Adverse cognitive effects of high-fat diet in a murine model of sleep apnea are mediated by NADPH oxidase activity.
Intermittent hypoxia (IH) during sleep, such as occurs in sleep apnea (SA), induces increased NADPH oxidase activation and deficits in hippocampal learning and memory. Similar to IH, high fat-refined carbohydrate diet (HFD), a frequent occurrence in patients with SA, can also induce similar oxidative stress and cognitive deficits under normoxic conditions, suggesting that excessive NADPH oxidase activity may underlie CNS dysfunction in both conditions. The effect of HFD and IH during the light period on two forms of spatial learning in the water maze as well as on markers of oxidative stress was assessed in male mice lacking NADPH oxidase activity (gp91phox⁻/Y) and wild-type littermates fed on HFD. On a standard place training task, gp91phox⁻/Y displayed normal learning, and was protected from the spatial learning deficits observed in wild-type littermates exposed to IH. Moreover, anxiety levels were increased in wild-type mice exposed to HFD and IH as compared to controls, while no changes emerged in gp91phox⁻/Y mice. Additionally, wild-type mice, but not gp91phox⁻/Y mice, had significantly elevated levels of malondialdehyde (MDA) and 8-hydroxydeoxyguanosine (8-OHdG) in hippocampal lysates following IH-HFD exposures. The cognitive deficits of obesity and westernized diets and those of sleep disorders that are characterized by IH during sleep are both mediated, at least in part, by excessive NADPH oxidase activity.
Department of Pediatrics, Pritzker School of Medicine, The University of Chicago, Chicago, IL, United States.
D
D
Nair
V
V
Ramesh
D
D
Gozal
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000704:Analysis of Variance; D000818:Animals; D003072:Cognition Disorders / Q000201:enzymology* / Q000209:etiology*; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000378:metabolism; D059305:Diet, High-Fat / Q000009:adverse effects*; D004195:Disease Models, Animal; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D018782:Maze Learning / Q000502:physiology; D008568:Memory / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D015999:Multivariate Analysis; D019255:NADPH Oxidases / Q000378:metabolism*; D018384:Oxidative Stress / Q000235:genetics / Q000502:physiology; D011930:Reaction Time / Q000235:genetics; D011971:Receptors, Immunologic / Q000235:genetics; D012891:Sleep Apnea Syndromes / Q000150:complications* / Q000209:etiology*; D013028:Space Perception / Q000502:physiology; D013550:Swimming / Q000523:psychology
C105949:Pirb protein, mouse; D011971:Receptors, Immunologic; D008315:Malondialdehyde; D000080242:8-Hydroxy-2'-Deoxyguanosine; D019255:NADPH Oxidases; D003849:Deoxyguanosine