Early-life multiple anesthetics exposure causes neurotoxicity and hence cognitive dysfunction on developing brain. However, the effects of early-life multiple sevoflurane exposures on emotional changes, especially upon stress, are far beyond understood. In young male C57BL6/J mice, the present study showed that 3% sevoflurane inhalation for 2 h in three consecutive days did not influence anxiety-like behaviors as measured by open field test, light dark transition, and elevated plus maze test. In addition, foot shocks stress induced both the short- and long-term anxiety-like behaviors. However, triple sevoflurane exposures ameliorated the long-term anxiety-like behaviors induced by the foot shocks. In parallel, foot shocks stress upregulated the expression of phosphorylated extracellular signal-regulated kinase (p-ERK) and brain-derived neurotrophic factor precursor (proBDNF) in the anterior cingulate cortex (ACC), which were significantly inhibited by triple sevoflurane exposures. Immunofluorescence further indicated that the increased p-ERK was mainly expressed in the proBDNF-positive staining cells. Intra-ACC injection of recombinant proBDNF protein upregulated the p-ERK expression and blocked the anxiolytic effect of sevoflurane exposure on long-term anxiety-like behaviors. Therefore, our study demonstrated that multiple sevoflurane exposures alleviate long-term anxiety-like behaviors upon acute stress in young mice by inhibiting proBDNF-ERK signaling in the ACC.

中文翻译：

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生命早期多次接触七氟醚可通过 proBDNF/ERK 途径减轻小鼠的长期焦虑样行为。

早年接触多种麻醉剂会导致神经毒性，从而导致发育中的大脑出现认知功能障碍。然而，早年多次接触七氟醚对情绪变化的影响，尤其是对压力的影响，远远无法理解。在年轻的雄性 C57BL6/J 小鼠中，本研究表明，连续三天吸入 3% 七氟醚 2 小时不会影响通过开放场试验、浅暗过渡和高架十字迷宫试验测量的焦虑样行为。此外，足部电击压力会诱发短期和长期的类似焦虑的行为。然而，三重七氟醚暴露改善了由足部电击引起的长期焦虑样行为。在平行下，足部电击应激上调了前扣带回皮层 (ACC) 中磷酸化细胞外信号调节激酶 (p-ERK) 和脑源性神经营养因子前体 (proBDNF) 的表达，而三重七氟醚暴露显着抑制了这些表达。免疫荧光进一步表明增加的p-ERK主要在proBDNF阳性染色细胞中表达。ACC内注射重组proBDNF蛋白上调p-ERK表达并阻断七氟醚暴露对长期焦虑样行为的抗焦虑作用。因此，我们的研究表明，多次接触七氟醚可通过抑制 ACC 中的 proBDNF-ERK 信号传导来缓解年轻小鼠急性应激时的长期焦虑样行为。三重七氟醚暴露显着抑制。免疫荧光进一步表明增加的p-ERK主要在proBDNF阳性染色细胞中表达。ACC内注射重组proBDNF蛋白上调p-ERK表达并阻断七氟醚暴露对长期焦虑样行为的抗焦虑作用。因此，我们的研究表明，多次接触七氟醚可通过抑制 ACC 中的 proBDNF-ERK 信号传导来缓解年轻小鼠急性应激时的长期焦虑样行为。三重七氟醚暴露显着抑制。免疫荧光进一步表明增加的p-ERK主要在proBDNF阳性染色细胞中表达。ACC内注射重组proBDNF蛋白上调p-ERK表达并阻断七氟醚暴露对长期焦虑样行为的抗焦虑作用。因此，我们的研究表明，多次接触七氟醚可通过抑制 ACC 中的 proBDNF-ERK 信号传导来缓解年轻小鼠急性应激时的长期焦虑样行为。ACC内注射重组proBDNF蛋白上调p-ERK表达并阻断七氟醚暴露对长期焦虑样行为的抗焦虑作用。因此，我们的研究表明，多次接触七氟醚可通过抑制 ACC 中的 proBDNF-ERK 信号传导来缓解年轻小鼠急性应激时的长期焦虑样行为。ACC内注射重组proBDNF蛋白上调p-ERK表达并阻断七氟醚暴露对长期焦虑样行为的抗焦虑作用。因此，我们的研究表明，多次接触七氟醚可通过抑制 ACC 中的 proBDNF-ERK 信号传导来缓解年轻小鼠急性应激时的长期焦虑样行为。