| Objective:To observe the effects of alpha-asarone on the learning and memory ability of mice with mild cognitive impairment,and to study its mechanism from the perspective of glutamate and gamma-aminobutyric acid neurotransmitter equilibrium.Methods:The healthy male C57BL/6J mice were randomLy divided into six groups:solvent control group,memory demaged model group,alpha-asarone treatment groups,and rolipram group.The memory demaged model group was reproduced by means of gastric anhydrous ethanol.New object recognition experiment was used to evaluate the learning and memory ability of mice;High performance liquid chromatography,Glu and GABA kit were used to determine the contents of Glu and GABA in the hippocampus;Western blot was used to detect the phosphorylated leves of SynapsinI?SYNI?,calmodulin dependent protein kinase?CaMK??,glutamate transporter1?GLT-1?,N-methyl-D-aspartate receptor?NMDAR?and?-amino-3-hydroxy-5-methyl-4-isox azole-propionic acid receptor?AMPAR?.Results:1.The determination of memory demaged model success:The behavior of solvent control group and memory impairment group were tested by new object recognition experiment.The results showed that solvent control group mice had less exploration behaviors such as olfactory and touch,and spent a long time exploring new object.In the memory impairment group,there was more exploration of old objects,almost no exploration of new objects.It was Indicated that the solvent control groupremembered the old familiar object.The model mice did not remember old object.The object recognition index of the model group was significantly lower than that of the solvent control group and the model was considered to be successful.2.The behavioral effect on mice with memory impairment group by?-Asarone:Compared with solvent control group,object recognition index of model group had a significantly decrease.(***P<0.001),compared with memory impairment group,?-Asarone treatment groups could significantly improve the object recognition index of mice(#P<0.05,##P<0.01,###P<0.001),indicating that?-asarone on mild cognitive dysfunction mice learning can significantly improve cognitive ability.3.The content of Glu and GABA in tissues with high performance liquid-fluorescence assay:Compared with the solvent control group,the ratio of Glu/GABA in tissues?0.157±0.008 vs 0.393±0.047?increased significantly(***P<0.001).Compared with memory impairment model group,group of alpha-asarone low-dose?0.345±0.024 vs 0.393±0.047?,he medium dose administration group?0.317±0.039vs 0.393±0.047?,a group of high dose?0.248±0.016 vs 0.393±0.047?,rolipram trearment?0.219±0.025 vs 0.393±0.047?and each dose group could significantly reduce the ratio of Glu/GABA in group(#P<0.05,##P<0.01).4.Determination of Glu and GABA in serum:Compared with solvent control group,the ratio of Glu/GABA in serum?5076±32.31 vs 4902±17.44?was significantly increased(***P<0.001).Compared with the model group,the low-dose group?5017±50.83 vs 5076±32.31?,and the medium dose administration group?5012±0.89 vs 5076±32.31?,and the high dose administration group?4994±29.28vs 5076±32.31?,rolipram trearment?5015±22.46 vs 5076±32.31?.It could significantly reduce the ratio of Glu/GABA in tissue and serum(#P<0.05,##P,<0.01###P<0.001).5.The results of Western blot:Compared to solvent control group,the level of phosphorylated SYNI protein and CaMKII protein increased significantly in the hippocampus of model group(***P<0.001).GLT-1 protein expression significantly reduced(**P<0.01),the level of phosphorylated GluR2 protein and NMDAR2B protein showed significantly increased(**P<0.01,***P<0.001).Compared with model group,medication administration group could significantly reduce the phosphorylated expression of SYNI?CaMKII?GluR2 and NMDAR2B(#P<0.05,##P<0.01,###P<0.001).The expression of GLT-1 could significantly enhance?#P<0.05?.Conclusion:Alpha-asarone could significantly improve learning cognitive ability in MCIl mice,its mechanism might be related to adjust the Glu and GABA neurotransmitter balance. |
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