The Effect And The Underlying Mechanism Of Memantine On The Learning And Memory Ability In Vascular Dementia Rats

Objective To investigate the effect and underlying mechanism of memantine on N-methy-Daspartate receptor(NMDAR) and brain-derived neurotrophic factor(BDNF) in rats with ischemic vascular dementia(Va D). To analyze the mechanism of the learning and memory improvement, indicated by the long-term potentiation(LTP), the BDNF and different NMDAR subunits expression in the hippocampus.Methods Thirty adult male SD rats were equally randomized into sham operation group, Va D model group and memantine group, 10 for each group. The two-vessel occlusion(2-VO) mothod was used to establish the model of Va D. Memantine[10mg/(kg·d)] was administered orally to the memantine group, one week after 2-VO operation for 28 consecutive days. The same volume of saline was administered orally to the Va D model group. Five weeks after the operation, the ability of spatial learning and memory was assessed with the Morris water maze including the average escape latency and the percentage of target quadrant. Then the CA3-CA1 LTP was measured. The pathologic changes of nerve cells in the hippocampus were observed by hematoxylin and eosin stain. The expression of BDNF and NMDAR subuints was analyzed by Western blotting. The expression of BDNF and NR1 in the hippocampus was also observed by immunohistochemistry.Results Compared with the sham group, the average escape latency was greatly prolonged(P<0.05), the percentage of target quadrant was significantly decreased(P<0.05). The CA3-CA1 LTP of Va D group was greatly damaged. Memantine could enchance CA3-CA1 LTP. The expression of BDNF, NR1, NR2 A and NR2 B of Va D model group were significantly decreased compared with the sham group. In the contrary, the expression of NR2 D was greatly increased compared with the sham group. Compared with the model group, memantine can not only significantly upregulate the expression BDNF, NR1, NR2 A and NR2 B, but also decline the expression of NR2 D. Memantine have no effect on NR2 C. The morphology of nerve cells in the hippocampus in Va D group are disordered and damaged obviously.Conclusions Memantine at adequate dosage could improve the learning and memory ability in the vascular dementia rats by modulating the expression of BDNF, NR1, NR2 A, NR2 B and NR2 D. Synaptic plasticity could be enchanced by memantine. The formation of LTP is associated with BDNF, NR1, NR2 A and NR2 B in the hippocampus. Memantine improved the spatial learning and memory of the Va D rats through the BDNF-NMDAR dependent LTP.