Effect of environmental enrichment on cognitive function and the expressions of hypoxia inducible factor 1α and vascular endothelial growth factor in rats with chronic cerebral hypoperfusion / 中华老年医学杂志

ABSTRACT

Objective To observe effect of environmental enrichment on the learning and memory ability and the expressions of hypoxia inducible factor 1α (HIF-1a) and vascular endothelial growth factor (VEGF) in rats with chronic cerebral hypoperfusion.Methods A total of 40 rats were randomly divided into 3 groups bilateral vascular occlusion (2VO) of the common carotid arteries group (n=14, 2VO group), 2VO + enriched environment (EE) group (n=14, 2VO+EE group) and sham group (n=12, SHAM group).Morris water maze, novel object recognition test, real-time reverse transcription-polymerase chain reaction (real-time RT-PCR), immunohistochemistry methods and Western blotting were used to detect changes in learning and memory ability of rats and HIF-1α and VEGF expression levels in hippocampus.Results Morris water maze showed that the escape latency was longer in the 2VO group than in the SHAM group at 3, 4 and 5 day during the training (all P＜0.05), while the 2VO+EE group spent significantly less time in finding the platform as compared with the 2VO group at 4 and 5 day (both P＜0.05).The time for space exploration in target quadrant was less in 2VO group than in SHAM group (P＜0.05), while it was longer in 2VO +EE group than in 2VO group (P＜0.05).Novel object recognition test showed that the 2VO operation impaired the priority index (PI) of time spending at exploring the novel object (P＜0.05), and environmental enrichment could improve the PI in 2VO group (P＜0.05).The real-time RT-PCR and Western blotting showed that the HIF-1α mRNA expression was higher in 2VO group than in SHAM group (P＜0.05).The VEGF mRNA and protein expressions were higher in 2VO+EE group than in 2VO group (both P＜0.05).The expression of HIF-1α in hippocampal CA1 area was higher in 2VO group than in SHAM group (P＜0.05).Conclusions Environmental enrichment can alleviate the damages of spatial and non-spatial learning and memory ability which are caused by chronic cerebral hypoperfusion.And HIF-1α and its downstream gene VEGF may be involved in the restoration of cognitive function by enriched environment.