sevoflurane application in general further enhanced spine loss. This enhancement was related to MEGF10-related astrocyte-dependent synaptic engulfment, only in AβpE3 + 1.2 MAC sevoflurane and 3NTyrAβ + 1.2 MAC sevoflurane condition. In addition, removal of sevoflurane alleviated spine loss in Aβ + sevoflurane. In summary, these results suggest that both synapses and astrocytes are sensitive targets for sevoflurane; in the presence of 3NTyrAβ, 1.2 MAC sevoflurane alleviated astrocyte-mediated synaptic engulfment and exerted a lasting effect on dendritic spine remodeling.
摘要：
全身麻醉药可能加速与阿尔茨海默病(AD)相关的神经病理学改变,其中淀粉样蛋白β（Aβ）诱导的毒性是主要原因之一。然而,全身麻醉药与不同Aβ亚型的相互作用尚不清楚.在这项研究中,我们研究了七氟醚（0.4和1.2最大肺泡浓度（MAC））对4种Aβ物种诱导的Thy1-eGFP小鼠海马脑片树突棘密度（DSD）变化的影响，以及C57BL/6小鼠海马脑片中多个表皮生长因子样结构域10（MEGF10）相关的星形胶质细胞介导的突触吞噬。我们发现七氟醚和Aβ均下调CA1-树突棘。此外，与七氟醚或Aβ单独相比，用Aβ同工型进行预处理，然后应用七氟醚，通常会进一步增强脊柱丢失。这种增强与MEGF10相关的星形胶质细胞依赖性突触吞噬有关，仅在AβpE3+1.2MAC七氟醚和3NTyrAβ+1.2MAC七氟醚条件下。此外,七氟烷切除减轻了Aβ+七氟烷的脊柱丢失。总之,这些结果表明，突触和星形胶质细胞都是七氟醚的敏感靶标；在存在3NTyrAβ的情况下，1.2MAC七氟醚减轻星形胶质细胞介导的突触吞噬，并对树突棘重塑产生持久影响。
