Relationship between Hippocampal NMDA Receptor together with Associated Synaptic Proteins and Development of Vascular Dementia in Rats / 华中科技大学学报(医学版)

ABSTRACT

Objective To investigate the influence of Memantine on changes of N-methyl-D-aspartic acid receptor 2B (NMDAR-2B) level, the expression of postsynaptic density 95 ( PSD-95) and calcium/calmodulin-dependent protein kinase Ⅱ (CaMK Ⅱ)activities in the hippocampus of vascular dementia(VD)rats and their recognition. Methods The VD rat model was established by permanent,bilateral occlusion of the common carotid arteries. One hundred and forty-four Wistar rats were randomly divided into sham-operated group, VD model group and Memantine-treated group. The water maze test was performed to detect the ability of learning and memory of the rats,the changes of NMDAR-2B level were measured by RT-PCR,the changes in the expression of PSD-95 were detected by immunohistochemical staining,and the changes in the CaMK Ⅱ activities were determined by incorporation of ~(32)P into histone. Results Compared with the sham-operated group, the ability of learning and memory of VD rats was decreased significantly(P<0. 01); the level of NMDAR-2B and the expression of PSD-95 increased significantly at the 4th week after operation(F<0. 05 or 0. 01)and decreased at the 8th to 16th week after operation (P<0. 01). Total CaMK Ⅱ activity was increased significantly at the 4th week after operation(P<0. 01) ,then dropped at the 8th week after operation(P>0. 05) ,and decreased significantly at the 12th,16th week after operation(P<0. 01). As for Memantine-treated group,at the 4th week after operation,there was no statistically significant difference in the parameters mentioned above in contrast with the sham-operated group. At the 8th,and 12th week after operation,the ability of learning and memory,the level of NMDAR-2B and the expression of PSD-95 were significantly increased as compared with VD rats(P<0. 01 or 0. 05) ,but total CaMK Ⅱ activity was similar to that of VD rats. Conclusion With the development of VD,NMDAR-2B level,the expression of PSD-95 and CaMK Ⅱ activities were firstly over-activated,and then decreased greatly. Memantine can improve VD rats' recognition by modulating the expression of NMDAR-2B,but its effect on CaMK Ⅱactivity was limited.