Neurodevelopmental abnormalities underlying behavioral deficits in a model of pediatric obstructive sleep apnea.

RATIONALE: Pediatric Obstructive Sleep Apnea (POSA) is a relatively common childhood sleep disorder whose neurodevelopmental phenotype includes deficits in learning and memory, olfaction, and fine motor abilities.

OBJECTIVES

To date, there has not been a validated preclinical model of POSA, hampering efforts in understanding how nocturnal episodes of intermittent hypoxia disrupt neurodevelopmental trajectories. The objective of this study was to create a faithful sculpting of the human condition in a preclinical murine model.

METHODS

We used clinical data from children with POSA to develop and validate a mouse model of POSA that faithfully recapitulates several behavioral deficits seen in the human condition. We then studied synapses, and cellular constituents of neurogenic niches to interrogate the behavioral deficits.

MEASUREMENTS AND MAIN

RESULTS

POSA mice showed deficits in postnatal neurogenesis in both the subventricular zone and hippocampus. Specifically, we discovered fewer neural stem cells, neuroblasts, and newborn neurons in POSA mice.

CONCLUSIONS

This reduction in developmental neurogenesis was coupled with impaired functional integration of post exposure born neurons in the hippocampus and olfactory bulb. Taken together, our findings from this preclinical model based on human data indicate that POSA disrupts developmental neurogenesis and neuronal maturation, resulting in deficits in learning, memory, olfactory, and fine motor abilities.