丰富环境介导星形胶质细胞改善慢性脑低灌注大鼠认知功能的机制研究OA

Objective:To explore the effect of environmental enrichment(EE)intervention on cognitive function in chronic cerebral hypoperfusion(CCH)model rats and its potential mechanism.Methods:Thirty-six adult male SD rats were randomly divided into the sham operation group,model group and EE group(n=12 in each group)by computer.The CCH model was established in the model group and EE group by permanent bilateral common carotid artery ligation(2-VO),while the sham operation group only received surgical incision exposure of the vessels without ligation.Three days after the operation,rats in the EE group were subjected to 4 weeks of EE intervention(placed in cages with various toys and facilities at specific times each day),while the other two groups were housed in standard environments.After the environmental intervention,the spatial learning and memory abilities of rats were assessed by Morris water maze.Meanwhile,hippocampal GFAP(astrocyte marker)and LCN2 expressions were detected by immunofluorescence double labeling;and BDNF protein by Western blot.Results:The results of Morris water maze place navigation experiment showed that the escape latency of rats in all three groups significantly decreased with the increase of training days(P<0.05),but there were significant differences among the groups(P<0.05).The latency of model group and EE group on the 2nd to 5th day was longer than that of sham operation group(P<0.05),but the latency of EE group was significantly shorter than that of the model group(P<0.05).In the spatial exploration test,the swimming distance,swimming time and the number of times crossing the original platform in the target quadrant of model group and EE group rats were less than those of sham operation group(P<0.05).However,the above indicators in EE group were significantly higher than those in model group(P<0.05).Immunofluorescence showed that the expression levels of GFAP and LCN2 in reactive astrocytes in the hippocampus of the model group were significantly higher than those of the sham operation group and EE group(P<0.05).There was no significant difference in the expression of GFAP and LCN2 between the sham operation group and the EE group(P>0.05).Western blot analysis indicated that there were significant differences in BDNF protein expression in the CA1 region of the hippocampus among the groups(P<0.05).The BDNF content in the model group was lower than that in the sham operation group(P<0.05),while EE intervention significantly upregulated the BDNF content compared with the model group(P<0.05).Conclusion:EE intervention can effectively improve cognitive dysfunction in CCH rats,and its mechanism may be related to the inhibition of astrocyte activation in the hippocampus(as evidenced by reduced GFAP expression),down-regulation of LCN2 expression,and promotion of BDNF protein expression.