Neonatal obstructive sleep apneas in a mouse model of Down syndrome.

Abstract

Down syndrome (DS) is a genetic disease caused by a third copy of chromosome 21, leading to various physical features, developmental and cognitive delays, and intellectual disability. Obstructive sleep apnea (OSA) is highly prevalent in children with DS, with severity reported to be inversely related to age and culminating in neonates. OSA causes intermittent hypoxia and hypercapnia, which may have detrimental effects on health and development. Consequently, there are concerns about the impact of OSA on neurodevelopmental disorders associated with DS, particularly in neonates. Dp(16)1Yey mice, a genetically engineered model of DS, exhibit cognitive impairments and characteristics typically associated with OSA, including craniofacial hypoplasia and reduced upper airway volume in adulthood. To investigate the contribution of respiratory-related disorders to DS pathophysiology, we examined the cardio-respiratory phenotype of Dp(16)1Yey mice at birth, with special attention to OSA, using a pneumotachograph and a facemask combined with a laser abdominal profilometer to distinguish obstructive, central, and mixed apneas. Dp(16)1Yey mouse pups exhibited lower weight and heart rates compared to their wild-type counterparts. Baseline breathing variables and responses to hypercapnia were similar between the two groups. Obstructive apneas were observed in both Dp(16)1Yey and wild-type mice, but the total time spent in obstructive apneas was longer in Dp(16)1Yey mice, due to their longer mean duration. These findings highlight the relevance of the Dp(16)1Yey model for studying OSA in DS during the neonatal period and for investigating the contribution of early respiratory disorders to DS pathology.NEW & NOTEWORTHY Severe obstructive sleep apnea is prevalent in neonates with Down syndrome, but neonatal breathing disorders remain unexplored in mouse models. Using the Dp(16)1Yey model, we observed prolonged obstructive apneas and lower heart rates at birth in mutant pups compared to wild-type littermates. This preclinical model provides a novel platform to study neonatal obstructive sleep apnea in Down syndrome and its contribution to neurodevelopmental disorders associated with Down syndrome.