Metoprolol prevents neuronal dendrite remodeling in a canine model of chronic obstructive sleep apnea

Abstract

Obstructive sleep apnea (OSA) is closely associated with central nervous system diseases and could lead to autonomic nerve dysfunction, which is often seen in neurodegenerative diseases. Previous studies have shown that metoprolol prevents several chronic OSA-induced cardiovascular diseases through inhibiting autonomic nerve hyperactivity. It remains unclear whether chronic OSA can lead to dendritic remodeling in the brain, and whether metoprolol affects the dendritic remodeling. In this study we investigated the effect of metoprolol on dendrite morphology in a canine model of chronic OSA, which was established in beagles through clamping and reopening the endotracheal tube for 4 h every other day for 12 weeks. OSA beagles were administered metoprolol (5 mg· kg −1 · d −1 ). The dendritic number, length, crossings and spine density of neurons in hippocampi and prefrontal cortices were assessed by Golgi staining. And the protein levels of hypoxia-inducible factor-1α (HIF-1α) and brain-derived neurotrophic factor (BDNF) were measured by Western blotting. We showed that chronic OSA successfully induced significant brain hypoxia evidenced by increased HIF-1α levels in CA1 region and dentate gyrus of hippocampi, as well as in prefrontal cortex. Furthermore, OSA led to markedly decreased dendrite number, length and intersections, spine loss as well as reduced BDNF levels. Administration of metoprolol effectively prevented the dendritic remodeling and spine loss induced by chronic OSA. In addition, administration of metoprolol reversed the decreased BDNF, which might be associated with the metoprolol-induced neuronal protection. In conclusion, metoprolol protects against neuronal dendritic remodeling in hippocampi and prefrontal cortices induced by chronic OSA in canine.

BDNF and proBDNF Serum Protein Levels in Obstructive Sleep Apnea Patients and Their Involvement in Insomnia and Depression Symptoms

“…The majority of evidence indicates that intermittent hypoxia, one of the most damaging effects of OSA, causes decreases in BDNF levels in animal models [ 48 , 49 , 50 , 51 , 52 , 53 , 54 ]. Fang et al studied the influence of CIH (chronic intermittent hypoxia) on neurodegeneration of the optic nerve in mice model, showing decreased BDNF levels.…”

Functional connectivity changes in the insular subregions of patients with obstructive sleep apnea after 6 months of continuous positive airway pressure treatment: a resting-state functional magnetic resonance imaging study.

“…Anatomical studies have shown that the insula consists of ventral anterior, dorsal anterior, and posterior lobe subregions previous study reported that neuronal activity between the dorsomedial prefrontal cortex and anterior insula is critical in emotion management techniques (Dörfel et al 2014). In an animal experiment, chronic hypoxia caused a signi cant reduction in the number, length, and crossover point of neuronal dendrites in the prefrontal cortex, ultimately causing neuronal remodeling (Yang et al 2020). According to rs-fMRI studies, structural and functional abnormalities in the mPFC of OSA patients are related to cognitive impairment (Zhang et al 2013).…”

Effect of non-invasive ventilator in combination with tiotropium bromide on pulmonary function and sleep quality of patients with chronic obstructive pulmonary disease complicated with obstructive sleep apnea-hypopnea syndrome

“…Clinical studies show that OSAHS is complicated with COPD in about 10 % of patients, while 50 % of patients with moderate and severe COPD have OSAHS complication [12][13][14][15]. In recent years, with advancements in social economy, the incidence of COPD-OSAHS has significantly increased due to environmental pollution, smoking, obesity, and unbalanced diet.…”