title: Altered Wnt Signaling Pathway in Cognitive Impairment Caused by Chronic Intermittent Hypoxia: Focus on Glycogen Synthase Kinase-3β and β-catenin.
abstract: BACKGROUND
  Cognitive impairment is a severe complication caused by obstructive sleep apnea (OSA). The mechanisms of causation are still unclear. The Wnt/β-catenin signaling pathway is involved in cognition, and abnormalities in it are implicated in neurological disorders. Here, we explored the Wnt/β-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 + LiCl group, sham CIH + NS group, and a sham CIH + LiCl group. The spatial learning performance of each group was assessed by using the Morris water maze (MWM). Protein expressions of glycogen synthase kinase-3β (GSK-3β) 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-3β 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, LiCl decreased the activity of GSK-3β and increased the expression of β-catenin and partially reversed the spatial memory deficits in MWM and the apoptosis caused by CIH.
  
  
  CONCLUSIONS
  Wnt/β-catenin signaling pathway abnormalities possibly play an important role in the development of cognitive deficits among mice exposed to CIH and that LiCl might attenuate CIH-induced cognitive impairment via Wnt/β-catenin signaling pathway.
authors.forename: Yue-Ying
authors.initials: YY
authors.lastname: Pan
authors.forename: Yan
authors.initials: Y
authors.lastname: Deng
authors.forename: Sheng
authors.initials: S
authors.lastname: Xie
authors.forename: Zhi-Hua
authors.initials: ZH
authors.lastname: Wang
authors.forename: Yu
authors.initials: Y
authors.lastname: Wang
authors.forename: Jie
authors.initials: J
authors.lastname: Ren
authors.affiliation: Department of Respiratory and Critical Care Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Key Laboratory of Respiratory Disease of the Ministry of Health, Wuhan, Hubei 430030, China.
authors.forename: Hui-Guo
authors.initials: HG
authors.lastname: Liu
mesh_terms: D000818:Animals; D002908:Chronic Disease; D060825:Cognitive Dysfunction / Q000209:etiology / Q000503:physiopathology*; D000071679:Glycogen Synthase Kinase 3 beta / Q000502:physiology*; D000860:Hypoxia / Q000150:complications* / Q000503:physiopathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D060449:Wnt Signaling Pathway / Q000502:physiology*; D051176:beta Catenin / Q000502:physiology*
chemical_list: C495267:CTNNB1 protein, mouse; D051176:beta Catenin; D000071679:Glycogen Synthase Kinase 3 beta