| Objectives: Explore the protective effect and mechanism of Rosmarinic Acid(Ros-A)on learning and memory impairment,anxiety-like symptoms and other behavioral disorders in APP/PS1 transgenic Alzheimer’s Disease(AD)model mice.Methods: Three months old male APP/PS1 transgenic AD model mice and the Wild Type(WT)mice were given different doses of Ros-A(2.5 mg/kg,5.0 mg/kg,10 mg/kg)or Vehicle(Veh)to explore the improvement effect of Ros-A on behavioral disorders in AD model mice.Morris water maze(MWM)experiment,T-maze food reward experiment,Elevated plus maze(EPM)experiment and Open field test(OFT)were conducted at the age of 8,10 and 12 months to detect the behavior of mice.Golgi staining was used to observe the density changes of neuronal dendritic spines in hippocampus of mice at 10 and 12 months of age.Western blot(WB)was performed to detect the expressions of Bax,Caspase-3,Cytochrome C(Cyt C),Akt,Gsk 3β in the hippocampus of mouse.The expressions of beta III Tubulin protein(Tu J 1)and tubule associated protein 2(MAP 2)in neurons were detected by Immunocytochemistry(ICC)after treatmented with Ros-A(5.0 μmol/L,10.0 μmol/L,20.0 μmol/L)or Veh for 8 days or 21 days.Results:1.The MWM test results of 8 months old experimental mice showed that the time of model group mice spend in the platform quadrant was significantly reduced(P<0.01)compared with the control group,while the situation was significantly increased in the low and the high dose Ros-A treatment group(P<0.05).Compared with the control group,the time in the platform quadrant was significantly reduced in the 10 months old model group(P<0.01),and the time in the platform quadrant was significantly increased after treatment with low(P<0.05),medium(P<0.05)and high(P<0.01)doses of Ros-A.And the 12-month-old model group spent less time in the platform quadrant than the control group(P<0.05).2.The T-maze food reward experiment of 8(P<0.05)and 10(P<0.01)months old experimental mice showed that compared with the control group,the time proportion in the rewarded arm of the model group mice were significantly reduced.While the situation was significantly increased by low(P<0.01),medium(P<0.05)and high(P<0.05)doses of Ros-A in 10 months old.And the time proportion in the rewarded arm of 12 months old model group mice were significantly reduced compared with the control group(P<0.05),which was effectively reversed in both the low and the medium dose Ros-A treatment group(P<0.05).3.The results of EPM test of 8(P<0.05),10(P<0.001)and 12(P<0.05)months old mice showed that the entries made on the closed arms of model group mice were significantly increased compared with control group mice.And the situation was improved effectively in the Ros-A treatment group(P<0.05)in 10 months old.4.The results of the OFT of 10 and 12 months old mice showed that the travel distance of model group mice were significantly reduced compared with that of control group(P<0.01),while the distance was effectively increased in the Ros-A treatment group when they were 10 months old(P<0.05).5.The results of Golgi stain in the hippocampus of 10 months old and 12 months old experimental mice showed that compared with the control group,the density of dendritic spines in the hippocampus of the model group was decreased,while this symptom was improved after the administration of Ros-A.6.The staining results of ICC showed that Ros-A treatment upgraded the growth state of neurons.7.WB result of protein in the hippocampus of 10 months old mice showed that there was no significant difference in the expression of Bax in the model group compared with the control group,while the expression of Caspase-3(P<0.05),Cyt C(P<0.001),Akt(P<0.05)and Gsk 3β(P<0.05)were significantly increased.The expression of caspase-3(P<0.05),Cyt C(P<0.001),Akt(P<0.05)in hippocampus of the low-dose Ros-A treatment group were significantly reduced,while no significant difference was found in expression of Bax and Gsk 3β in those two groups.And the expression of Caspase-3(P<0.01),Cyt C(P<0.001),Akt(P<0.01)and Gsk 3β(P<0.05)were significantly reduced in the medium-dose Ros-A treatment group compared with the model group,while there was no significant difference in expression of Bax in those two groups.Compared with the model group,the expression of Caspase-3(P<0.05),Cyt C(P<0.001)and Akt(P<0.01)were significantly reduced in the high-dose Ros-A treatment group,but no significant differences were found in expression of Bax and Gsk 3β in those two groups.The expression of Bax(P<0.05),Caspase-3(P<0.05)and Akt(P<0.01)were significantly increased in the 12 months old model group compared with the control group,while no significant difference was found in the expression of Cyt C and Gsk 3β in those two groups.And compared with the model group the high-dose Ros-A treatment effectively reduced the level of Caspase-3 in hippocampus(P<0.05).Conclusion(s): Ros-A administration can improve the behavior disorder of AD model mice.And its mechanism may be related to upgraded the growth state of neurons,increasing the density of dendrite spines and preventing the abnormal activation of Bax/Caspase-3/GSK 3β in the hippocampus of mouse brain. |
PDF Full Text Request