Study on the Effect of Linggui Zhugan Decoction on Regulating PKA/CREB Pathway and Improving Hippocampal Neuronal Synaptic Damage in Alzheimer's Disease Mice
Study on the Effect of Linggui Zhugan Decoction on Regulating PKA/CREB Pathway and Improving Hippocampal Neuronal Synaptic Damage in Alzheimer's Disease Mice
Objective To observe the effect of Linggui Zhugan decoction on the synaptic damage of hippocampal neurons in Alzheimer's disease(AD)mice,and to explore the possible mechanism.Methods The model of AD were established by bilateral hippocampal injection of Aβ1-42,and they were randomly divided into Linggui Zhugan decoction low,medium,high dose groups(4.29,21.45,42.90g/kg)and Huperzine A group(0.04mg/kg).After administration for 4 weeks,the learning and memory ability of mice was detected by Morris water maze test.The transmission electron microscope was used to observe the synaptic ultrastructure,and the post-synaptic density was measured.The hippocampus pathological changes were compared.The expression of protein kinase A(PKA),cAMP response element binding protein(CREB),and phosphorylation-CREB(p-CREB)protein in hippocampus were detected by Western blot method.Results Compared with AD group,in high,medium and low dose groups,the escape latency of rats were significantly shortened,the times of crossing the original hiding platform were significantly increased,the residence time in the target quadrant were significantly extended,and the thickness of postsynaptic dense matter in hippocampal neurons were significantly increased,the expression of PKA protein and p-CREB/CREB in hippocampus were significantly increased(P＜0.05).Conclusion Linggui Zhugan decoction may reduce the synaptic damage of hippocampal neurons by activating PKA/CREB signaling pathway,and then improve the learning and memory ability of AD mice.
维普
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