Dilinoleoylphosphatidylcholine ameliorates scopolamine-induced impairment of spatial learning and memory by targeting α7 nicotinic ACh receptors

AimsThe present study was conducted to understand the role of 1,2-dilynoleoyl-sn-glycero-3-phosphocholine (DLPhtCho) in cognitive functions.Main methodsTwo-electrode voltage-clamp was made to Xenopus oocytes expressing rat α7 acetylcholine (ACh) receptors. Field excitatory postsynaptic potentials (fEPSPs) were monitored from the CA1 region of rat hippocampal slices. Water maze test was carried out to assess spatial learning and memory for rats.Key findingsIn the oocyte expression system, DLPhtCho at a concentration of 10 µM potentiated ACh-evoked currents to approximately 190% of basal amplitudes 70 min after 10-min treatment. In contrast, 1-stearoyl-2-lynoleoyl-sn-glycero-3-phosphocholine (SLPhtCho), 1-palmitoyl-2-linoleoyl-sn-glycero-3-phosphocholine (PLPhtCho), and 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPhtCho) had no effect on the currents. DLPhtCho (10 µM) enhanced slope of fEPSPs to about 150% of basal levels at 70-min treatment, that is inhibited by α-bungarotoxin, an inhibitor of α7 ACh receptors, while no enhancement was obtained with SLPhtCho, PLPhtCho, or POPhtCho. In the water maze test, oral administration with DLPhtCho (5 mg/kg) significantly shortened the prolonged acquisition latency for rats intraperitoneally injected with scopolamine (1 mg/kg).SignificanceThe results of the present study show that DLPhtCho improves scopolamine-induced learning and memory deficits, possibly by facilitating hippocampal synaptic transmission under the control of α7 ACh receptors. DLPhtCho, therefore, could be developed as a beneficial anti-dementia drug.