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

Abstract

In 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. IH 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. The 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.

DOI: 10.1186/1471-2202-13-77

Extracted Key Phrases

9 Figures and Tables

Statistics

05010015020132014201520162017
Citations per Year

124 Citations

Semantic Scholar estimates that this publication has 124 citations based on the available data.

See our FAQ for additional information.

Cite this paper

@inproceedings{Dayyat2011ExogenousEA, title={Exogenous erythropoietin administration attenuates intermittent hypoxia-induced cognitive deficits in a murine model of sleep apnea}, author={Ehab A. Dayyat and Shelley X. L. Zhang and Yang Wang and Zixi Cheng and David Gozal}, booktitle={BMC Neuroscience}, year={2011} }