Bryostatin-1 protects synapse morphology and function against Aβ toxicity
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 Bryosta-tin-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 in-vestigated.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 au-tophagic 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.
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