Effects Of Curcumin On Aβ And ADDLs In APPswe / PS1dE9 Double Transgenic Mice

ObjectiveAlzheimer’s disease (AD) is the most common type dementia, with the rise of global incidence, it brings serious burden for the family and the society, so seeking for the prevention and treatment targets for AD is urgently needed. Beta amyloid (Aβ) hypothesis is one of the most recognized pathogenesis of AD, the hypothesis suggests that Aβ is the main toxic substance, which is hydrolyzing from amyloid precursor protein(APP), it can easily assembled into Aβ oligomers, that is Aβ derived diffusible ligands (ADDLs), which has severer nerve toxicity. They release and combine to the specific area, influence the structure and function of synapses, which leads to memory impairment. Recently, there is no effective drug treatment for AD, curcumin is a monomer of traditional Chinese medicine, which has positive pharmacological effects on multi-system disease, and its application to AD is of popular attention. APPswe/PS1dE9 double transgenic mice is the most accepted AD animal models, it can produce a large number of Aβ and ADDLs in relatively short period of time in brain, which are similar pathological changes in AD.Therefore this paper is to observe the effects of curcumin on APPswe/PS1dE9 double transgenic mice after intragastric administration for 6 months. Using Morris water maze to evaluate cognitive function, and to observe the changes of Aβ40, Aβ42 and ADDLs in brain, providing experimental basis for the TCM treatment on AD.Material and methods3-month old APPswe/PS1dE9 dtg mice were randomly divided into model group, rosiglitazone group (10 mg/kg/d) and curcumin high (400 mg/kg/d), medium (200 mg/kg/d) and low dose group (100 mg/kg/d),15 per group.Age-matched and the same genetic background C57BL/6J mice were choosed as normal Model group. Medication was given by intragastric administration once a day for 6 months.After treatment for 6 months, Morris water maze was used to test learning and memory ability of all the mice, records of the swimming time and frequency of transversing cross the platform. Then using immunohistochemistry and Western blot methods to observe the number of positive cells and the distribution and expression of Aβ40, Aβ42and ADDLs in brain.ResultsMorris water maze in mice behavior test results found that curcumin decreased the swimming time, and increased the frequency of transversing cross the platform, it suggested that curcumin have an improvement effect on the spatial learning and memory ability of AD model mice. Results of Immunohistochemical staining and Western blot methods both observed that compared with normal group, the positive cell counts and protein expression of Aβ40, Aβ42 and ADDLs significantly increased (P<0.01) in brain. Other groups were compared to model group, from the results of Aβ40, the number of positive cells in curcumin high and medium dose group was decreased(P<0.05), as well as the protein expression was significantly lower(P <0.01), it suggested that high and medium dose of curcumin could significantly reduce Aβ40. All doses of curcumin could lower the positive cell numbers and protein expression of Aβ42 (P < 0.05), the curcumin medium dose group was more obvious (P<0.01).From the results of ADDLs showed that all doses of curcumin could decrease the positive cells (P<0.01),but western blot showed only curcumin high and medium dose group decreased the protein expression (P<0.05), there is no difference incurcumin low dose group.ConclusionsAdministration with Curcumin for 6 months can improve learning and memory ability of APPswe/PS1dE9 double transgenic mice, as well as reduce the expression of Aβ40, Aβ42 and ADDLs in hippocampus, play a role of neuroprotection by influencing Aβ cascade reaction.