Abstract
BackgroundCurrently, numerous animal studies have shown that exposure to commonly used general anesthetics during pregnancy may cause neurocognitive impairment in the offspring. Reportedly, exposure to sevoflurane during mid-trimester of pregnancy can inhibit proliferation of neural stem cells (NSCs) and lead to early apoptosis. Whether exposure to sevoflurane during pregnancy affects the differentiation of NSCs remains unclear.MethodsIn the present study, pregnant rats were exposed to 3% sevoflurane once for 2 h on gestational day 14 (G14) or 3 times for 2 h on G13, G14, and G15. Next, the differentiation of NSCs was measured using neuron marker β-tubulin III and astrocyte marker glial fibrillary acidic protein (GFAP) in fetal brain tissues 24 h and 72 h after anesthesia and in hippocampus on postnatal day 28. Primary cultured rat NSCs were exposed to 4.1% sevoflurane to explore the mechanism.ResultsThe results showed that during mid-trimester, multiple exposures to sevoflurane can cause premature differentiation of NSCs in developing brains of offspring and lead to long-term neuron reduction and astrocyte proliferation in hippocampus. The data from the present study indicated that repeated exposure to sevoflurane downregulated atrophin-1 (ATN1) expression and caused early differentiation of NSCs. Overexpression of ATN1 via lentivirus transfection attenuated the influence of sevoflurane. Using dual luciferase assay, ATN1 was found to be a target gene of microRNA-410-3p (miR-410-3p). MiR-410-3p suppression via lentivirus transfection recovered the ATN1 expression and differentiation of NSCs.ConclusionsThe results from the present study demonstrated that repeated exposure to sevoflurane leads to early differentiation of NSCs and long-term effects via the miR-410-3p/ATN1 pathway.
Highlights
Numerous animal studies have shown that exposure to commonly used general anesthetics during pregnancy may cause neurocognitive impairment in the offspring
To induce Neural stem cell (NSC) differentiation, rat NSCs were digested into single cells and plated onto plates pre-coated with 0.25% poly-Dlysine (P6409; Sigma-Aldrich) using differentiation medium of Dulbecco’s modified Eagle’s medium (DMEM)/F12 supplemented with 2% B27 without vitamin A, 1% fetal bovine serum (FBS, 10100139; Gibco), and 1% penicillin-streptomycin
Observation under microscope showed that NSCs grew in a typical round shape (Fig. 1a), which was confirmed using immunofluorescence with the NSC marker nestin and Sex-determining region Y box 2 (SOX2)(Fig. 1b)
Summary
Numerous animal studies have shown that exposure to commonly used general anesthetics during pregnancy may cause neurocognitive impairment in the offspring. Exposure to sevoflurane during mid-trimester of pregnancy can inhibit proliferation of neural stem cells (NSCs) and lead to early apoptosis. Whether exposure to sevoflurane during pregnancy affects the differentiation of NSCs remains unclear. Numerous animal studies have shown that exposure to anesthesia drugs can lead to long-term neurocognitive impairment in the developing brain. The results showed that after sevoflurane exposure, the atrophin-1 (ATN1) level was significantly decreased. In most of the previous ATN1 expression studies [10, 11], the focus was on DRPLA. In the present study, whether sevoflurane could affect NSC differentiation by changing the expression of ATN1 was investigated
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