Effects of Sevoflurane Exposure During Mid-Pregnancy on Learning and Memory in Offspring Rats: Beneficial Effects of Maternal Exercise

Wu, Ziyi; Li, Xingyue; Zhang, Yi; Tong, Dongyi; Wang, Lili; Zhao, Ping

doi:10.3389/fncel.2018.00122

Cited by 52 publications

(47 citation statements)

References 52 publications

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“…Over an extended period, β-tubulin III was suppressed while GFAP remained overexpressed. The reduction of β-tubulin III indicates the number of neurons was reduced, which supports the same behavioral test results obtained in our previous research showing multiple exposures to sevo urane can lead to neurocognitive impairment and learning disability in the offspring (Wu et al, 2018). Assumedly, sevo urane causes premature differentiation of NSCs which result in neuronal damage in postnatal off-spring.…”

Section: Discussionsupporting

confidence: 89%

“…Our previous study showed that a single maternal 3% sevo urane exposure does not cause long-term neurocognitive impairment in fetal rats, while repeated exposure of 3% sevo urane can cause learning and memory impairment in the offspring (Wu et al, 2018). The β-tubulin III and GFAP levels in rat brains were examined on postnatal day 28 ( Figure 4) as well as in the cultured NSCs ( Figure 5).…”

Section: Repeated Exposure To Sevo Urane Led To Early Differentiationmentioning

confidence: 97%

Section: Western Blotmentioning

confidence: 99%

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

Zhang

et al. 2020

Preprint

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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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Section: Discussionsupporting

confidence: 89%

Section: Repeated Exposure To Sevo Urane Led To Early Differentiationmentioning

confidence: 97%

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

Zhang

et al. 2020

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“…The brain tissues and collected cells were stored at -80°C before use and homogenized to determine protein expression using the western blotting protocol described in our previous study (Wu et al, 2018). The protein concentration was measured using the BCA Protein Assay Kit (P0010; Beyotime, China).…”

Section: Western Blotmentioning

confidence: 99%

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

ZHANG

et al. 2020

Preprint

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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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“…Aberrant neural differentiation has been shown to contribute to cognitive impairment and neurogenesis inhibition in young and offspring rodents [34]. Sevoflurane regulates neurogenesis in offspring rats by down-regulated the expression of brain-derived neurotrophic factor (BDNF) that is the critical neural development and disease related gene [19,[35][36][37] and induces neurotoxicity and cognitive impairment in young mice [38,39]. But, the underlying mechanism by which sevoflurane regulates the expression of BDNF remains largely unknown, which impedes further research into anesthesia neurotoxicity in the developing brain.…”

Section: Introductionmentioning

confidence: 99%

Sevoflurane regulating LncRNA Rik-203 contributes to neural differentiation via microRNA-466l-3p /BDNF pathway

Zhang

Liu

Xue

et al. 2019

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Background: The anesthetics inhibit neural differentiation, induced neuron loss and cognitive impairment in young animals. However, the underlying mechanisms of anesthesia on neural differentiation and are unknown. Methods: Embryonic stem cells (ESCs) and mice received sevoflurane anesthesia. RNA sequencing; gene expression of mRNAs, LncRNAs and miRNAs; over-expression and RNA interference of genes; flow cytometry; real-time quantity PCR and Western blot were used in the studies. RNA pull-down assay and PCR were employed to detect any miRNA that attached to Rik-203. The binding of miRNA with mRNA of BDNF was presented by the luciferase assay. Results: Here we found that LncRNA Rik-203 was higher expressed in mice brain than other tissues and increased during neural differentiation. Sevoflurane decreased the level of Rik-203 in mice brain. Knockdown of Rik-203 repressed the neural differentiation derived from mouse embryonic stem cell with the downregulation of the neural progenitor cells markers Sox1 and Nestin. RNA pull-down showed that miR-466l-3p was highly bound to Rik-203 and mediated the function of Rik-203. Inhibition of miR-466l-3p restored the neural differentiation repressed by Rik-203 knockdown. BDNF was directly targeted by miR-466l-3p and also downregulated by sevoflurane. Overexpression of BDNF restored the neural differentiation repressed by miR-466l-3p and Rik-203 knockdown. Conclusion: Our study suggested that sevoflurane related LncRNARik-203 facilitates neural differentiation by inhibiting miR-466l-3p’s ability to reduce BDNF levels. Keywords: Anesthesia; sevoflurane; Rik-203; miR-466l-3p; BDNF; neural differentiation.

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Effects of Sevoflurane Exposure During Mid-Pregnancy on Learning and Memory in Offspring Rats: Beneficial Effects of Maternal Exercise

Cited by 52 publications

References 52 publications

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

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

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

Sevoflurane regulating LncRNA Rik-203 contributes to neural differentiation via microRNA-466l-3p /BDNF pathway

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