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Abstract:

Objective To explore the effect of DISC1 on the synaptic plasticity，learning and memory ability of APP/PS1 transgenic alzheimer′s disease mice. Methods Western blot was used to detect the expression of DISC1 in the brain tissues between normal people and AD patients. C57BL/6J fetal mouse neurons were cultured in vitro and divided into GFP group，GFP + Aβ group and DISC1 + Aβ group. Laser confocal microscope was used to observe neuron dendritic spines. Two⁃month⁃old C57BL/6J mice were injected into the hippocampus with GFP virus or DISC1⁃overexpressed virus，and then brains were sliced for Aβ treatment. After Aβ treatment，patch clamp technique was used to detect long⁃term potentiation（LTP）of each group to evaluate synaptic plasticity. C57BL/6J mice were divided into WT + GFP group，TG + GFP group，and TG + DISC1 group. Immol/Lunofluorescence stain⁃ ing was used to detect Aβ plaque deposition in the brain and Morris water maze to detect the learning and memory abilities of mice in each group. Results Compared with the none ⁃AD people，the expression of DISC1 in the brain of AD patients decreased（P < 0.05）. Compared with the GFP group，the number of dendritic spines in the GFP + Aβ group decreased，while the number of dendritic spines increased in the DISC1 Aβ group compared to the GFP Aβ group. After Aβ treatment，LTP of mouse brain slices weakened compared with the control group，and with overexpressed DISC1，LTP was enhanced compared with Aβ treatment only. The number of Aβ plaques in the hippocampus of TG + DISC1 group was significantly smaller than that in TG + GFP group（P < 0.05）. In Morris test，the time to find the platform was significantly shorter and the number of times to cross the platform was larger （P < 0.05）. Conclusion Overexpressed DISC1 can protect the synaptic plasticity of APP/PS1 transgenic AD mice and improve its learning ability and memory.

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