1-palmitoyl-2-oleoylphosphatidylcholine and Memory-Disorders

The present study investigated the effects of 1,2-dilinoleoyl-sn-glycero-3-phosphocholine (DL-PC) and 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (PO-PC) on depression-related behaviors and spatial memory impairment in mice subjected to restraint stress. The immobility time in forced-swim and tail-suspension tests for mice subjected to restraint stress was significantly longer than that for nonstressed control mice, and oral coadministration of DL-PC and PO-PC (DL-/PO-PC; DL-PC : PO-PC=1 : 1) shortened the prolonged immobility time in a dose (0.1-5 mg/kg)-dependent manner. In the water maze test, the retention latency for stressed mice was significantly longer than that for control mice and DL-/PO-PC (1 mg/kg, per os) reversed the prolonged latency to control levels. Phosphorylation of Akt and glycogen synthase kinase 3β (GSK-3β) in the hypothalamus of stressed mice was significantly reduced compared with that for control mice, and DL-/PO-PC (1 mg/kg, per os) recovered the reduced phosphorylation of Akt and GSK-3β. The results of the present study indicate that DL-/PO-PC has the potential to ameliorate stress-induced depression-related behaviors and memory impairment, possibly by activating Akt and inhibiting GSK-3β.

Topics: Animals; Depressive Disorder; Disease Models, Animal; Glycogen Synthase Kinase 3; Glycogen Synthase Kinase 3 beta; Hypothalamus; Male; Maze Learning; Memory Disorders; Mice, Inbred C57BL; Motor Activity; Neuropsychological Tests; Phosphatidylcholines; Phosphorylation; Proto-Oncogene Proteins c-akt; Psychotropic Drugs; Restraint, Physical; Spatial Memory; Stress, Psychological

In the water maze test, oral administration with 1,2-dilynoleoyl-sn-glycero-3-phosphocholine (DLPhtCho)(5 mg/kg) alone or DLPhtCho (5 mg/kg) plus 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPhtCho)(5 mg/kg) significantly shortened the prolonged acquisition latency for rats intraperitoneally injected with scopolamine, with more efficient effect than (POPhtCho)(5 mg/kg) alone, arachidonic acid (AA)(5 mg/kg) alone, docosahexaenoic acid (DHA)(5 mg/kg) alone, or 1-palmitoyl-2-linoleil-sn-glycero-3-phosphoserine (PLPhtSer)(5 mg/kg) alone. POPhtCho (5 mg/kg) alone or DLPhtCho (5 mg/kg) plus POPhtCho (5 mg/kg) also significantly shortened the prolonged retention latency for rats intraperitoneally injected with scopolamine, but otherwise no significant effect was obtained with DLPhtCho (5 mg/kg) alone, AA (5 mg/kg) alone, DHA (5 mg/kg) alone, or PLPhtSer (5 mg/kg) alone. Oral co-administration with DLPhtCho (5 mg/kg) and POPhtCho (5 mg/kg) significantly shortened the acquisition latency for rats untreated with scopolamine as compared with the latency for administration with polyethylene glycol (PEG), DLPhtCho alone at doses of 5 and 10 mg/kg, or POPhtCho alone at doses of 5 and 10 mg/kg, while no efficient effect on the retention latency was obtained. To assess the effect of DLPhtCho and POPhtCho on cognitive functions for humans, Mini Mental State Examination (MMSE) test was performed in subjects with cognitive disorders (the average MMSE score, 15). Oral co-intake with DLPhtCho (50 mg) and POPhtCho (45 mg) once after breakfast everyday raised the score to over 20, corresponding to normal cognitive functions, throughout 5 months after intake, and the increase in the score was significantly greater than that for oral intake with DLPhtCho (100 mg/day) alone or POPhtCho (90 mg/kg) alone. Taken together, the results of the present study show that co-intake with DLPhtCho and POPhtCho could enhance learning and memory ability and improve cognitive disorders for both the animals and humans with a promising efficacy.

Topics: Aged; Aged, 80 and over; Animals; Cognition Disorders; Disease Models, Animal; Drug Combinations; Female; Humans; Male; Maze Learning; Memory Disorders; Middle Aged; Nootropic Agents; Phosphatidylcholines; Rats; Rats, Wistar; Scopolamine