Relationship of learning and memory impairment in chronic intermittent hypoxic rats with hippocampus ERK activation and microtubule-associated protein 2 expression

Objective: To investigate the relationship of the learning and memory function with ERK signaling pathway changes and microtubule-associated protein-2 (MAP-2) expression in hippocampal CA1 region of intermittent hypoxic rats. Methods: The chronic intermittent hypoxia rat model was established; 96 mature male wistar rats were randomly divided into three groups: normal air (control) group, 5% intermittent hypoxia (5% IH) group and the intervention (5% IH U0126) group; homemade hypoxic chamber was used to simulate 5% chronic intermittent hypoxia model; exposure time was 8 h/d, continuing 28 d; after modeling, learning and memory behaviors of the rats were detected by Morris water maze test at four time points (7, 14, 21, 28 d); P-ERK1/2 and MAP-2 protein expression in hippocampal CA1 region was detected by immunohistochemistry. Results: Compared with the control group, escape latencies at 14, 21, 28 d in 5% IH group were increased significantly (P<0.05); from 14 d, with prolonged hypoxia time, escape latency prolonged (P<0.05); and the time of rats crossing the target quadrant was shortened (P<0.05). In the intervention group escape latency time at 7, 14, 21, 28 d was similar to the 5% IH group. Compared with the intervention group, 5% IH group changed more obviously (P<0.05). Immunohistochemistry results showed that, in 5% IH group, P-ERK1/2 protein expression levels in hippocampal CA1 region at 7, 14, 21, 28 d were significantly higher than those in control group (P<0.05). In the intervention group, P-ERK1/2 protein expression levels at 7, 14, 21, 28 d showed no significant difference compared with the control group (P>0.05). However, compared to control group, MAP-2 protein expression levels were reduced significantly both in 5% IH group and in the intervention group. Conclusion: Chronic intermittent hypoxia can lead to learning and memory dysfunction in rats, activate ERK pathway in rat hippocampus, and induce MAP-2 protein degradation. Chronic intermittent hypoxia leading to reduced levels of learning and memory in rats may be associated with reduced MAP-2 levels in the hippocampus.