Sevoflurane Inhibits Neurogenesis and the Wnt-Catenin Signaling Pathway in Mouse Neural Progenitor Cells

Zhang, Y.; Dong, Yuanlin; Zheng, Hongwu; Shie, V.; Wang, Hairong; Busscher, J. J.; Yue, Yili; Xu, Zhejun; Xie, Zhihui

doi:10.2174/15665240113139990073

Cited by 48 publications

(42 citation statements)

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“…Moreover, in an in vitro study, Zhang et al found that treatment with 4.1% sevoflurane for six hours in mouse neural progenitor cells increased the levels of GSK3β (Figure 3 in the manuscript by Zhang et al) 74 . The studies by Zhang et al, however, did not measure the effects of sevoflurane on the levels of P-GSK3β(ser9).…”

Section: Discussionmentioning

confidence: 97%

Sevoflurane Induces Tau Phosphorylation and Glycogen Synthase Kinase 3β Activation in Young Mice

et al. 2014

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Background Children with multiple exposures to anesthesia and surgery may have an increased risk of developing cognitive impairment. Sevoflurane is a commonly used anesthetic in children. Tau phosphorylation contributes to cognitive dysfunction. We therefore assessed the effects of sevoflurane on Tau phosphorylation and underlying mechanisms in young mice. Methods Six day-old wild-type (WT) and Tau knockout (KO) mice were exposed to sevoflurane. We determined the effects of the sevoflurane anesthesia on Tau phosphorylation, levels of the kinases and phosphatase related to Tau phosphorylation, interleukin-6, and postsynaptic density protein 95 (PSD-95) in hippocampus, and cognitive function in both young WT and Tau KO mice. Results Anesthesia with 3% sevoflurane two hours daily for three days induced Tau phosphorylation (257% versus 100%, P=0.0025, n=6), enhanced activation of glycogen synthase kinase 3β (GSK3β), the kinase related to Tau phosphorylation in the hippocampus of postnatal day 8 WT mice. The sevoflurane anesthesia decreased hippocampus PSD-95 levels and induced cognitive impairment in the postnatal day 31 mice. GSK3β inhibitor lithium inhibited the sevoflurane-induced GSK3β activation, Tau phosphorylation, elevated levels of interleukin-6 and cognitive impairment in the WT young mice. Finally, the sevoflurane anesthesia did not induce an elevation of interleukin-6 levels, reduction in PSD-5 levels in hippocampus, or cognitive impairment in Tau KO young mice. Conclusions These data suggested that sevoflurane induced Tau phosphorylation, GSK3β activation, elevation of interleukin-6 and reduction of PSD-95 levels in hippocampus of young mice, and cognitive impairment in the mice. Future studies will dissect the cascade relationship of these effects.

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Section: Discussionmentioning

confidence: 97%

Sevoflurane Induces Tau Phosphorylation and Glycogen Synthase Kinase 3β Activation in Young Mice

et al. 2014

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“…However, it has been shown to induce cognitive impairment in rodents and might be associated with a higher incidence of learning and memory impairment in humans, leading to increased cost, morbidity, and mortality (Nikizad et al, 2007;Wilder et al, 2009;Zhang et al, 2013a). In recent studies, researchers have shown many adverse effects caused by sevoflurane on the developing brain especially in the embryonic period, neonatal period, and infancy (Shen et al, 2013;Zheng et al, 2013;Zhang et al, 2013b). They concluded that sevoflurane could increase neurodegeneration in the developing hippocampus of fetal rats.…”

Section: Introductionmentioning

confidence: 99%

Sevoflurane induces neurotoxicity in young mice through FAS/FASL signaling

Song

et al. 2015

Genet. Mol. Res.

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ABSTRACT. Sevoflurane, the most widely used anesthetic in clinical practice, has been shown to induce apoptosis, inhibit neurogenesis, and cause learning and memory impairment in young mice. However, the underlying mechanism is still unknown. In this study, wild-type and the FAS-or FAS ligand (FASL)-knockout mice (age 7 days) were exposed to sevoflurane or pure oxygen. Western blotting was used to examine the expression of FAS protein.Terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) and bromodeoxyuridine (BrdU) staining were employed to quantify the apoptotic cells and newborn cells in the hippocampus and Morris water maze (MWM) in order to evaluate learning and memory status. Sevoflurane significantly increased the expression of FAS protein in wild-type mice. Compared to FASand FASL-knockout mice treated with sevoflurane, sevoflurane-treated wildtype mice exhibited more TUNEL-positive hippocampal cells and less BrdU- (2015) positive hippocampal cells. The MWM showed that compared with FAS-and FASL-knockout mice treated with sevoflurane, sevoflurane treatment of wildtype mice significantly prolonged the escape latency and reduced platform crossing times. These data suggest that sevoflurane induces neurotoxicity in young mice through FAS-FASL signaling.

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“…Previous studies showed that sevoflurane could inhibit the central nervous system by activating the GABA A receptor, resulting in cell apoptosis and degeneration of NSCs24. Sevoflurane may reduce neurogenesis through the Wnt–catenin signaling pathway25. The phosphorylation level of ERK1/2 increased after 1-h exposure to 1 or 1.5 MAC of sevoflurane in the proliferation phase, but not in the differentiation phase26.…”

Section: Discussionmentioning

confidence: 94%

Sevoflurane decreases self-renewal capacity and causes c-Jun N-terminal kinase–mediated damage of rat fetal neural stem cells

Yang

et al. 2017

Sci Rep

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Increasing studies have demonstrated that sevoflurane can induce neurotoxicity in the developing brains. JNK normally promotes apoptosis. It was hypothesized that sevoflurane affected the proliferation and differentiation of FNSCs and induced cell apoptosis, which caused the learning and memory deficits via JNK pathway. Sevoflurane at a concentration of 1.2% did not induce damage on the FNSCS. However, concentrations of 2.4% and 4.8% decreased the cell viability, as shown by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, and increased apoptosis, as shown by flow cytometry. The 5-ethynyl-2′-deoxyuridine (EdU) incorporation assay demonstrated that 4.8% sevoflurane reduced the proliferation of FNSCs. Compared with the control group, the 4.8% sevoflurane group showed a decrease in the proportion of undifferentiated FNSCs at 6-h exposure; 4.8% sevoflurane could increase the p-JNK/JNK ratio. JNK inhibition by the specific inhibitor SP600125 enhanced partially the cell viability. Cumulatively, 4.8% sevoflurane induced significant damage on FNSCs; it decreased cell proliferation and proportion of undifferentiated cells as well. JNK pathway might play a key role in the decrease in survival of FNSCs induced by an inhaled anesthetic. The present findings might raise the possibility that JNK inhibition has therapeutic potential in protecting FNSCs from the adverse effects of the inhaled anesthetic.

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Sevoflurane Inhibits Neurogenesis and the Wnt-Catenin Signaling Pathway in Mouse Neural Progenitor Cells

Cited by 48 publications

References 0 publications

Sevoflurane Induces Tau Phosphorylation and Glycogen Synthase Kinase 3β Activation in Young Mice

Sevoflurane Induces Tau Phosphorylation and Glycogen Synthase Kinase 3β Activation in Young Mice

Sevoflurane induces neurotoxicity in young mice through FAS/FASL signaling

Sevoflurane decreases self-renewal capacity and causes c-Jun N-terminal kinase–mediated damage of rat fetal neural stem cells

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