Curcumin improves spatial cognitive impairment in APP/PS1 double-transgenic mice through NLRP3/caspase-1/Gasdermi D-axis
Objective To explore the mechanism of curcumin intervention in the progression of Alzheimer's disease(AD)in APP/PS1 double transgenic mice.Methods Seven-month-old male APP/PS1 double transgenic mice were randomly divided into model group and curcumin intervention group,with 6 mice in each group;and 6 mice in the same litter as control.The mice in the curcumin group were intraperitoneally injected with curcumin(200mg/kg)once a day,while the mice in the model group and control group were intraperitoneally injected with the same amount of saline.After 6 consecutive days of injection,the spatial perception and memory ability of the mice were measured by morris water maze.On the 7th day,the rats in each group were sacrificed and the brains were removed for observation of the pathological conditions of brain tissues;TUNEL was used to detect the number of apoptotic cells in hippocampal CA1 and CA3 regions;Western blot was used to detect the protein expressions of Aβ,APP,p-Tau(Ser396),NLRP3,caspase-1,cleaved-caspase-1,Gasdermi D and cleaved-Gasdermi D in hippocampus.Results Curcumin treatment could shorten the latency of AD mice,increase the number of times crossing the platform and the original quadrant retention time;alleviate the inflammatory lesions of hippocampal tissues in AD mice,reduce the apoptosis rate of hippocampal nerve cells,reduce the protein expressions of AD-related proteins Aβ,APP and p-Tau(Ser396)in hippocampus,reduce the protein expressions of pyroptosis-related proteins NLRP3,cleaved-caspase-1 and cleaved-Gasdermi D,and up-regulate the protein expressions of caspase-1 and Gasdermi D.Conclusion Curcumin can improve the spatial cognitive impairment of APP/PS1 double transgenic mice with AD through the NLRP3/caspase-1/Gasdermi D axis,and reduce the hippocampal neuron damage.
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