The role of α7-nAChR /PI3K/AKT/GSK-3 pathway in chronic sleep deprivation and its mechanism
10.19845/j.cnki.zfysjjbzz.2021.0105
- VernacularTitle: α7-nAChR/PI3K/AKT/GSK-3β通路在慢性睡眠剥夺后的保护作用及其机制研究
- Author:
Yahui WAN
1
;
Mengdi LV
1
;
Zheng LI
1
Author Information
1. Department of Neurology，Tianjin Medical University General Hospital Airport Hospital，Tianjin 300000，China
- Publication Type:Journal Article
- Keywords:
Chronic sleep deprivation ； α-7 nAChR ； Glial cells ； Inflammatory response
- From:
Journal of Apoplexy and Nervous Diseases
2021;38(5):392-398
- CountryChina
- Language:Chinese
-
Abstract:
Objective Investigated the influences of chronic sleep deprivation on the expression α7-nAChR and the activity of its downstream PI3K/AKT/GSK-3β pathway in neuroglia in mice.Methods Adult C57BL/6J mice aged 7-8 weeks were randomly divided into three groups，control（CC）group，chronic sleep deprivation（SD） group，chronic sleep deprivation + intraperitoneal injection α7-nAChR agonists PHA-543613（SD + PHA - 543613） group.The protein expression of α7 -nAChR,p-AKT,p-GSK-3β,Nrf-2,HO-1 in mice hippocampus were examined by Western Blot，the gene expression of α7 -nAChR and the gene expression of TNF-α,IL-1β,IFN-γ,MCP-1,Arg-1,CD206,TGF-β,YM-1 were examined by Rt-PCR；the expression of α7-nAChR on astrocytes and microglias in mice hippocampus were assesed by double-labeled immunofluorescence.Spatial learning and memory was assessed by morris water maze （MWM） test.Results After chronic sleep deprivation for 7 days，the expression of α7-nAChR protein，mRNA in SD group decreased significantly when compared with CC group（P=0.001,P=0.038）;the expression of protein p-AKT decreased in SD group compared with CC group（P=0.019）,while the expression of protein p-GSK-3β increased in SD group compared with CC group（P=0.011）.Afterα7-nAChR agonists PHA-543613 treatment,the expression of α-7 nAChR on astrocytes increased significantly when compared with SD group（P=0.027，the expression of p-AKT and p-GSK-3βincreased when compared with SD group（P=0.047,P=0.017.At the same time，the expression of Nrf-2，HO-1 and anti-inflammatory factors（CD206，TGF-β）increased significantly compared with SD group（P=0.020,P=0.016，P<0.01,P<0.01），while the expression of inflammatory factors（TNF-α，MCP-1） decreased compared with SD group（P<0.01）.After α7-nAChR agonists PHA-543613 treatment，the escape latency at the end of experiment was decreased，the frequency of crossing platforms and the time in the target quadrant was prolonged compared to the SD group（P=0.000,P=0.000,P=0.001）.Conclusion Stimulation of α7-nAChR reduces inflammation and oxidative stress via activation of PI3K/AKT /GSK-3β after chronic sleep deprivation.
- Full text:202407292228246933The role of α7nAChR PI3K_AKT_GSK-3 pathway in chronic sleep deprivation and its mechanism.pdf
