关键词: 阿尔茨海默病, 蛋白激酶C, 神经元树突棘形态, 神经元突触功能, 神经元自噬通量

Abstract: By using Western Blot, kinase activity assay, confocolmicroscopy, and electrophysiology recording methods, the synapse toxicity induced by Bryostatin-1 protects Aβ oligomers was studied and its potential mechanisms was investigated. Results showed that in the present of Aβ oligomers, Bryostatin-1 could significantly protect the morphology of dendritic spines, and promote the maturation of dendritic spines. Furthermore, electrophysiology recording result also showed that Aβ oligomers could inhibit mEPSC and Bryostatin-1 could rescue it. The AMPA/NMDA ratio did not change significantly among each group. Western Blot results also showed higher pre- and post-synaptic markers in the present of Bryostatin-1. The mechanisms underlying the protective effect of Bryostatin-1 was investigated. Western Blot results showed that Bryostatin-1 could activate mTOR-S6K1 signal pathway. At last, GFP-RFP-LC3 plasmid was transfected into primary hippocampus neuron culture. Confocolmicroscopy results showed that Aβ oligomers could inhibit the autophagic flux, and Bryostatin-1could promote the autophagic flux in the present of Aβ oligomers. In summary, the present study showed that Bryostatin-1 could activate mTOR-S6K1 signal pathway and then promote autophagic flux in the present of Aβ oligomers, which may be the mechanisms underlying the protective effect of PKC against Aβ oligomers induced synaptic toxicity.

Key words: Alzheimer’s disease, PKC, dendritic spine morphology, synaptic function, autophagic flux