P3‐060: oleuropein reversed age‐dependent impairment to sustain long‐term potentiation (ltp) in perforant path‐dentate gyrus synapses and increased microtubule‐associated protein 2 level

Oleuropein is a glycosylated secoiridoid, a type of phenolic bitter compound found in green olives, olive leaves and herbal medicines. Numerous reports have shown that Oleuropein administration improved cognitive deterioration, the exact physiological mechanism is not yet elucidated. In the previous study, we found that Oleuropein significantly facilitated long term potentiation (LTP) induction and maintenance in perforant path-dentate gyrus synapses in rats. In the present study, we investigated the effect of Oleuropein on synaptic LTP in Middle-aged rats both in vivo and in vitro, and also synaptic plasticity proteins changes, include synapsin I, Growth Associated protein 43(GAP43), and microtubule-associated protein 2 (MAP-2). For LTP recording invivo, an outer guide cannula, a monopolar recording electrode, and a bipolar stimulating electrode were implanted in the skull and extracellular recording technique was used to record the population spike (PS) in dentate gyrus. Drugs or vehicle injections were delivered via a cannula in the lateral cerebral ventricle. LTP at Schaeffer collateral-CA1 hippocampal synapses was recorded in vitro, field excitatory postsynaptic potentials (fEPSPs) were recorded from the stratum radiatum layer of the CA1 area in response to electrical stimulation of Schaeffer collateral afferents. LTP was induced by high-frequency stimulation (HFS, 10 trains, 100 Hz), and responses were monitored for 1 h. Protein expression was assessed by western blotting. All data was expressed as mean percentage of mean baseline. PS amplitude of middle-aged rats was increased to 154% ± 16 % (n=6, p<0.01) after HFS. Oleuropein 10, 100 nmol·L-1 significantly increased PS amplitude to 178 % ± 8 % (n=6, p<0.01) and 249 % ± 16 % (n=6, p<0.01) respectively, but not in rats acute hippocampus slices in vitro. Western blotting results showed that MAP2 expression level in hippocampus was significantly increased after OE administration (n=5, p<0.01 compared with MCI rats) but no change in GAPA43 and synapsin I expression. Oleuropein increased PS amplitude and LTP induction dose-dependently in vivo, but not in vitro, the metabolites of Oleuropein may the ultimate acting bioactive components. Oleuropein significantly increased MAP2 expression, which may one of the mechanisms that underlie LTP induction. (NSFC 81373418).