BACKGROUND Serine synthetic pathway plays an essential role in the development and function of the nervous system. This study investigated whether the serine synthetic pathway was affected by repeated volatile anesthetic exposure using C. elegans and its relationship with anesthesia-induced neurotoxicity. METHODS Synchronized worms were divided into two groups: the control and isoflurane groups. Worms in the isoflurane group were exposed to isoflurane for 1 h at each larval stage. The chemotaxis index was evaluated when they reached the young adult-stage in both groups. Also, RNA was extracted from the young adult-worms, and the expressions of C31C9.2, F26H9.5, and Y62E10 A.13 were evaluated using real-time polymerase chain reaction in both groups. At the same time, the l-serine level was measured. After phosphoserine phosphatase inhibitor - glycerophosphorylcholine (GPC) - and l-serine were treated, the change of chemotaxis index was determined. RESULTS In young adult worms exposed to isoflurane, the genetic expressions of C31C9.2, F26H9.5, and Y62E10 A.13 were decreased, and a significant decrease was shown in Y62E10 A.13. The serine level in worms was also lower in the isoflurane group than in the control group (5.13 ± 1.44 vs. 7.65 ± 0.81 pM, n = 5 in each group, p = 0.009). Exposure to GPC reduced the chemotaxis index to a similar degree as repeated isoflurane exposure (52.9% in GPC group vs 58.7% in the isoflurane group). The chemotaxis index (61.1%) was not decreased by repeated isoflurane anesthesia in GPC-treated worms. In this condition, the l-serine level was low similarly in both groups (5.22 ± 1.19 vs. 4.90 ± 1.36 pM, n = 5 in each group, p = 0.702). When l-serine was supplied to C. elegans, the deteriorated chemotaxis index by isoflurane exposure recovered (78.1% in the control group vs. 75.5% in the isoflurane group, p = 0.465). CONCLUSION Serine synthetic pathway was negatively affected in C. elegans by repeated isoflurane exposure. Y62E10 A.13, which corresponds to phosphoserine phosphatase, was mostly influenced, followed by low l-serine level. Supplementation with l-serine could restore the chemotaxis index.

中文翻译：

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秀丽隐杆线虫在发育期间反复异氟烷暴露对丝氨酸合成途径的影响。

背景技术丝氨酸合成途径在神经系统的发育和功能中起重要作用。这项研究调查丝氨酸合成途径是否受到线虫反复挥发性麻醉剂暴露的影响及其与麻醉药诱导的神经毒性的关系。方法同步蠕虫分为两组：对照组和异氟烷组。在每个幼虫阶段，将异氟烷组的蠕虫暴露于异氟烷1 h。当两组都达到年轻成人阶段时，对趋化性指数进行评估。同样，从幼虫中提取RNA，并使用实时聚合酶链反应评估两组中C31C9.2，F26H9.5和Y62E10 A.13的表达。同时，测量了l-丝氨酸水平。处理磷酸丝氨酸磷酸酶抑制剂-甘油磷酸胆碱（GPC）-和1-丝氨酸后，测定趋化性指数的变化。结果在暴露于异氟烷的年轻成年蠕虫中，C31C9.2，F26H9.5和Y62E10 A.13的基因表达降低，而在Y62E10 A.13中显示出显着降低。在异氟烷组中，蠕虫中的丝氨酸水平也低于对照组（5.13±1.44 vs. 7.65±0.81 pM，每组n = 5，p = 0.009）。接触GPC可使趋化指数降低至与重复异氟醚接触相似的程度（GPC组为52.9％，异氟烷组为58.7％）。在GPC处理的蠕虫中，反复进行异氟醚麻醉不会使趋化指数（61.1％）降低。在这种情况下，两组的l-丝氨酸水平相似（5.22±1.19 vs. 4.90±1.36 pM，每组n = 5，p = 0.702）。当将丝氨酸提供给秀丽隐杆线虫时，由于异氟烷暴露而降低的趋化性指数得以恢复（对照组为78.1％，而异氟烷组为75.5％，p = 0.465）。结论反复异氟烷暴露对秀丽隐杆线虫的丝氨酸合成途径有负面影响。对应于磷酸丝氨酸磷酸酶的Y62E10 A.13受到的影响最大，其次是较低的1-丝氨酸水平。补充左旋丝氨酸可以恢复趋化性指数。与磷酸丝氨酸磷酸酶相对应的蛋白主要受到影响，其后是低的1-丝氨酸水平。补充左旋丝氨酸可以恢复趋化性指数。与磷酸丝氨酸磷酸酶相对应的蛋白主要受到影响，其后是低的1-丝氨酸水平。补充左旋丝氨酸可以恢复趋化性指数。