1-palmitoyl-2-oleoylphosphatidylcholine and Cognition-Disorders

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

1-Palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPhtCho) (1 microM) enhanced long-term depression (LTD), a synaptic plasticity relevant to learning and memory, in the CA1 region of rat hippocampal slices, where expression of the alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor subunit GluR1 on the plasma membrane was decreased. In the water maze test, oral administration with POPhtCho (5 mg/kg) significantly shortened the prolonged retention latency for rats intraperitoneally injected with scopolamine (1 mg/kg), while the acquisition latency was not affected. For humans with mild cognitive impairment and dementia (average of Mini Mental State Examination score, 18), oral intake with POPhtCho (300 mg/day, once after breakfast) everyday raised the score to over 20, corresponding to normal cognitive functions, throughout 6 months after intake. The results of the present study, thus, indicate that POPhtCho could ameliorate cognitive disorders, possibly by enhancing LTD.

Topics: Aged; Aged, 80 and over; Animals; Central Nervous System Agents; Cognition Disorders; Dementia; Excitatory Postsynaptic Potentials; Female; Hippocampus; Humans; In Vitro Techniques; Long-Term Synaptic Depression; Male; Maze Learning; Middle Aged; Phosphatidylcholines; Psychiatric Status Rating Scales; Rats; Rats, Wistar; Receptors, AMPA