High-concentration sevoflurane exposure in mid-gestation induces apoptosis of neural stem cells in rat offspring

Wang, Yuan; Yin, Shaowei; Zhang, Nan; Zhao, Ping

doi:10.4103/1673-5374.237121

Cited by 30 publications

(17 citation statements)

References 50 publications

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“…Sox2 also regulates the expression of multiple genes that are critical for neuronal differentiation and maturation [ 16 ]. Although studies have shown that various insults impair learning and memory and reduce Sox2 expression [ 17 , 18 , 19 ], it is not known whether there is a causal relationship between the impaired learning and memory and decreased Sox2 expression.…”

Section: Introductionmentioning

confidence: 99%

Role of Sox2 in Learning, Memory, and Postoperative Cognitive Dysfunction in Mice

Gui

Luo

Shan

et al. 2021

Cells

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Postoperative cognitive dysfunction (POCD) is a significant clinical issue. Its neuropathogenesis has not been clearly identified and effective interventions for clinical use to reduce POCD have not been established. This study was designed to determine whether environmental enrichment (EE) or cognitive enrichment (CE) reduces POCD and whether sex-determining region Y-box-2 regulated by sirtuin 1, plays a role in the effect. Eighteen-month-old male mice were subjected to right-common-carotid-artery exposure under sevoflurane anesthesia. Some of them stayed in cages with EE or CE after the surgery. Learning and memory of mice were tested by a Barnes maze and fear conditioning, starting 2 weeks after the surgery. Sex-determining region Y-box-2 (Sox2) in the brain was silenced by small hairpin RNA (shRNA). Immunofluorescent staining was used to quantify Sox2-positive cells. Surgery reduced Sox2-positive cells in the hippocampus (64 ± 9 cells vs. 91 ± 9 cells in control group, n = 6, p < 0.001) and impaired learning and memory (time to identify target box one day after training sessions in the Barnes maze test: 132 ± 53 s vs. 79 ± 53 s in control group, n = 10, p = 0.040). EE or CE applied after surgery attenuated this reduction of Sox2 cells and POCD. Surgery reduced sirtuin 1 activity and CE attenuated this reduction. Resveratrol, a sirtuin 1 activator, attenuated POCD and surgery-induced decrease of Sox2-positive cells. Silencing shRNA reduced the Sox2-positive cells in the hippocampus and impaired learning and memory in mice without surgery. These results suggest a role of Sox2 in learning, memory, and POCD. EE and CE attenuated POCD via maintaining Sox2-positive cells in the hippocampus.

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Section: Introductionmentioning

confidence: 99%

Role of Sox2 in Learning, Memory, and Postoperative Cognitive Dysfunction in Mice

Gui

Luo

Shan

et al. 2021

Cells

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“…We were interested in whether sevoflurane, which is more commonly used clinically and is less toxic, also has concentration-dependent neurotoxicity. Our data demonstrated that sevoflurane exposure during the mid-trimester caused NSC apoptosis and impairs postnatal learning and memory function in a dose-dependent manner ( Wang et al, 2018a ). However, the mid-trimester is a critical time for NSC proliferation.…”

Section: Introductionmentioning

confidence: 75%

Effects of Pregnancy Anesthesia on Fetal Nervous System

Jiang

Zhao

2021

Front. Pharmacol.

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The effects of general anesthesia on the developing brain remain a great concern in the medical field and even in the public, and most researches in this area focus on infancy and childhood. In recent years, with the continuous development of medical technology, the number of operations during pregnancy is increasing, however, studies on general anesthesia during pregnancy are relatively lacking. The mid-trimester of pregnancy is a critical period, and is regarded as a safe period for surgery, but it is a fragile period for the development of the central nervous system and is particularly sensitive to the impact of the environment. Our research group found that general anesthesia may have adverse effects on fetal neurodevelopment during the mid-trimester. Therefore, in this review, we summarize the characteristics of anesthesia during pregnancy, and the related research of the anesthesia’s impacts on the development of central nervous system were introduced.

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“…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][7][8], exposure to sevoflurane in the mid-trimester of pregnancy suppressed NSC proliferation and led to early apoptosis. However, whether sevoflurane affects NSC differentiation remains unclear.…”

Section: Introductionmentioning

confidence: 96%

Maternal sevoflurane exposure affects differentiation of hippocampal neural stem cells by regulating miR-410-3p and ATN1

Zhang

et al. 2020

Stem Cell Res Ther

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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.

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High-concentration sevoflurane exposure in mid-gestation induces apoptosis of neural stem cells in rat offspring

Cited by 30 publications

References 50 publications

Role of Sox2 in Learning, Memory, and Postoperative Cognitive Dysfunction in Mice

Role of Sox2 in Learning, Memory, and Postoperative Cognitive Dysfunction in Mice

Effects of Pregnancy Anesthesia on Fetal Nervous System

Maternal sevoflurane exposure affects differentiation of hippocampal neural stem cells by regulating miR-410-3p and ATN1

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