Effect of chronic intermittent hypoxia on memory and CREB expression in growing rats

AIM: To observe the alterations in cognition of growing rats exposed to chronic intermittent hypoxia (CIH) and to explore its underlying mechanisms. METHODS: Forty male Sprague-Dawley rats (3-week-old～4-week-old and 80 g to 100 g), which had been trained to complete the 8-arm (4-arm baited) radial maze, were randomly divided into 4 groups: 2-weeek-CIH group (2IH), 4-week-CIH group (4IH), 2-week-control group (2C) and 4-weeek-control group (4C). The intermittent hypoxia model was induced by putting the animals in an intermittent hypoxia cabin. When intermittent hypoxia was terminated, spatial memory of these growing rats was tested by 8-arm (4-arm baited) radial maze task, then, one rat in each group was randomly selected for ultrastructural observation. The hippocampus and prefrontal cortexes of the rats were collected for analyzing the mRNA and protein expression of CREB by RT-PCR and Western blotting, respectively. RESULTS: (1) In the 8-arm (4-arm baited) radial maze task, the results indicated that the rats in the 4 groups displayed significant difference in their performance assessed by three measuremens: the reference memory error, the working memory error and total memory error (P<0.05, respectively). (2) Early apoptosis and destructure of the neurons in the hippocampus and prefrontal cortex were observed under electron microscope in CIH exposed groups, especially in 4IH group, but not detected in 2C and 4C groups. (3) The expression levels of CREB mRNA and p-CREB protein in 2IH and 4IH groups were less than those in 2C and 4C groups in the hippocampus and prefrontal cortex (P<0.05, respectively), especially in the hippocampus of 4IH group (P<0.01). No difference was found within control groups (P>0.05, respectively). CONCLUSION: Exposure to experimentally-induced IH in growing rats is associated with time related spatial memory impairment. Chronic intermittent hypoxia leads to the disorders of neuron ultra-structure in memory related brain regions. It also inhabits the CREB transduction, expression and CREB phosphorylation, decreases the synthesis of the memory related protein. These factors maybe contribute to learning-memory impairment of growing rats exposed to chronic intermittent hypoxia.