Role of D-serine in nerve cell apoptosis induced by multiple exposures to sevoflurane anesthesia in newborn mice: the relationship with GSK-3β

Abstract

Objective To evaluate the role of D-serine in nerve cell apoptosis induced by multiple exposures to sevoflurane anesthesia in newborn mice and its relationship with glycogen synthase kinase-3 beta (GSK-3β). Methods Thirty healthy male C57B/L6 mice, aged 6 days, weighing 3.5-4.5 g, were divided into 3 groups (n=10 each) using a random number table: control group (group C), multiple exposures to sevoflurane anesthesia group (group S) and D-serine group (group D). On postnatal days 6, 7 and 8, 3% sevoflurane in 30% oxygen was inhaled for 2 h starting from 10: 00 daily, and normal saline 0.1 ml and D-serine 500 mg/kg were intraperitoneally injected at 30 min before inhalation in S and D groups, respectively.In group C, 30% oxygen was inhaled for 2 h starting from 10: 00 daily, and normal saline 0.1 ml was intraperitoneally injected at 30 min before inhalation.The animals were sacrificed after the end of oxygen or sevoflurane inhalation on postnatal day 8, and the brains were removed for determination of the expression of phosphorylated GSK-3β (pGSK-3β) and activated caspase-3 in brain tissues by Western blot. Results Compared with group C, the expression of pGSK-3β in brain tissues was significantly down-regulated, and the expression of activated caspase-3 in brain tissues was up-regulated in group S (P 0.05). Compared with group S, the expression of pGSK-3β in brain tissues was significantly up-regulated, and the expression of activated caspase-3 in brain tissues was down-regulated in group D (P<0.05). Conclusion D-serine is involved in the nerve cell apoptosis induced by multiple exposures to sevoflurane anesthesia through inhibiting the activation of GSK-3β in newborn mice. Key words: Serine; Anesthetics, inhalation; Apoptosis; Infant, newborn; Glycogen synthase kinase 3