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Cognitive function in prepubertal children with obstructive sleep apnea: a modifying role for NADPH oxidase p22 subunit gene polymorphisms?

ABSTRACT: Pediatric obstructive sleep apnea (OSA) may lead to neurocognitive dysfunction, but not in everyone affected. The frequencies of NADPH oxidase (NOX) polymorphisms in the p22phox subunit were similar between children with OSA and controls, except for rs6520785 and rs4673, the latter being significantly more frequent among the OSA children without deficits than with deficits (p<0.02). Similarly, 8-hydroxydeoxyguanine urine levels and NOX activity were lower among children without cognitive deficits and particularly among those with the rs4673 polymorphism. Thus, polymorphisms within the NOX gene or its functional subunits may account for important components of the variance in cognitive function deficits associated with OSA in children.

SUBMITTER: Gozal D

PROVIDER: S-EPMC3250922 | biostudies-literature | 2012 Jan

REPOSITORIES: biostudies-literature

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Cognitive function in prepubertal children with obstructive sleep apnea: a modifying role for NADPH oxidase p22 subunit gene polymorphisms?

Gozal David D Khalyfa Abdelnaby A Capdevila Oscar Sans OS Kheirandish-Gozal Leila L Khalyfa Ahamed A AA Kim Jinkwan J

Antioxidants & redox signaling 20111012 2

Pediatric obstructive sleep apnea (OSA) may lead to neurocognitive dysfunction, but not in everyone affected. The frequencies of NADPH oxidase (NOX) polymorphisms in the p22phox subunit were similar between children with OSA and controls, except for rs6520785 and rs4673, the latter being significantly more frequent among the OSA children without deficits than with deficits (p<0.02). Similarly, 8-hydroxydeoxyguanine urine levels and NOX activity were lower among children without cognitive deficit ...[more]

PMID: 21902598

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Project description:Persons with obstructive sleep apnea may have significant residual hypersomnolence, despite therapy. Long-term hypoxia/reoxygenation events in adult mice, simulating oxygenation patterns of moderate-severe sleep apnea, result in lasting hypersomnolence, oxidative injury, and proinflammatory responses in wake-active brain regions. We hypothesized that long-term intermittent hypoxia activates brain NADPH oxidase and that this enzyme serves as a critical source of superoxide in the oxidation injury and in hypersomnolence.We sought to determine whether long-term hypoxia/reoxygenation events in mice result in NADPH oxidase activation and whether NADPH oxidase is essential for the proinflammatory response and hypersomnolence.NADPH oxidase gene and protein responses were measured in wake-active brain regions in wild-type mice exposed to long-term hypoxia/reoxygenation. Sleep and oxidative and proinflammatory responses were measured in adult mice either devoid of NADPH oxidase activity (gp91phox-null mice) or in which NADPH oxidase activity was systemically inhibited with apocynin osmotic pumps throughout hypoxia/reoxygenation.Long-term intermittent hypoxia increased NADPH oxidase gene and protein responses in wake-active brain regions. Both transgenic absence and pharmacologic inhibition of NADPH oxidase activity throughout long-term hypoxia/reoxygenation conferred resistance to not only long-term hypoxia/reoxygenation hypersomnolence but also to carbonylation, lipid peroxidation injury, and the proinflammatory response, including inducible nitric oxide synthase activity in wake-active brain regions.Collectively, these findings strongly support a critical role for NADPH oxidase in the lasting hypersomnolence and oxidative and proinflammatory responses after hypoxia/reoxygenation patterns simulating severe obstructive sleep apnea oxygenation, highlighting the potential of inhibiting NADPH oxidase to prevent oxidation-mediated morbidities in obstructive sleep apnea.

Dataset Information

Cognitive function in prepubertal children with obstructive sleep apnea: a modifying role for NADPH oxidase p22 subunit gene polymorphisms?

Publications

Cognitive function in prepubertal children with obstructive sleep apnea: a modifying role for NADPH oxidase p22 subunit gene polymorphisms?

Similar Datasets

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