Xi Chen, Yu Zhang, Nan Hu, Qian Pan, Kaiyuan Wang, Yiqing Yin
{"title":"七氟醚麻醉诱导新生大鼠认知功能障碍的LncRNA GAS5调控机制","authors":"Xi Chen, Yu Zhang, Nan Hu, Qian Pan, Kaiyuan Wang, Yiqing Yin","doi":"10.1016/j.braindev.2024.10.003","DOIUrl":null,"url":null,"abstract":"<div><h3>Background and objectives</h3><div>Sevoflurane (Sev) exposure may provoke deleterious effects on cognitive function. This study explores the mechanism of long non-coding RNA growth arrest specific transcript 5 (LncRNA GAS5) in Sev-induced cognitive dysfunction in neonatal rats.</div></div><div><h3>Methods</h3><div>Cognitive dysfunction was induced by Sev anesthesia in 7-day-old Sprague-Dawley rats, followed by open field test, novel object recognition, radial arm maze, and Morris water maze to evaluate cognitive function of rats. The subcellular localization of LncRNA GAS5 was detected by nucleocytoplasmic isolation assay, and the binding of miR-137 to LncRNA GAS5 and NKCC1 was detected by RNA pull down and dual-luciferase reporter assay, respectively. Adenovirus-packaged sh-LncRNA GAS5 was injected into the hippocampus of Sev rats. qRT-PCR and Western blot were performed to detect the expressions of LncRNA GAS5, miR-137 and NKCC1 in the hippocampus of rats.</div></div><div><h3>Results</h3><div>Sev anesthesia led to cognitive dysfunction in neonatal rats. LncRNA GAS5 was highly expressed in Sev rats, and inhibition of LncRNA GAS5 alleviated Sev-induced cognitive dysfunction in rats. LncRNA GAS5 targeted miR-137, and miR-137 inhibited NKCC1 expression. Knockdown of miR-137 or overexpression of NKCC1 reversed the effect of LncRNA GAS5 inhibition on cognitive dysfunction in sev rats.</div></div><div><h3>Conclusion</h3><div>LncRNA GAS5 promotes Sev-induced cognitive dysfunction in neonatal rats via the miR-137/NKCC1 axis.</div></div>","PeriodicalId":56137,"journal":{"name":"Brain & Development","volume":"47 1","pages":"Article 104295"},"PeriodicalIF":1.4000,"publicationDate":"2024-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Regulatory mechanism of LncRNA GAS5 in cognitive dysfunction induced by sevoflurane anesthesia in neonatal rats\",\"authors\":\"Xi Chen, Yu Zhang, Nan Hu, Qian Pan, Kaiyuan Wang, Yiqing Yin\",\"doi\":\"10.1016/j.braindev.2024.10.003\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Background and objectives</h3><div>Sevoflurane (Sev) exposure may provoke deleterious effects on cognitive function. This study explores the mechanism of long non-coding RNA growth arrest specific transcript 5 (LncRNA GAS5) in Sev-induced cognitive dysfunction in neonatal rats.</div></div><div><h3>Methods</h3><div>Cognitive dysfunction was induced by Sev anesthesia in 7-day-old Sprague-Dawley rats, followed by open field test, novel object recognition, radial arm maze, and Morris water maze to evaluate cognitive function of rats. The subcellular localization of LncRNA GAS5 was detected by nucleocytoplasmic isolation assay, and the binding of miR-137 to LncRNA GAS5 and NKCC1 was detected by RNA pull down and dual-luciferase reporter assay, respectively. Adenovirus-packaged sh-LncRNA GAS5 was injected into the hippocampus of Sev rats. qRT-PCR and Western blot were performed to detect the expressions of LncRNA GAS5, miR-137 and NKCC1 in the hippocampus of rats.</div></div><div><h3>Results</h3><div>Sev anesthesia led to cognitive dysfunction in neonatal rats. LncRNA GAS5 was highly expressed in Sev rats, and inhibition of LncRNA GAS5 alleviated Sev-induced cognitive dysfunction in rats. LncRNA GAS5 targeted miR-137, and miR-137 inhibited NKCC1 expression. Knockdown of miR-137 or overexpression of NKCC1 reversed the effect of LncRNA GAS5 inhibition on cognitive dysfunction in sev rats.</div></div><div><h3>Conclusion</h3><div>LncRNA GAS5 promotes Sev-induced cognitive dysfunction in neonatal rats via the miR-137/NKCC1 axis.</div></div>\",\"PeriodicalId\":56137,\"journal\":{\"name\":\"Brain & Development\",\"volume\":\"47 1\",\"pages\":\"Article 104295\"},\"PeriodicalIF\":1.4000,\"publicationDate\":\"2024-11-16\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Brain & Development\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0387760424001360\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q4\",\"JCRName\":\"CLINICAL NEUROLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Brain & Development","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0387760424001360","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}
Regulatory mechanism of LncRNA GAS5 in cognitive dysfunction induced by sevoflurane anesthesia in neonatal rats
Background and objectives
Sevoflurane (Sev) exposure may provoke deleterious effects on cognitive function. This study explores the mechanism of long non-coding RNA growth arrest specific transcript 5 (LncRNA GAS5) in Sev-induced cognitive dysfunction in neonatal rats.
Methods
Cognitive dysfunction was induced by Sev anesthesia in 7-day-old Sprague-Dawley rats, followed by open field test, novel object recognition, radial arm maze, and Morris water maze to evaluate cognitive function of rats. The subcellular localization of LncRNA GAS5 was detected by nucleocytoplasmic isolation assay, and the binding of miR-137 to LncRNA GAS5 and NKCC1 was detected by RNA pull down and dual-luciferase reporter assay, respectively. Adenovirus-packaged sh-LncRNA GAS5 was injected into the hippocampus of Sev rats. qRT-PCR and Western blot were performed to detect the expressions of LncRNA GAS5, miR-137 and NKCC1 in the hippocampus of rats.
Results
Sev anesthesia led to cognitive dysfunction in neonatal rats. LncRNA GAS5 was highly expressed in Sev rats, and inhibition of LncRNA GAS5 alleviated Sev-induced cognitive dysfunction in rats. LncRNA GAS5 targeted miR-137, and miR-137 inhibited NKCC1 expression. Knockdown of miR-137 or overexpression of NKCC1 reversed the effect of LncRNA GAS5 inhibition on cognitive dysfunction in sev rats.
Conclusion
LncRNA GAS5 promotes Sev-induced cognitive dysfunction in neonatal rats via the miR-137/NKCC1 axis.
期刊介绍:
Brain and Development (ISSN 0387-7604) is the Official Journal of the Japanese Society of Child Neurology, and is aimed to promote clinical child neurology and developmental neuroscience.
The journal is devoted to publishing Review Articles, Full Length Original Papers, Case Reports and Letters to the Editor in the field of Child Neurology and related sciences. Proceedings of meetings, and professional announcements will be published at the Editor''s discretion. Letters concerning articles published in Brain and Development and other relevant issues are also welcome.