| Background:Alzheimer's disease (AD) and vascular dementia (VaD) are the two most common types of dementia, chronic cerebral hypoperfusion is the important pathologic basis for both of them. It's extremely necessary to explore the intervention paradiam of improving the cognitive impairment induced by chronic cerebral hypoperfusion (CCH) and its possible underlying mechanism. As a behavioral intervention paradiam, Enriched environment (EE) has drawn more and more attention in the experimental study of cognitive neuroscience in recent years. A large number of studies have demonstrated the beneficial effects of EE on brain structure and function, especially in modifying the behaviors, particularly in tasks involving complex cognitive functions. However, the impacts of EE on cognitive impairment induced by chronic cerebral hypoperfusion (CCH) and the underlying molecular mechanisms have not been studied. In present study, we investigated the effects of EE on cognitive impairment caused by CCH and examined whether CCH altered the protein levels of brain-derived neurotrophic factor (BDNF),N-methyl-D-aspartate (NMDA) receptor subunit 1 (NR1) and subunit 2B (NR2B), insulin like growth factor-1 (IGF-1) and vascular endothelial growth factor (VEGF) in the hippocampus of rats and whether EE exposure attenuated the effects.Objects:To explore whether EE can improve the cognitive impairment induced by CCH and its possible underlying molecular mechanisms.Methods:Wistar Rats were divided into four groups(sham+SE; 2-VO+SE; sham+EE; 2-VO+EE) that received either permanent bilateral ligation of the common carotid arteries (2-vessel occlusion,2-VO) surgery or sham surgery. Four weeks later, the groups were supplied either EE housing or standard environment (SE) housing for 4 weeks. EE paradiam was designed as described by Nithianantharajah and Hannan. Then all the rats were examined non-spatial recognition memory in the novel object recognition task, spatial learning, and memory ability in the Morris water maze as well as the protein levels of BDNF, NR1, NR2B,IGF-1 and VEGF in the hippocampus.Results:(1) in the object recognition task, regarding the two groups housed in SE, the rats of sham group spending the time in the exploration of novel objects was significantly more than the time of exploration of familiar objects, while the rats of 2-VO group spent almost equal time in the exploration of both objects; The discrimination rate of novel objects were significantly higher than chance in the rats of either 2-VO group and sham group treated by EE, as well as the rats of sham group housed in SE. (2) On the training period of 4 to 5 days in Morris water maze test, the rats of 2-VO group housed in SE spending the time to find the platform was significantly longer than the the rats of sham group, and the rats of 2-VO group treated by EE spending the time to find the platform was significantly less than the rats of 2-VO group housed in SE; Regarding the rats of sham groups, on the training period of 2 to 4 days, the group treated by EE spending the time to find the platform was significantly less than the group housed in SE, and in the space exploration test, the group treated by EE also spending the time in the target quadrant was significantly more than the group housed in SE. (3) The BDNF and NR1 protein levels of 2-VO rats housed in SE were significantly decreased compared with the sham control group, while the BDNF and NR1 protein levels of 2-VO rats treated by EE were significantly increased compare with their counterparts housed in SE; the protein levels of NR2B, IGF-1 and VEGF in each group showed no significant difference.Conclusion:EE exposure can restore cognitive impairment induced by CCH and up-regulates the decreased protein levels of BDNF and NR1. Inversely, BDNF and NR1 may contribute to the beneficial effects of EE on CCH in rats. |
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