Curcumin On Synaptic Shank1 Protein Involved In Ad Mice, The Influence Of Psd95 Expression

ObjectiveAlzheimer’s disease (AD) is an age-related progressive neurodegenerative disease characterized by insidious cognitive decline and memory dysfunction. The distinctive neuropathological lesions of AD include extensive loss of neuron and synapse, extra-cellular senile plaques and intracellular neurofibrillary tangles. Early in AD patients is not easy to be found, onset hidden, slow progression of symptoms, deterioration of the memory step by step, cognitive dysfunction, personality change and so on, and for progressive irreversibility. But the present treatment most can only improve and relieve symptoms, cannot fundamentally reverse AD pathology process.This experiment was designed to observe and quantify the effects of curcumin on the ability of learning and memory, the number and form of synapse, expression of Shank1, PSD95of APP/PS1double transgenic mice, to investigate the protective mechanism of curcumin on neuronal survival.Material and Methods1APP/PS1double transgenic mice(APP/PS1dtg mice) of3months and genetic background and age-matched control littermates were intragastric administration once daily for6months. The all treatment groups(high, medium and low dose) were treated with curcumin. The positive control group was treated with Rosiglitazone(RSG).2The spatial learning and memory were tested by Morris water maze to evaluate the therapeutic effects of curcumin on cognitive function.3To observe the changes of neurons and synapses in hippocampus CA1area of APP/PS1dtg mice using electronic microscope and to evaluate the therapeutic effect of curcumin on synapse structures and function.4To observe the changes of Shankl and PSD95in hippocampus CA1area of APP/PS1dtg mice before and after curcumin treatment using immunohistochemistry and Western-blot methods.5Statistical analysis:The experimental data are pressed as means±standard deviation said,using the one-way ANOVA statistical method, P<0.05was considered statistically significant.Results1Effects of curcumin on ethology, special learning and memory of APP/PS1dtg miceIn probe trial of Morris water maze, compared with the normal control, the frequency of platform site transversing was significantly decreased (P<0.05), the swimming time in target quadrant of APP/PS1dtg mice was significantly decreased (P<0.01)too, the swimming time in target quadrant of APP/PS1+curcumin-L group was significantly shortened (P<0.05). Compared with APP/PS1dtg mice, the transversing frequency of all the treatment group mice was significantly augmented (P<0.05), the swimming time in target quadrant was extended (P<0.05).2Effects of Curcumin on numbers and form of neurons and synapse of APP/PS1dtg mice.The structures of hippocampal neurons and neuropils were normal in normal control group. Neurons of hippocampal CA1area in APP/PS1dtg mice showed varying degrees of degenerative changes, including neuronal shrinkage, markedly increased cytoplasmic lipofuscin and lipid droplets, irregular nuclei shape, some nuclear chromatin condensation; cytoplasmic lipofuscin and lipid droplets increase, dilation of Golgi vesicles, discretion of rough endoplasmic reticulum, depolymerization of polyribosomes, some mitochondria degeneration. In neuropil it is seen that myelin degeneration, reduced synapses and structural abnormalities of synapses and increased aggregation of synaptic vesicles. Curcumin can increase synapses and make these changes improved to varying degrees.3Effects of curcumin on the expression of Shank1in the hippocampus of APP/PS1dtg mice Results of immunohistochemistry:Compared with CON group mice, Shankl positive cells of hippocampus CA1area of APP/PS1dtg mice were markedly decreased (P<0.05). Compared with APP/PS1dtg mice, Shank1positive cells of hippocampus CA1area of APP/PS1+RSG group and all the groups of curcumin were markedly increased(P<0.05),The results of Western blot:The results of the expression of Shank1corresponded to the above results.4Effects of curcumin on the expression of PSD95in the hippocampus of APP/PS1dtg mice.Results of immunohistochemistry:Compared with CON group mice, PSD95positive cells of hippocampus CA1area of APP/PS1dtg mice were markedly decreased (P<0.05). Compared with APP/PS1dtg mice, PSD95positive cells of hippocampus CA1area of APP/PS1+RSG group and all the groups of curcumin were markedly increased(P<0.05).The results of Western blot:The results of the expression of PSD95corresponded to the above results.ConclusionCurcumin can improve the learning and memory ability of APP/PS1double transgenic mice, protection synaptic, effect the expression of Shank1and PSD95, play the protective mechanism of curcumin on neuronal survival.