Rui Su1, Ping Sun2, Dianhong Zhang3, Wei Xiao4, Chun Feng1, Liang Zhong1. 1. Department of Anesthesiology, Wuhan Children's Hospital (Wuhan Meternal and Child Healthcare Hospital), Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430016, Hubei, China. 2. Department of Anesthesiology, Wuhan Third Hospital-Tongren Hospital of Wuhan University, Wuhan, 430000, Hubei, China. 3. Department of Anesthesiology, The Hospital of Shunyi District Beijing, Beijing, 101300, China. 4. Department of Anesthesiology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430000, Hubei, China. WeiXiaosdr@163.com.
Abstract
BACKGROUND: Postoperative cognitive dysfunction (POCD) is a neurodegenerative disorder with impairment of cognition. Sevoflurane anesthesia has been found to lead to CD and microRNAs (miRNAs) were reported to affect cognitive function. This study investigates the neuroprotective effect against sevoflurane anesthesia-induced CD. METHODS: HE staining was used to detect the pathological change of hippocampal neuron. Morris water maze test was used to analyze latency time, platform crossing and swimming speed. Quantitative real-time PCR (qRT-PCR) and western blotting were performed to examine the mRNA and protein expression of miR-410-3p, IL-6, TNF-α, IL-1β and C-X-C motif chemokine receptor 5 (CXCR5). Dual-luciferase reporter assay was used to detect the relationship between miR-410-3p and CXCR5. RESULTS: MiR-410-3p was downregulated in sevoflurane anesthesia-induced rats and cells and act as a suppressor in sevoflurane anesthesia-induced hippocampal neuron apoptosis and inflammation. Furthermore, miR-410-3p was identified to bind with CXCR5. Further analysis showed that CXCR5 expression was increased by sevoflurane treatment, whereas was repressed by miR-410-3p overexpression. Moreover, miR-410-3p could inhibit sevoflurane anesthesia-induced hippocampal neuron apoptosis by phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) pathway. CONCLUSION: These data indicated that miR-410-3p exhibited its neuroprotective effect on sevoflurane anesthesia-induced CD by targeting CXCR5 via PI3K/Akt signaling pathway. Our study may potentially provide a new light on the pathogenesis and therapeutic method for sevoflurane anesthesia-induced CD.
BACKGROUND:Postoperative cognitive dysfunction (POCD) is a neurodegenerative disorder with impairment of cognition. Sevoflurane anesthesia has been found to lead to CD and microRNAs (miRNAs) were reported to affect cognitive function. This study investigates the neuroprotective effect against sevoflurane anesthesia-induced CD. METHODS:HE staining was used to detect the pathological change of hippocampal neuron. Morris water maze test was used to analyze latency time, platform crossing and swimming speed. Quantitative real-time PCR (qRT-PCR) and western blotting were performed to examine the mRNA and protein expression of miR-410-3p, IL-6, TNF-α, IL-1β and C-X-C motif chemokine receptor 5 (CXCR5). Dual-luciferase reporter assay was used to detect the relationship between miR-410-3p and CXCR5. RESULTS:MiR-410-3p was downregulated in sevoflurane anesthesia-induced rats and cells and act as a suppressor in sevoflurane anesthesia-induced hippocampal neuron apoptosis and inflammation. Furthermore, miR-410-3p was identified to bind with CXCR5. Further analysis showed that CXCR5 expression was increased by sevoflurane treatment, whereas was repressed by miR-410-3p overexpression. Moreover, miR-410-3p could inhibit sevoflurane anesthesia-induced hippocampal neuron apoptosis by phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) pathway. CONCLUSION: These data indicated that miR-410-3p exhibited its neuroprotective effect on sevoflurane anesthesia-induced CD by targeting CXCR5 via PI3K/Akt signaling pathway. Our study may potentially provide a new light on the pathogenesis and therapeutic method for sevoflurane anesthesia-induced CD.
Authors: Aditya Ganju; Sheema Khan; Bilal B Hafeez; Stephen W Behrman; Murali M Yallapu; Subhash C Chauhan; Meena Jaggi Journal: Drug Discov Today Date: 2016-11-01 Impact factor: 7.851
Authors: J T Moller; P Cluitmans; L S Rasmussen; P Houx; H Rasmussen; J Canet; P Rabbitt; J Jolles; K Larsen; C D Hanning; O Langeron; T Johnson; P M Lauven; P A Kristensen; A Biedler; H van Beem; O Fraidakis; J H Silverstein; J E Beneken; J S Gravenstein Journal: Lancet Date: 1998-03-21 Impact factor: 79.321