Altered Wnt Signaling Pathway in Cognitive Impairment Caused by Chronic Intermittent Hypoxia

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.

Fork Head Box Class O1 (FOXO1) Activates Bim Expression to Mediate Cardiac Apoptosis in Chronic Intermittent Hypoxia-Induced Cardiac Hypertrophy

“…Sprague-Dawley rats (adult males, weighing 200–250 g) were purchased from the Laboratory Animal Center, Tongji Medical College. The chronic intermittent hypoxic (CIH) rats were placed in a normobaric chamber (Oxycycler modelA84XOV; BioSpherix, Lacona, NY), and then the O 2 level was reduced from the normal level to 8–10% within 120 s and maintained at approximately 8–10% for 120 s. Subsequently, the oxygen concentration was quickly increased to 21% within 50 s and maintained at this level for 300 s. This process was repeated 8 h/day for a total of 6 weeks, consistent with the experimental procedure of our previous study [ 16 ]. The CIH rats were given a dose of AS1842856 (5 mg/kg) or vehicle on days 28 to 42 at random.…”

Impaired learning and memory in rats induced by a high‐fat diet: Involvement with the imbalance of nesfatin‐1 abundance and copine 6 expression

“…Increasing evidence from animal studies and human research has indicated a role for the Wnt/β‐catenin pathway in the regulation of cognition in the adult brain . The main biological effect of the canonical Wnt/β‐catenin pathway is to regulate the degradation of β‐catenin through GSK‐3β, and regulating the activity and level of GSK‐3β and β‐catenin has been considered as a potential target for improving cognition .…”

Effect of Rapid Eye Movement Sleep Behavior Disorder on Obstructive Sleep Apnea Severity and Cognition of Parkinson's Disease Patients

“…[ 15 16 17 ] Emerging evidence indicates that, in the healthy population, cognitive impairment is a severe OSA complication. [ 18 ] In PD, OSA may be associated with increased nonmotor symptoms, particularly cognitive dysfunction. [ 19 ] However, considering RBD may relieve hypoxemia in PD patients with OSA, whether this amelioration protects against cognitive decline is unclear.…”