The effect of repeated isoflurane exposure on serine synthesis pathway during the developmental period in Caenorhabditis elegans.

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.