Effects of treadmill training on remyelination in hippocampus and cognitive function in rats exposed to acute plateau hypoxia

Abstract

Objective To determine the effects of treadmill training on the structure of hippocampal myelin and cognitive function in rats exposed to acute plateau hypoxia. Methods With 30 SPF-grade female SD rats (aged 6-8 weeks, weighing 200-220 g), 6 of them were used for observation of myelin structure after injury, and the remaining 24 rats were randomly divided into control group, hypobaric hypoxia group and treadmill training group (n=8). The rats in above experimental groups were placed in a low-pressure oxygen chamber at an altitude of 6 000 m for 7 consecutive days, and the rats of the control group were placed in the confined chamber for the same period without hypoxia. Then, the rats of the treadmill training group received a 4-week treadmill training scheme since the day after hypoxia. Finally, all the rats were tested for cognitive function with open field test (OFT) and Morris water maze (MWM). Transmission electron microscopy (TEM) was used to observe the changes of demyelination in the hippocampus. The expression of oligodendrocyte transcription factor 2 (Olig2) and myelin basic protein (MBP) in the hippocampal CA1 and CA3 regions was measured by immunofluorescence staining and Western blotting. Results Behavioral tests showed that the number into the central area, total distance, distance ratio in OFT and the number of platform crossings and distance to the target area in MWM were reduced in the hypobaric hypoxia group than the control group (P < 0.05), while these indexes were increased in the treadmill training group than in the hypobaric hypoxia group (P < 0.05). Immunofluorescence staining indicated that the number of Olig2 positive cells per unit area and the mean fluorescence intensity of MBP in the CA1 and CA3 regions were significantly lessen in the hypobaric hypoxia group than the control group (P < 0.05), while these indicators were higher in the treadmill training group than the hypobaric hypoxia group (P < 0.05). Western blotting displayed that the expression levels of Olig2 and MBP in the hippocampus were obviously lower in the hypobaric hypoxia group than the control group (P < 0.01), while the levels were increased in the treadmill training group than the hypobaric hypoxia group (P < 0.01). Conclusion Treadmill training promotes the number of the oligodendrocyte spectrum cells in CA1 and CA3 regions, enhances the expression of myelin-related proteins and improves myelin repair in hippocampus of hypobaric hypoxia rats, and thereby ameliorates hypoxia-induced anxiety-like behaviors and memory dysfunction.

Keywords

• hypobaric hypoxia
• treadmill training
• myelin regeneration
• cognitive function