Exogenous erythropoietin administration attenuates intermittent hypoxia-induced cognitive deficits in a murine model of sleep apnea

BMC Neuroscience

Research Article

Zixi Jack Cheng¹  David Gozal²  Shelley X Zhang²  Yang Wang²  Ehab A Dayyat² 

[1] Biomolecular Science Center, Burnett College of Biomedical Sciences, University of Central Florida, Orlando, FL, USA;Department of Pediatrics, Pritzker School of Medicine, Comer Children’s Hospital, The University of Chicago, 5721 S. Maryland Avenue, Suite K-160, MC 8000, Chicago, IL, USA;

关键词: Obstructive Sleep Apnea;    NADPH Oxidase;    Force Swimming Test;    Intermittent Hypoxia;    Chronic Intermittent Hypoxia;   

DOI  :  10.1186/1471-2202-13-77

 received in 2011-11-05, accepted in 2012-06-18,  发布年份 2012

来源: Springer

【 摘 要 】

BackgroundIn rodents, exposure to intermittent hypoxia (IH), a hallmark of obstructive sleep apnea (OSA), is associated with neurobehavioral impairments, increased apoptosis in the hippocampus and cortex, as well as increased oxidant stress and inflammation. Such findings are markedly attenuated in rodents exposed to sustained hypoxia 9SH) of similar magnitude. The hypoxia-sensitive gene erythropoietin (EPO) has emerged as a major endogenous neuroprotectant, and could be involved in IH-induced neuronal dysfunction.Methods and ResultsIH induced only transiently increased expression of EPO mRNA in hippocampus, which was continued in (SH)-exposed mice. IH, but not SH, adversely affected two forms of spatial learning in the water maze, and increased markers of oxidative stress. However, on a standard place training task, mice treated with exogenously administered EPO displayed normal learning, and were protected from the spatial learning deficits observed in vehicle-treated (C) littermates exposed to IH. Moreover, anxiety levels were increased in IH as compared to normoxia, while no changes in anxiety emerged in EPO-treated mice. Additionally, C mice, but not EPO-treated IH-exposed mice had significantly elevated levels of NADPH oxidase expression, as well as increased MDA and 8-OHDG levels in cortical and hippocampal lysates.ConclusionsThe oxidative stress responses and neurobehavioral impairments induced by IH during sleep are mediated, at least in part, by imbalances between EPO expression and increased NADPH oxidase activity, and thus pharmacological agents targeting EPO expression in CNS may provide a therapeutic strategy in sleep-disordered breathing.

【 授权许可】

Unknown   
© Dayyat et al.; licensee BioMed Central Ltd. 2012. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.