Effect Of Compound Chinese Medicine SM Ⅰ On Learning And Memory Dysfunction In Mice And Its Mechanism

OBJECTIVE:The goal of this study is to investigate the effect of traditional Chinese medicine compound SM I on learning and memory ability in memory disorder mice and its possible mechanisams and provide experimental data for clinic utilization of compound SM. METHODS:1. The memory disorder mice were induced by scopolamine, sodium nitrite and alcohol and step down test was used to examine the function of learning and memory in memory disorder mice. The cholinesterase activity in brain tissue of memory acquired disorder mice induced by scopolamine was mearsured. 2. The mice were treated with D-galactose and AlCl3 to establish the AD animal model. D-galactose was given through intraperitoneal route for 62 days and AlCl3 was given through intragastric route for 106 days. Since the 67th day, the SM I group was treated with low dose SM I which had been tested the most effectively. The SM I treatment continued for 40 days. Subsequently, the water maze test was applied to evaluate the effect of SM I on the AD model mice. After the last test day, the animals were killed and brain tissues were separated from cranial cavity. The cholinesterase activity in cerebral cortex of AD mice was detected. The expressions of brain-derived neurotrophic factor (BDNF) by reverse transcription polymerase chain reaction (RT-PCR) and expressions of CREB/pCREB in mice hippocampus by immunohistochemistry staining were observed. RESULTS:1. Compound SM I decreased the total electric shock time in memory acquisition disorder mice (P<0.05). SM I group had longer latency and less error times in memory test in memory consolidation disorder mice (P<0.05). In memory retention disorder mice, SM I group had less error times (P<0.05). SM I decreased the brain cholinesterase activity in memory acquisition disorder mice induced by scopolamine (P0.05). 2. By oral administration with SM , mice had shorter latency (P<0.01) and less error times (P<0.05) in water maze test and decreased AChE activities in cerebral cortex comparedwith AD model. In addition, the expression of BDNF was upregulated (P<0.01) and immunohistochemistry staining showed higher phosphorylation of CREB in hippocampus (P<0.01), while the expression of CREB had no difference (P>0.05). CONCLUSIONS:1. Low dose compound SM I improved the learning ability of memory acquired disorder mice. 2. Low, middle and high doses SM I improved the memory ability of memory consolidation disorder mice. 3. All the three doses of SM I improved the memory ability of memory retention disorder mice. 4. SM I improved the learning and memory ability of AD model mice and was better than piracetam. 5. The mechanism may be related to the decreased activity of AChE, the upregulated expression of BDNF and increased phosphorylation of CREB.