Dilinoleoylphosphatidylcholine ameliorates scopolamine-induced impairment of spatial learning and memory by targeting alpha7 nicotinic ACh receptors.
OBJECTIVE
The present study was conducted to understand the role of 1,2-dilynoleoyl-sn-glycero-3-phosphocholine (DLPhtCho) in cognitive functions.


METHODS
Two-electrode voltage-clamp was made to Xenopus oocytes expressing rat alpha7 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.


RESULTS
In the oocyte expression system, DLPhtCho at a concentration of 10 microM 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 microM) enhanced slope of fEPSPs to about 150% of basal levels at 70-min treatment, that is inhibited by alpha-bungarotoxin, an inhibitor of alpha7 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).


CONCLUSIONS
The 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 alpha7 ACh receptors. DLPhtCho, therefore, could be developed as a beneficial anti-dementia drug.
Yaguchi
Takahiro
T
Division of Bioinformation, Department of Physiology, Hyogo College of Medicine, Nishinomiya, Japan.
Nagata
Tetsu
T
Nishizaki
Tomoyuki
T
D000818:Animals; D018680:Cholinergic Antagonists / Q000378:metabolism / Q000494:pharmacology; D008297:Male; D018782:Maze Learning / Q000187:drug effects*; D008568:Memory / Q000187:drug effects*; D009865:Oocytes / Q000166:cytology / Q000502:physiology; D018408:Patch-Clamp Techniques; D010713:Phosphatidylcholines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D011978:Receptors, Nicotinic / Q000378:metabolism*; D012601:Scopolamine / Q000378:metabolism / Q000494:pharmacology; D013037:Spatial Behavior / Q000187:drug effects; D014982:Xenopus laevis; D064569:alpha7 Nicotinic Acetylcholine Receptor
D018680:Cholinergic Antagonists; C579165:Chrna7 protein, rat; D010713:Phosphatidylcholines; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor; C002448:1,2-linoleoylphosphatidylcholine; D012601:Scopolamine