Effects Of Bushen Recipe On Social And Learning Behaviors And Synapses Of APP/PS1 Mic

BackgroundAlzheimer’s disease(AD)is the most common type of dementia and there is no cure for it.Social inappropriateness or abnormal social behavior is regarded as one of the neuropsychiatric symptoms and also the presentation due to social cognitive impairment or other cognitive decline,which has been reported at the prodromal stage of AD.Therefore,it could be a possible separate construct for early diagnosis of AD and also a potential outcome in AD clinical trials on account of its correlation with pathological changes in AD.Our team has discovered that AD starts from Shen(Kidney)deficiency.As a result,we suggest reinforcing Shen as the key therapy in the treatment of AD,both in the early stage and throughout the whole process.This research aimed to explore the effects of tonifying Kidney formula(TKF)on social behavior of APP/PS1 mice.Meanwhile,this research also tended to test the effects of TKF on memory and learning ability,neurons and synapses,and beta-amyloid plaque deposition,trying to provide evidence for clinical research in the future.MethodsForty-eight APP/PS1 mice at 3 months of age were randomized into a model group,a positive control group given donepezil(the donepezil group)0.92 mg/kg/d orally,and an experimental group given medium-dose TKF(the TKF(M)group)3.98 g/kg/d orally.In addition,fifteen age-matched C57BL/6J wild-type mice were required as control.Both model group and control group were given a volume of 0.1 ml/10 g/d 0.5%CMC once a day for 8 months.Three-day social nesting and three-chamber test were used to test the effects of TKF on social behavior of APP/PS1 mice.Morris Water Maze was used to test the effects of TKF on memory and learning ability of APP/PS1 mice.Western blot was used to test the expression of synaptic proteins in hippocampus,including PSD-95,Synapsin I,and Synaptophysin.Immunohistochemistry was used to test the expression of NeuN in the CA1 region of the hippocampus,and the plaque deposition composed of Abeta 40 and Abeta 42 respectively in the cortex.ResultsNo distinct abnormality was found in the physical condition examinations,and all the mice through neurological screen test displayed normally in general movements and neurological reflexes.No significant difference was found between groups on the first,second,or third day in social nesting score.In three-chamber test,no significant difference was found between groups in distance moving during the habitation stage.In the sociability stage,aside from the control group which spent more time in zone ① compared with zone ②(P<0.01),the other three groups showed no significant difference in the time spent in zone ① and zone ②.All four groups showed no significant difference in the number of entries to zone ① and zone ②.In preference for social novelty stage,all four groups showed no significant difference in the time spent in zone①and zone②or number of entries to zone①and zone②.All four groups showed that test mice preferred to spend more time interacting with stranger ② than with stranger ①.Compared with the model group,no significant difference was found in the time spent with stranger ①,while the control group spent more time interacting with stranger ②(P=0.004).In the test of Morris Water Maze,no significant difference was found between groups in swimming distance or escape latency during the spatial acquisition stage.No significant difference was found between groups in the number of platform crossings.In the probe trial,the control group spent more time in the target quadrant compared with the model group(P<0.01).The control group showed no significant difference in time spent in each quadrant,while the other three groups spent less time in the target quadrant than in other quadrants,with statistical differences observed.Compared with the model group,the expression of PSD-95(P=0.024)and Synapsin I(P=0.013)in hippocampus were significantly higher in other three groups,while no difference was found between groups in the expression of Synaptophysin.Compared with the model group,the expression of NeuN in CA1 was significantly higher in other three groups(P=0.004).There were significant differences of the positive area of Abeta 40(P=0.01)and Abeta 42(P<0.01)plaque deposition among those four groups.No plaque deposition found in the control group.Compared with the control group,the positive area of Abeta 40 plaque deposition were significantly higher in the donepezil group(P=0.04)and the TKF(M)group(P=0.04);no significant difference was seen between the control group and the model group(P=0.11),nor among the model group,the donepezil group or the TKF(M)group.Compared with the control group,the positive area of Abeta 42 plaque deposition were significantly higher in the model group(P<0.01),the donepezil group(P=0.02),and the TKF(M)group(P=0.04);no significant difference was seen among the model group,the donepezil group or the TKF(M)group.Conclusions(1)To some extent,tonifying Kidney formula is beneficial for improving social function and alleviating memory and learning ability decline in APP/PS1 mice;(2)Tonifying Kidney formula has a protective effect on neurons and synapses in APP/PS1 mice.