| Alzheimer’s disease (AD) is a kind of neurodegenerative diseases that is characterized by loss of gradual onset of aggravating gradually memory. AD pathological changes mainly happens in the brain cortex and brain regions,①Extracellular space composed of β-amyloid (Aβ) precipitation Senile plaques (SPs);②Highly phosphorylated tau protein made of neurofibrillary tangles (NFTs) in cells;③In addition, accompanied by loss of synapses, swelling and death of neurons and the dysfunction of cholinergic neurons with AD.2012China health statistics annual review; display for dementia mortality rates on the rising year by year. At present, AD only to take measure with symptomatic, and lack of effective methods of early diagnosis and treatment. Research at home and abroad, traditional Chinese medicine monomer of curcumin has good nerve protective effect on neurodegenerative disease such as pharmacological effects of AD, according by anti-inflammatory, antioxidant, inhibition of abnormal proteins accumulate, and opened the door for AD to drug research.This study aims to test the APP/PS1double transgenic mice as AD mice in urine Alzheimer-associated neuronal thread protein (AD7C-NTP), observation of dynamic effect of curcumin on urine concentration of AD7C-NTP in AD mice, and combining behavioral detection platform experiment, to observe curcumin influence on9months AD learning and memory in mice, and by immunohistochemical study from the aspects of morphology observation within9months of age small mouse AD7C-NTP, insulin-like growth factor1receptor (IGFIR) and choline acetyltransferase (ChAT) the expression and distribution of ChAT. Using Western-blot method, the above mentioned indexes semi-quantitative observation to further explore the molecular mechanism of nerve protective effect of curcumm.Material and Methods1.3months APP/PS1double transgenic mice (AD mice) and C57BL/6J mice with genetic background and age-matched littermates as AD mice control were as experimental subjects, each group12. The positive control group was treated with Rosiglitazone. Traditional Chinese medicine large, medium and small dose group were given curcumin gavage; rosiglitazone rosiglitazone given orally; model group and normal control group received an equal volume solvent gavage once daily gavage6months.2. Platform was application to test AD mice learning memory and memory capacity, to evaluation of curcumin influence on9months AD mice cognitive ability.3. There were applying the method of enzyme-linked immunosorbent (ELISA) to detect the content of mice AD7C-NTP, and observation of curcumin for9months AD mice urine dynamic effect of AD7C-NTP.4. To observe the change of the expression with IGF1R, ChAT and AD7C-NTP in hippocampus of the AD mice to curcumin treatment6months, using immunohistochemistry and Western-blot methods, exploring possible mechanisms of curcumin on neural protection.Results1. Dynamic effect of curcumin on urine concentration of AD7C-NTP in AD miceThe comparison of AD7C-NTP of each group was compared at the same time point, the concentration of model group is higher than control group(P<0.05); the concentration of other groups is lower than model group. The comparison of high curcumin dose group with4months treatment, has no statistical difference compared with model group. The AD7C-NTP comcentration of each group of wad elevated with the age growth, and all concentration of the treatment group was lower than model group at the same time period. With the treatment of4,5and6month, the concentrationof control group has significant difference with the treatment group (P<0.01). There have no statistical difference between all the group with the treatment of6months compared with5months.2. The influence of curcumin on learning and memory in AD miceEach AD mice training error number and the number of test phase error:Compared with the control group mice model group obviously increase the number of errors in mice (P<0.01), the other groups AD mice were no significant differences (P>0.05); other groups compared with model group mice, mice error number decreased significantly (P<0.01). Groups of mice the incubation period of time:Compared with control group mice, time of the model mice decreased significantly (P<0.01), the other groups AD mice were no significant differences (P>0.05); compared with the model mice, curcumin moderate dose group mice have no obvious difference, other groups latency time in mice increased (P<0.05).3. Effect of curcumin on AD mice IGF1R etc.The results of AD mouse hippocampal CA1area immunohistochemical staining: Compared with the control group mice, IGF1R positive cells of the model group mice was significantly reduced (P<0.01); compared with model group mice, IGF1R positive cells of rosiglitazone and curcumin moderate dose group mice was significantly increased (P<0.01). Compared with the control group mice, ChAT positive cells of the model group mice was significantly reduced (P<0.01); compared with model group mice, positive cells of curcumin moderate dose group mice was increased (P<0.05), and positive cells of curcumin high dose group mice was significantly increased (P<0.01). Compared with control group mice, AD7C-NTP positive cells of the model mice was significantly increased (P<0.01); compared with model group mice, AD7C-NTP positive cells of rosiglitazone, curcumin high and moderate dose group was significantly reduced (P<0.05).The results of AD mouse hippocampal Western blot:protein expression results of IGF1R, ChAT and AD7C-NTP are in conformity with immunohistochenmistry.ConclusionCurcumin can improve learning of AD mice, and reducing the AD mice hippocampus and urine AD7C-NTP level, and increasing ChAT and IGF1R protein expression of AD mice hippocampus, to delay of alzheimer disease progression. |
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