Endoplasmic reticulum stress plays critical role in brain damage after chronic intermittent hypoxia in growing rats
Autor: | Dongshi Liang, Mei Hongfang, Zhong-Dong Lin, Ying Wu, Xiao-Hong Cai, Shengwei Jin, Liang-Xing Wang, Xiu-Cui Li, Zhengwang Wen, Cao Hongchao |
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Rok vydání: | 2013 |
Předmět: |
Male
medicine.medical_specialty Aging Time Factors Prefrontal Cortex Blood Pressure Brain damage Biology Endoplasmic Reticulum Neuroprotection Hippocampus Salubrinal Rats Sprague-Dawley chemistry.chemical_compound Developmental Neuroscience Internal medicine medicine Animals ASK1 Prefrontal cortex Hypoxia Maze Learning Learning Disabilities Endoplasmic reticulum Age Factors Thiourea Hypoxia (medical) Endoplasmic Reticulum Stress Rats Disease Models Animal Endocrinology Neurology chemistry Cinnamates Brain Injuries Unfolded protein response medicine.symptom Oligopeptides Transcription Factors |
Zdroj: | Experimental neurology. 257 |
ISSN: | 1090-2430 |
Popis: | 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. |
Databáze: | OpenAIRE |
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