title: Endoplasmic reticulum stress plays critical role in brain damage after chronic intermittent hypoxia in growing rats.
abstract: 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 4weeks 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.
authors.affiliation: Department of Pediatrics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325027, China; Institute of Hypoxia Medicine, Wenzhou Medical University, Wenzhou 325000, China. Electronic address: caixh839@sina.com.
authors.forename: Xiao-Hong
authors.initials: XH
authors.lastname: Cai
authors.affiliation: Department of Pediatrics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325027, China.
authors.forename: Xiu-Cui
authors.initials: XC
authors.lastname: Li
authors.affiliation: Department of Anesthesia and Critical Care, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325027, China.
authors.forename: Sheng-Wei
authors.initials: SW
authors.lastname: Jin
authors.affiliation: Department of Pediatrics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325027, China.
authors.forename: Dong-Shi
authors.initials: DS
authors.lastname: Liang
authors.affiliation: Department of Pediatrics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325027, China.
authors.forename: Zheng-Wang
authors.initials: ZW
authors.lastname: Wen
authors.affiliation: Department of Pediatrics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325027, China.
authors.forename: Hong-Chao
authors.initials: HC
authors.lastname: Cao
authors.affiliation: Department of Pediatrics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325027, China.
authors.forename: Hong-Fang
authors.initials: HF
authors.lastname: Mei
authors.affiliation: Scientific Research Centre, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325027, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Department of Pediatrics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325027, China. Electronic address: wzlzhd@wzhealth.com.
authors.forename: Zhong-Dong
authors.initials: ZD
authors.lastname: Lin
authors.affiliation: Department of Pulmonology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China. Electronic address: 38805@163.com.
authors.forename: Liang-Xing
authors.initials: LX
authors.lastname: Wang
mesh_terms: D000367:Age Factors; D000375:Aging; D000818:Animals; D001794:Blood Pressure; D001930:Brain Injuries / Q000097:blood / Q000209:etiology*; D002934:Cinnamates / Q000494:pharmacology; D004195:Disease Models, Animal; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism*; D059865:Endoplasmic Reticulum Stress / Q000502:physiology*; D006624:Hippocampus / Q000473:pathology; D000860:Hypoxia / Q000097:blood / Q000150:complications*; D007859:Learning Disabilities; D008297:Male; D018782:Maze Learning / Q000502:physiology; D009842:Oligopeptides / Q000235:genetics / Q000378:metabolism; D017397:Prefrontal Cortex / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013890:Thiourea / Q000031:analogs & derivatives / Q000494:pharmacology; D013997:Time Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: C539791:Bax-inhibiting peptide, BIP; D002934:Cinnamates; D009842:Oligopeptides; D014157:Transcription Factors; C496827:salubrinal; D013890:Thiourea
keywords: Apoptosis; C/EBP-homologous protein; Chronic intermittent hypoxia; Cognition dysfunction; Endoplasmic reticulum stress; Inositol-requiring enzyme l; PKR-like endoplasmic reticulum (ER) kinase; Salubrinal