期刊
EXPERIMENTAL NEUROLOGY
卷 257, 期 -, 页码 148-156出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.expneurol.2014.04.029
关键词
Chronic intermittent hypoxia; Endoplasmic reticulum stress; Cognition dysfunction; Salubrinal; PKR-like endoplasmic reticulum (ER) kinase; Inositol-requiring enzyme 1; C/EBP-homologous protein; Apoptosis
资金
- Zhejiang Province Science and Technology Grant [200803011, 201303174]
- Natural Science Foundation of Zhejiang Province [Y2110277]
- Wenzhou City Science and Technology Bureau Grant [Y20080083, H20130001]
- Scientific Research Foundation of Health Bureau of Zhejiang Province [2011RCB027, 2014ZDA014]
- Project of National Key Clinical Subspeciality from the Ministry of Health of the People's Republic of China
Obstructive sleep apnea hypopnea syndrome (OSAHS) in children is associated with multiple system morbidities. Cognitive dysfunction as a result of central nervous system complication has been reported in children with OSAHS. However, the underlying mechanisms are poorly understood. Endoplasmic reticulum stress (ERS)-related apoptosis plays an important role in various diseases of the central nervous system, but very little is known about the role of ERS in mediating pathophysiological reactions to cognitive dysfunction in OSAHS. Chronic intermittent hypoxia (CIH) exposures, modeling OSAHS, across 2 and 4 weeks in growing rats made more reference memory errors, working memory errors and total memory errors in the 8-Arm radial maze task, increased significantly TUNEL positive cells, upregulated the unfolded protein response in the hippocampus and prefrontal cortex as evidenced by increased phosphorylation of PKR-like endoplasmic reticulum kinase, inositol-requiring enzyme l and some downstream products. A selective inhibitor of eukaryotic initiation factor-2a dephosphorylation, salubrinal, prevented C/EBP-homologous protein activation in the hippocampus and prefrontal cortex throughout hypoxia/reoxygenation exposure. Our findings suggest that ERS mediated cell apoptosis may be one of the underlying mechanisms of cognitive dysfunction in OSAHS children. Further, a specific ERS inhibitor Salubrinal should be tested for neuroprotection against CIH-induced injury. (C) 2014 Published by Elsevier Inc.
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