0050 Pediatric OSA and neurodevelopment

Abstract

Abstract Introduction Pediatric OSA and its associated sleep disorders occur in up to 7% of children. Whereas the sequelae of the disease are well characterized, the underpinnings of its phenotypes are poorly understood. This is mainly because of a lack of comprehensive model of the disease in the young. Here I present the neurobehavioral phenotype of pediatric OSA utilizing a preclinical murine model. Methods This proposal represents a departure from prior models and is embedded in the sculpting of the IH model. 1) Human polysomnographic data: We studied human data in children with OSA 2) Murine oximetry data: we create murine oximetry curves 3) Cross Species Curve Fitting: We cross fit those across species 4) Optimization of hypoxic gas throughputs: We then optimized this for the hypoxia chamber we are using Results We examined 4 behavioral tasks over a number of time periods to establish the temporality needed for hippocampal task ablation, as the hippocampus is the center of learning and memory in mammals. 2 tasks were hippocampal dependent: a) Novel object recognition b) Object place recognition. 2 tasks were hippocampal independent: 1) Hot plate: 2) OFA. We utilized 3 time periods initially: exposure from p14 to p23 (9 days acute), to p35 (21 days intermediate), and p70 (56 days, chronic). There was no deterioration in hippocampal tasks from p14 to p35, however at p70 we noted task ablation. We therefore systematically worked backwards, until we discovered the 'tipping point' where hippocampal task ablation is observed is p49 (35 days of exposure). Prior to this, we note no task ablation, however after this time point, hippocampal task ablation is preserved. Conclusion We have demonstrated a tractable, temporal model for pediatric OSA over a systematic set of time points to show when hippocampal deficits from the OSA stimulus manifest phenotypically. We have further isolated these deficits to the hippocampus of developing mice, which is the mammalian center of learning, memory, and retrieval. Support (if any) Arvind has previously received support from AASM and BCM OOR. He is currently supported by 1K08HL161263-01 from NHLBI.