| Abstract:Objective explore the role of endoplasmic reticulum stress in cognition dysfunction following chronic intermittent hypoxia (IH) in growing rats. Methods a total of 32 healthy male SD rats (3-4-week-old, 100-120g), were randomly assigned to four groups:intermittent hypoxia 2 and 4 weeks group (2IH, 4IH), control 2, 4 weeks group (2C, 4C), with 8 rats in each group. The eight arm maze test was used to record the memory errors, including working memory errors (WME), reference memory errors (RME) and total errors (TE). The changes of neuronal apoptosis in hippocampus were observed by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining. And the expressions of endoplasmic reticulum stress marker compounds, immunoglobulin binding protein (BIP), activation of transcription factor 4 (ATF4), C/EBP homologous protein (CHOP) and phosphorylation of RNA activated protein kinase of endoplasmic reticulum like kinase (p-PERK) were analyzed by quantitative PCR and western blotting. Results Chronic intermittent hypoxia caused more WME, RME and TE in growing rats, especially in the 4IH group (2IH group vs 4H group, WME:3.38±0.52 vs 2.12±0.84; RME:4.25±0.71 vs 3.00±0.93; TE:7.62±0.74 vs 5.12±0.64, all P<0.01). IH increased significantly TUNEL positive cells in the hippocampus, more obviously in the 4IH group (2IH group vs 4H group, 20.78%±2.63% vs 14.94%±1.59%, P<0.01), upregulated p-PERK and CHOP protein, especially in the 4IH group (p-PERK:3.72±0.21 vs 1.85±0.07; CHOP:4.29±0.27 vs 2.69±0.11, all P<0.01). Comepared with the control groups, the mRNA expression of BiP, ATF4 and CHOP in IH groups were upregulated, and ATF4 and CHOP mRNA expression in 2IH groups were more than that in 4IH groups (ATF4:3.5±0.24 vs 1.92±0.13, P<0.01; CHOP:3.09±0.22 vs 1.95±0.18, P<0.01). Conclusion Chronic intermittent hypoxia can upregulate the expression of BiP, ATF4, p-PERK and CHOP in the hippocampus, memory-related brain area. Our findings suggest that endoplasmic reticulum stress induced cell apoptosis, and PERK/ATF4/CHOP may play an important role in brain injury. |
