Effect of atorvastatin on ADAM10 in hippocampus of chronic cerebral hypoperfusion in rats

Abstract

Objective To investigate the learning and memory functions, expression changes of disintegrin and metalloprotease 10 （ADAM10） mRNA in hippocampus in the aged rats with chronic cerebral hypoperfusion as well as the effect of atorvastatin on them. Methods A total of 72 rats were randomly divided into sham operation, cerebral hypoperfusion and atorvastatin treatment groups. A permanent bilateral common carotid artery occlusion （2VO） model was induced. Atorvastatin 10 mg/（kg · d） was administered orally after procedure in the atorvastatin treatment group. Real-time fluorescence quantitative polymerase chain reaction was used to detect the expression of ADAM10 mRNA in bilateral hippocampus at 1, 2, 4, and 16 weeks after modeling, Results Two weeks after modeling, the learning and memory functions were decreased significantly in the cerebral hypoperfusion group compared to the sham operation group （P 〈 0. 05）. At 4 and 16 weeks after modeling, they were further decreased （P 〈 0. 01）; there were no significant differences in the learning and memory functions at 1, 2, and 3 weeks after modeling between the atorvastatin treatment group and the cerebral hypoperfusion group, however, they were improved significantly at 16 weeks compared to the cerebral hypoperfusion group （P〈 0. 01）. The expression of ADAM10 mRNA in hippocampus at different time points after modeling in the cerebral hypoperfusion group was down-regulated by 22%, 43%, 35%, and 50%, respectively compared to the sham operation group （all P 〈0. 05）. The expression of ADAM10 mRNA in hippocampus at 2 weeks in the atorvastatin treatment group was higher than 22% in the cerebral hypoperfusion group （P 〈 0. 05）. There were not significant differences at other time points. Conclusions Chronic cerebral hypoperfusion results in the down-regulation of the expression of ADAM10 mRNA in hippocampus in the aged rats, and atorvastatin may inhibit down-regulation of the expression of ADAM10 mRNA at early stage. Key words: Brain ischemia; ADAM proteins; Amyloid precursor protein seeretases; Metalloendopeptidases; Amyloid β-peptides; Hydroxymethylglutaryl-CoA reductase inhibitors; Atorvastatin; Hippocampus; Rats