Effects of memantine on lipopolysaccharide-induced spatial learning and memory impairment in C57BL/6J mice / 医学研究生学报

ABSTRACT

[Abstract ] Objective The pathogenesis underlying cognitive dysfunction has yet to be fully elucidated.The article was to investigate the effects of memantine on lipopolysaccharide (LPS)-induced spatial learning and memory impairment in C57BL/6J mice. Methods 36 male C57BL/6J mice were randomly divided into 3 groupscontrol group (C group), lipopolysaccharide group (L group) and memantine group (M group) (n=12).Mice in C, L and M groups were intraperitoneally injected with the same volume of saline, LPS and LPS plus memantine re-spectively for 7 consecutive days.On the 8th day, mice were tested in the Morris water maze, in which the latency to the platform and the propor-tion of time spent in the target quadrant were recorded .Then the mice were sacrificed and the hippocampi were harvested for the determination of expression levels of Amyloid-β(Aβ), glycogen synthase kinase-3β(GSK-3β) and mammalian target of rapamycin (mTOR). Results Com-pared with C group, L group significantly prolongated the latency to the platform (71.01 ±13.21 vs 50.56 ±9.89, P<0.05), decreased the propor-tion of time spent in the target quadrant (42.58 ±7.85 vs 63.74 ±12.43, P<0.05) and increased the levels of hippocampal Aβand GSK-3β(1.75 ±0.43 vs 1.27 ±0.23, 184.0 ±18.6 vs 100.0 ±12.1, P<0.05), (75.0 ±13.5 vs 100.0 ±10.3, P<0.05), while mTOR levels decreased significantly (97.0 ±14.3 vs 75.0 ±13.5, P<0.05).Compared with L group, M group significantly prolongated the latency to the platform (61.45 ±7.65 vs 71.01 ±13.21, P<0.05), decreased the proportion of time spent in the target quadrant shortened (58.25 ±9.02 vs 42.58 ±7.85, P<0.05) and increased the expression of hippocampal Aβ(1.35 ±0.28 vs 1.75 ±0.43,92.4 ±10.8 vs 184.0 ±18.6, P <0.05). Conclusion Memantine contributes to the improvement of LPS-induced spatial learning and memory impairment, which is probably related to the changes of the expression of GSK-3βand mTOR in hippocampus.