| Objective: To observe the effect of Tetrahydroxy stilbene glucoside(TSG)on learning and memory abilities,the pathomorphological changes in hippocampus,the expression levels of amyloid precursor protein(APP),β-amyloid precursor protein cleavage enzyme 1(BACE1),Presenilin 2(PS-2)and cysteiny aspartate specific protease-3(caspase-3)proteins in brain tissues of APP/ Presenilin 1(PS1)double transgenic mouse model of Alzheimer’s disease(AD),and aimed to investigate the possible mechanisms of therapeutical effect about TSG on AD.Methods: Sixty three-months-old APP/PS1 double transgenic mice were randomly divided into low-dose TSG group,mid-dose TSG group,high-dose TSG group,a huperzine A(positive control)group and an APP/PS1 model group with twelve mice in each based on the random number table.Another twelve three-months-old C5B7L/6J mice were assigned to the normal control group.Low,mid-and high-dose TSG groups,huperzine A group,model group and normal control group were respectively given by gavage with TSG 0.033,0.1,0.3g/kg,huperzine A(0.02 mg/kg),0.9% sodium chloride solution(10ml/kg),0.9% sodium chloride solution(10ml/kg),once a day,for 60 days.At the end of intervention,all the mice were sacrificed and the brain tissues were taken out for experiments.Morris water maze test was used to assess each group mice’s learning and memory abilities;HE staining was used to observe the pathomorphological changes in hippocampus of each group mice;Western blot was used to detect the expression levels of APP,BACE1 and PS-2 proteins in each group mice’s brain tissues;Immunohistochemical method was used to detect the number of caspase-3 positive cells in each group mice’s cerebral cortex and hippocampus.Results:(1)Compare with normal control group,the mice of model group showed significant impairments in learning and memory in Morris water maze test,its escape latency and reverse platform latency were longer than that of normal control group(P<0.01),and its time and times of swim in original platform quadrant were less than that of normal control group(P<0.01).From the third training day,TSG-treated groups and huperzine A group mice’s escape latency were significantly shorter than that of model group(P<0.01),and from the first training day,their reverse platform latency were obviously shorter than that of model group too(P<0.01 or P<0.05),their time of swim in original platform quadrant were significantly longer than that of model group(P<0.01),and their times of crossing the original platform were obviously more than that of model group(P<0.01 or P<0.05).After mice adaptation training,the escape latency,the reverse platform latency and the time and times of swim in original platform quadrant of the mice in TSG-treated groups was not significantly different from that of mice in the huperzine A group(P>0.05).The results among each group in visual platform test had no significant difference(P>0.05).(2)The neurons number in hippocampus of mice in the model group was less than this in the normal control group,and the neurons were irregular arrangement as well.Compare with model group,the hippocampal pathomorphological configurations of the mice in TSG-treated groups and huperzine A group were recovered at different degree.(3)The expression levels of APP,BACE1 and PS-2 proteins in brain tissues of mice in the model group were significantly higher than those in the normal control group(P<0.01).The mice in normal control group,TSG groups and huperzine A group had lower expression levels of APP,BACE1 and PS-2 proteins in brain tissues than those in the model group(P<0.01).The expression levels of APP,BACE1 and PS-2 proteins in brain tissues of the mice in TSG-treated groups did not differ substantially from those of mice in the huperzine A group(P>0.05).(4)The number of caspase-3 positive cells in cerebral cortex and hippocampus of mice in the model group were significantly more than those in the normal control group(P<0.01).The mice in normal control group,TSG groups and huperzine A group had less number of caspase-3 positive cells in cerebral cortex and hippocampus than those in the model group(P<0.01 or P<0.05).The number of caspase-3 positive cells in cerebral cortex and hippocampus of the mice in TSG-treated groups was not significantly different from that of mice in the huperzine A group(P>0.05).Conclusions:(1)TSG can enhance learning and memory abilities of mouse model of Alzheimer’s disease,and improve its hippocampal pathomorphological configurations,these show that TSG has certain therapeutical effect on AD.(2)The mechanisms of TSG on AD might be related to the inhibition of the overexpressions of APP,BACE1,PS-2 and caspase-3 proteins in brain tissues of mice,these proteins are associated with APP abnormal cleavage,so as to reduce the production of amyloid-β,and delay the apoptosis of nerve cells. |
PDF Full Text Request