General anesthesia induces changes in dendritic spine number and synaptic transmission in developing mice. These changes are rather disturbing, as similar changes are seen in animal models of neurodevelopmental disorders. We previously suggested that mTor-dependent upregulation of mitochondrial function may be involved in such changes. To further understand the significance of mitochondrial changes after general anesthesia during neurodevelopment, we exposed young mice to 2.5 % sevoflurane for 2 h followed by injection of rotenone, a mitochondrial complex I inhibitor. In postnatal day 17 (PND17) mice, intraperitoneal injection of rotenone not only blocked sevoflurane-induced increases in mitochondrial function, it also prevented sevoflurane-induced changes in excitatory synaptic transmission. Interestingly, similar changes were not observed in younger, neonatal mice (PND7). We next assessed whether the mitochondrial unfolded protein response (UPR^mt) acted as a link between anesthetic exposure and mitochondrial function. Expression of UPR^mt proteins, which help maintain protein-folding homeostasis and increase mitochondrial function, was increased 6 h after sevoflurane exposure. Our results show that a single, brief sevoflurane exposure induces age-dependent changes in mitochondrial function that constitute an important mechanism for the increase in excitatory synaptic transmission in late postnatal mice, and also suggest mitochondria and UPR^mt as potential targets for preventing anesthesia toxicity.

全身麻醉诱导发育中小鼠的树突棘数量和突触传递发生变化。这些变化相当令人不安，因为在神经发育障碍的动物模型中可以看到类似的变化。我们以前认为 mTor 依赖的线粒体功能上调可能与这些变化有关。为了进一步了解神经发育过程中全身麻醉后线粒体变化的重要性，我们将幼鼠暴露于 2.5% 七氟醚 2 小时，然后注射鱼藤酮，一种线粒体复合物 I 抑制剂。在出生后第 17 天 (PND17) 小鼠中，腹腔注射鱼藤酮不仅阻止七氟醚诱导的线粒体功能增加，还阻止七氟醚诱导的兴奋性突触传递变化。有趣的是，在较年轻的新生小鼠 (PND7) 中未观察到类似的变化。我们接下来评估了线粒体未折叠蛋白反应（UPR^mt ) 充当麻醉剂暴露和线粒体功能之间的联系。七氟醚暴露后 6 小时，UPR ^mt蛋白的表达增加，有助于维持蛋白质折叠稳态和增加线粒体功能。我们的研究结果表明，单次、短暂的七氟醚暴露会诱导线粒体功能的年龄依赖性变化，这构成了出生后期小鼠兴奋性突触传递增加的重要机制，并且还表明线粒体和 UPR ^mt是预防麻醉毒性的潜在靶点。