The role of depolarizing activation of Na+-Ca2+ exchanger by oligodendrocyte progenitor cells in the effect of sevoflurane on myelination

Abstract

AimsThe aim of this study was to investigate the role of depolarizing activation of Na+-Ca2+ exchanger (NCX) by oligodendrocyte progenitor cells (OPC) in the effect of sevoflurane on myelination. Main methodsOn postnatal days 7, 8, and 9, mice were exposed to 3 % sevoflurane for 2 h per day. The proliferation, differentiation, and myelin sheath of OPC were observed with immunofluorescence, quantitative real-time polymerase chain reaction (QRT-PCR), and transmission electron microscopy (TEM) at various time points. The open field, Y maze, and new object recognition tests were used to measure spatial learning and memory. siRNA was used for the knockdown NCX1 in human OPC (HOPC) before sevoflurane exposure; the Transwell migration assay was used to measure cell migration ability and Fluo 4-AM was used to measure intracellular Ca2+ concentration. Key findingsPretreatment with an NCX inhibitor attenuated the proliferation and differentiation of OPC induced by sevoflurane and induced a remarkable increase in platelet-derived growth factor receptor-alpha (PDGFRα), 2, 3-cyclic nucleotide 3-phosphodiesterase (CNPase), oligodendrocyte transcription factor 2 (Olig2), and homeodomain protein NK2 homeobox 2 (NKX2.2) levels. Pretreatment with an NCX inhibitor alleviated the sevoflurane-induced myelination disorder and cognitive impairment. The decreased cell migration and increased intracellular Ca2+ concentration observed in the siRNA-negative control group was reversed in the sevoflurane plus siRNA-NCX1 group. SignificanceThis study suggests that repeated sevoflurane exposure in newborn mice leads to depolarization of OPC, which leads to Ca2+ influx through NCX and affects OPC proliferation, migration, differentiation, and myelination, ultimately leading to cognitive impairment.