The Impact Of Curcumin On The App/ps1 Double Transgenic Mice Ad7c-ntp, Igf1r, And Chat Expression

ObjectiveAlzheimer's disease is a kind of age-related neurodegenerative disease that is characterized with progressive worsening of memory and cognition. The typical neuropathological lesions include accumulation of Aβresulting in the formation of senile plaques hyperphosphorylated tau resulting in the formation of neurofibrillary tangles neuron and synapse loss, and dysfunction of cholinergic neurons. Now AD deficiency effective early diagnosis and medicine.Latest research indicated that curcumin have neuroprotective 'effect.this discovery become possible to develop safe and effective medicine which prevention and cure of AD.The present study was designed dynamically detect the changes of AD7C-NTP concentration in mouse urine, to integrate immunohistostaining from morphology to observe expression and distribution of AD7C-NTP IGF1R and ChAT in brain. To make use of Western-blot to semiquantitative those index and further investigate the molecule mechanism of the Curcumin prevention and cure of ADMaterial and Methods1. APP/PS1 double transgenic mice (APP/PS1 dtg mice) of 3 months and genetic background and age-matched control littermates were intragastric administration once daily for 3 months. TCM treatment groups (high, medium and low dose) were treated with Curcumin. The positive control group was treated with Rosiglitazone (RSG).2. The spatial learning and memory were tested by step-down test to evaluate the therapeutic effects of Curcumin on cognitive function.3. Using enzyme linked immunosorbent assay to detect AD7C-NTP concentration in mouse urine to investigate the effect of Curcumin on the treatment of Alzheimer's disease.4. To observe the changes of AD7C-NTP,IGF1R and ChAT in hippocampus of APP/PS1 dtg mice using immunohistochemistry and Western-blot methods and to investigate the neuroprotective effect of Curcumin imaginabale mechanism of action. Results1. The effects of Curcumin on ethology learning and memory of APP/PS1 dtg miceIn step-down test of mice,all training phase error number and normal control group of mice (CON) compared to the mouse, the model group (APP/PS1+VEH) error significantly increase in the number of mice (P<0.01). Mouse Beta error number each group compared with CON mouse, significant increase in the number of errors in APP/PS1+VEH mice (P<0.01); APP/PS1+VEH, Curcumin with small-dose group (APP/PS1+Curcumin-L), fewer errors in mouse (P<0.05), the Rosiglitazone group (APP/PS1+RSG), Curcumin high-dose group (APP/PS1+Curcumin-H), Curcumin medium-dose group (APP/PS1+Curcumin-M) error number is significantly reduced (P<0.01). The mice test latency and CON than mice, APP/PS1+VEH latency significantly reduced in mouse (P<0.01), compared with APP/PS1+VEH in mice, APP/PS1+Curcumin-H, APP/PS1+Curcumin-L mice latency increases (P<0.05), the latency increases significantly in APP/PS1+RSG, APP/PS1+Curcumin-M mice (P<0.01).2. Dynamic observation of Curcumin on APP/PS 1 double transgenic mouse urine concentration of AD7C-NTPDynamic comparison of mice AD7C-NTP concentration for each group of mice, results display, Compared with one month time point, the group small rats urine AD7C-NTP concentration rise except APP/PS1+VEH, remaining the group are no statistics differences with treatment before; compared three months treatment with two months treatment, the APP/PS1+RSG,APP/PS1+Curcumin-H,and APP/PS1+Curcumin-M small rats urine AD7C-NTP concentration continues decline and has statistics differences (p<0.01), and APP/PS1+Curcumin-L small rats is no differences (P>0.05).Same time points small rats urine AD7C-NTP concentration changes group between comparison, results display, the group small rats in drug intervention before, APP/PS1+RSG,APP/PS1+Curcumin-H and APP/PS1+Curcumin-M APP/PS1+Curcumin-L compared with APP/PS1+VEH are no statistics differences; treatment three months later APP/PS1+RSG APP/PS1+Curcumin-H APP/PS1+Curcumin-M compared with APP/PS1+VEH small rats urine AD7C-NTP content has decline and has statistics differences (p<0.05,P<0.01). compared with CON, APP/PS1+Curcumin-L small rats urine AD7C-NTP content has rise and has statistics differences (p<0.05) 3.To observe the changes of AD7C-NTP,IGF1R and ChAT in hippocampus of APP/PS1 dtg mice using immunohistochemistry and Western-blot methods and to investigate the neuroprotective effect of Curcumin imaginabale mechanism of action.The results of immunohistochemistry:Compared with CON, the number of APP/PS1+VEH ChAT and IGF1R positive cells in hippocampal CA1 decreased obviously (P<0.01) and the number of AD7C-NTP positive cells increased obviously (P<0.01).the number of APP/PS1-Curcumin-H and APP/PS1+Curcumin-L ChAT and IGF1R positive cells in hippocampal CA1 also decreased (P<0.05) and the number of AD7C-NTP positive cells increased. Compared with APP/PS1+VEH APP/PS1+Curcumin-M and APP/PS1+RSG ChAT and IGF1R positive cells in hippocampal CA1 increased(P<0.05å'ŒP<0.01) and the number of AD7C-NTP positive cells decreased(P>0.05).The motic image analysis system indication that compared with CON, the ChAT and IGF1R cells average gradation of APP/PS1+VEH and APP/PS1+Curcumin-L increased obviously(P<0.01).other group have no different with CON. compared with APP/PS1+VEH, the ChAT and IGF1R cells average gradation of APP/PS1+Curcumin-M and APP/PS1+RSG decreased obviously(P<0.01),the result of AD7C-NTP opposited.The results of Western blot:The result of the expression of each protein matched the result of immunohistochemisty.ConclusionCurcumin can increase the ChAT activity and by regulating IGF1R expression to inhibit AD7C-NTP produce, thus delaying AD purposes of disease progression and improve learning and memory in AD model.