Maternal sevoflurane exposure affects differentiation of hippocampal neural stem cells by regulating miR-410-3p and ATN1
- PDF / 5,884,909 Bytes
- 12 Pages / 595.276 x 790.866 pts Page_size
- 81 Downloads / 167 Views
(2020) 11:423
RESEARCH
Open Access
Maternal sevoflurane exposure affects differentiation of hippocampal neural stem cells by regulating miR-410-3p and ATN1 Yi Zhang, Ziyi Wu, Xingyue Li, Yuxiao Wan, Yinong Zhang and Ping Zhao*
Abstract Background: Currently, 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. Methods: In 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. Results: The 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. Conclusions: The 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. Keywords: Sevoflurane, Mid-trimester, Neural stem cells, Differentiation, Neurotoxicity, microRNA
Background Numerous animal studies have shown that exposure to anesthesia drugs can lead to long-term neurocognitive impairment in the developing brain. Most research has focused on the newborn period [1–3]. Because the surgical technologies are constantly advancing, the number of non-obstetric surgeries is continually increasing. Mid* Correspondence: [email protected]; [email protected] Department of Anesthesiology, Shengjing Hospital of China Medical University, Shenyang, China
trimester is considered a relatively safe period to perform surgery during pregnancy. However, the midtrimester is a critical period for fetal brains because neural stem cells (NSCs) undergo high proliferation and differentiation [4, 5]. In our previous studies [6–8], exposure to sevoflurane in the mid-trimester of pregnancy suppressed NSC proliferation and led to early apoptosis. However, whether sevoflurane affect
Data Loading...
