Altered Wnt Signaling Pathway in Cognitive Impairment Caused by Chronic Intermittent Hypoxia： Focus on Glycogen Synthase Kinase-3β and β-catenin  

作　　者：Yue-Ying Pan Yan Deng Sheng Xie Zhi-Hua Wang YuWang Jie Ren Hui-Guo Liu 

机构地区：[1]Department of Respiratory and Critical Care Medicine, Tongji Hospital, Tongli Medical College, Huazhong University of Science and Technology, Key Laboratory of Respiratory Disease of the Ministry of Health, Wuhan, Hubei 430030, China

出　　处：《Chinese Medical Journal》2016年第7期838-845,共8页中华医学杂志（英文版）

基　　金：This work was supported by a grant from the National Natural Science Foundation of China （No. 81370185）.

摘　　要：Background： Cognitive impairment is a severe complication caused by obstructive sleep apnea （OSA）. The mechanisms of causation are still unclear. The Wntβ-catenin signaling pathway is involved in cognition, and abnormalities in it are implicated in neurological disorders. Here, we explored the Wntβ-catenin signaling pathway abnormalities caused by chronic intermittent hypoxia （CIH）, the most characteristic pathophysiological component of OSA. Methods： We divided 32 4-week-old male C57/BL mice into four groups of eight each： a CIH ＋ normal saline （NS） group, CIH ＋ LiCI group, sham CIH ＋ NS group, and a sham CIH ＋ LiCI group. The spatial learning performance of each group was assessed by using the Morris water maze （MWM）. Protein expressions of glycogen synthase kinase-β （GSK-β） and β-catenin in the hippocampus were examined using the Western blotting test. EdU labeling and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling staining methods were used, respectively, to determine the proliferation and apoptosis of neurons in the hippocampal dentate gyrus region. Results： Mice exposed to CIH showed impaired spatial learning performance in the MWM, including increased mean escape latencies to reach the target platform, decreased mean times passing through the target platform and mean duration in the target quadrant. The GSK-313 activity increased, and expression of β-catenin decreased significantly in the hippocampus of the CIH-exposed mice. Besides, CIH significantly increased hippocampal neuronal apoptosis, with an elevated apoptosis index. Meanwhile, LiCI decreased the activity of GSK-β and increased the expression of β-catenin and partially reversed the spatial memory deficits in MWM and the apoptosis caused by CIH. Conclusions： Wntβ-catenin signaling pathway abnormalities possibly play an important role in the development of cognitive deficits among mice exposed to CIH and that LiCI might attenuate CIH-induced cognitive impairment via Wntβ-cBackground： Cognitive impairment is a severe complication caused by obstructive sleep apnea （OSA）. The mechanisms of causation are still unclear. The Wntβ-catenin signaling pathway is involved in cognition, and abnormalities in it are implicated in neurological disorders. Here, we explored the Wntβ-catenin signaling pathway abnormalities caused by chronic intermittent hypoxia （CIH）, the most characteristic pathophysiological component of OSA. Methods： We divided 32 4-week-old male C57/BL mice into four groups of eight each： a CIH ＋ normal saline （NS） group, CIH ＋ LiCI group, sham CIH ＋ NS group, and a sham CIH ＋ LiCI group. The spatial learning performance of each group was assessed by using the Morris water maze （MWM）. Protein expressions of glycogen synthase kinase-β （GSK-β） and β-catenin in the hippocampus were examined using the Western blotting test. EdU labeling and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling staining methods were used, respectively, to determine the proliferation and apoptosis of neurons in the hippocampal dentate gyrus region. Results： Mice exposed to CIH showed impaired spatial learning performance in the MWM, including increased mean escape latencies to reach the target platform, decreased mean times passing through the target platform and mean duration in the target quadrant. The GSK-313 activity increased, and expression of β-catenin decreased significantly in the hippocampus of the CIH-exposed mice. Besides, CIH significantly increased hippocampal neuronal apoptosis, with an elevated apoptosis index. Meanwhile, LiCI decreased the activity of GSK-β and increased the expression of β-catenin and partially reversed the spatial memory deficits in MWM and the apoptosis caused by CIH. Conclusions： Wntβ-catenin signaling pathway abnormalities possibly play an important role in the development of cognitive deficits among mice exposed to CIH and that LiCI might attenuate CIH-induced cognitive impairment via Wntβ-c

关 键 词：Β-CATENIN Chronic Intermittent Hypoxia Cognition Glycogen Synthase kinase-3β Hippocampus Obstructive SleepApnea 

分 类 号：Q954.4[生物学—动物学] Q2